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Takata K, Yugami M, Karata S, Karasugi T, Uehara Y, Masuda T, Nakamura T, Tokunaga T, Hisanaga S, Sugimoto K, Yonemitsu R, Ideo K, Fukuma Y, Uragami M, Arima T, Kawakami J, Maeda K, Yoshimura N, Matsunaga H, Kai Y, Tanimura S, Shimada M, Shibata Y, Tateyama M, Takata S, Goshogawa H, Yumoto M, Takashima Y, Inoue S, Ueno S, Kubo R, Tajiri R, Tian X, Honma F, Kawamura Y, Miyamoto T. Plates made from magnesium alloy with a long period stacking ordered structure promote bone formation in a rabbit fracture model. Sci Rep 2025; 15:12210. [PMID: 40204858 PMCID: PMC11982537 DOI: 10.1038/s41598-025-96853-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 04/01/2025] [Indexed: 04/11/2025] Open
Abstract
Operative treatment is an option for fractures when the fracture is unstable or the patient wishes to return early to daily life or social activities. Metal plates such as titanium and stainless steel are often used in fracture surgery, but the metal plate lacks bone-healing activity and is not bioabsorbable, requiring a second surgery to remove it after bone union. Here we show that a magnesium (Mg) plate made from an alloy of yttrium, zinc, and aluminum with magnesium as the main component in a long-period stacking ordered structure promotes bone formation in a rabbit tibia fracture model and is also bioabsorbable. We show that the Mg plate significantly promoted bone and callus formation compared to a titanium plate in the rabbit tibia fracture model. Moreover, the Mg plate was mostly bioabsorbed once bone union was achieved, but rabbits showed no evidence of biotoxic effects, such as weight loss or increased blood magnesium levels. We also demonstrate that treatment with exogenous magnesium significantly enhanced calcium deposition in an in vitro osteoblast culture system. Magnesium is an essential element, and its radiolucency facilitates observation of the fracture site during Mg plate fixation, while its lack of magnetic properties allows its use in patients who require MRI scans. Accordingly, we propose that a use of a Mg plate could be beneficial in treating bone fracture.
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Affiliation(s)
- Kosei Takata
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Masaki Yugami
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Soichiro Karata
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Tatsuki Karasugi
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yusuke Uehara
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Tetsuro Masuda
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Takayuki Nakamura
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Takuya Tokunaga
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Satoshi Hisanaga
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Kazuki Sugimoto
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Ryuji Yonemitsu
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Katsumasa Ideo
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yuko Fukuma
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Masaru Uragami
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Takahiro Arima
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Jyunki Kawakami
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Kazuya Maeda
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Naoto Yoshimura
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hideto Matsunaga
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yuki Kai
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shuntaro Tanimura
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Masaki Shimada
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yuto Shibata
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Makoto Tateyama
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shu Takata
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hikaru Goshogawa
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Mizuho Yumoto
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yusuke Takashima
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shinichi Inoue
- Magnesium Research Center & Department of Material Science, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-85565, Japan
| | - Syotaro Ueno
- Magnesium Research Center & Department of Material Science, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-85565, Japan
| | - Ryuta Kubo
- Department of Oral and Maxillofacial Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Rui Tajiri
- Department of Oral and Maxillofacial Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Xiao Tian
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Fuka Honma
- Department of Oral and Maxillofacial Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yoshihito Kawamura
- Magnesium Research Center & Department of Material Science, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-85565, Japan
| | - Takeshi Miyamoto
- Faculty of Life Sciences, Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
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Kawaguchi H. Assessment of evidence for the off-label application of osteoanabolic drugs in fracture healing and spinal fusion. J Bone Miner Metab 2025; 43:57-60. [PMID: 39964554 DOI: 10.1007/s00774-025-01589-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Accepted: 01/27/2025] [Indexed: 04/13/2025]
Abstract
Osteoanabolic drugs are sometimes prescribed off-label for "fracture healing and spinal fusion." This study examines the scientific validity of such practices by analyzing existing clinical reports. The purported bone union-promoting effect of teriparatide in fracture cases has been refuted in clinical trials. While teriparatide shows efficacy in accelerating spinal fusion after surgery for patients with osteoporosis, there is no scientific justification for its off-label use in patients without osteoporosis. For osteoporosis patients, no clear evidence suggests that teriparatide is superior to antiresorptive drugs, making the rationale for switching from antiresorptive drugs to teriparatide weak. The efficacy in postoperative spinal fusion may primarily be attributed to systemic improvements in bone quality and quantity, enhancing the mechanical engagement of implants. The clinical evidence for the off-label use of romosozumab, another osteoanabolic drug, in fracture healing and spinal fusion is insufficient to support its efficacy. In conclusion, osteoanabolic drugs, like antiresorptive drugs, primarily have systemic functions in osteoporosis patients, with limited evidence supporting their role in promoting localized bone formation in fractures or spinal fusions.
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Stumpf U, Schmidmaier R, Taipaleenmäki H, Böcker W, Kurth A, Hesse E. [Influencing fracture healing by specific osteoporosis medications]. Z Rheumatol 2025; 84:107-112. [PMID: 39806104 DOI: 10.1007/s00393-024-01610-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/04/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Osteoporosis is a widespread disease defined by a reduction in bone mass and structure, thereby increasing the risk of fragility fractures. Treatment typically involves specific medications, which either inhibit bone resorption (antiresorptive) or stimulate bone formation (anabolic) and may potentially influence the healing of osteoporotic fractures. On the other hand, metabolic disorders, immune system dysfunctions or circulatory problems can impair fracture healing. Therefore, the targeted use of osteoporosis medications could be a strategy to promote the healing of impaired fractures. OBJECTIVE The aim of this study is to provide a current overview of the effects of osteoporosis medications approved in Germany on fracture healing. The focus is on the potential influence of these medications in the context of osteoporosis treatment. Additionally, the current state of research is examined to explore to what extent the targeted use of these medications could improve fracture healing. MATERIAL AND METHODS A literature search was conducted in the PubMed database using topic-specific keywords. Preclinical studies, clinical trials, review articles and meta-analyses were considered to present the current scientific knowledge with clinical relevance. RESULTS Preclinical and clinical studies suggest that specific osteoporosis medications do not have a clinically relevant negative impact on the healing of fragility fractures. Osteoanabolic substances even tend to have a positive effect on fracture healing in both normal and impaired healing processes; however, the available studies are limited and none of the medications have been approved for this specific use. DISCUSSION Osteoporosis medications with antiresorptive or osteoanabolic effects are primarily used to treat osteoporosis, especially after fragility fractures, to reduce the risk of further fractures. There is no clinically relevant impairment of fracture healing due to these medications. Further studies would be required to obtain approval for these medications specifically to improve fracture healing.
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Affiliation(s)
- Ulla Stumpf
- Klinik für Orthopädie und Unfallchirurgie, LMU Klinikum, LMU München, München, Deutschland
- Osteologisches Schwerpunktzentrum DVO (OSZ), Bayerisches Osteoporose-Zentrum, LMU Klinikum, LMU München, München, Deutschland
- Muskuloskelettales Universitätszentrum München, LMU Klinikum, LMU München, Fraunhoferstr. 20, 82152, Planegg-Martinsried, Deutschland
| | - Ralf Schmidmaier
- Medizinische Klinik und Poliklinik IV, LMU Klinikum, LMU München, München, Deutschland
- Osteologisches Schwerpunktzentrum DVO (OSZ), Bayerisches Osteoporose-Zentrum, LMU Klinikum, LMU München, München, Deutschland
| | - Hanna Taipaleenmäki
- Institut für Muskuloskelettale Medizin, LMU Klinikum, LMU München, München, Deutschland
- Osteologisches Schwerpunktzentrum DVO (OSZ), Bayerisches Osteoporose-Zentrum, LMU Klinikum, LMU München, München, Deutschland
- Muskuloskelettales Universitätszentrum München, LMU Klinikum, LMU München, Fraunhoferstr. 20, 82152, Planegg-Martinsried, Deutschland
| | - Wolfgang Böcker
- Klinik für Orthopädie und Unfallchirurgie, LMU Klinikum, LMU München, München, Deutschland
- Osteologisches Schwerpunktzentrum DVO (OSZ), Bayerisches Osteoporose-Zentrum, LMU Klinikum, LMU München, München, Deutschland
- Muskuloskelettales Universitätszentrum München, LMU Klinikum, LMU München, Fraunhoferstr. 20, 82152, Planegg-Martinsried, Deutschland
| | - Andreas Kurth
- Orthopädische Privatpraxis Dres. Baron & Kollegen, Frankfurt am Main, Deutschland
| | - Eric Hesse
- Institut für Muskuloskelettale Medizin, LMU Klinikum, LMU München, München, Deutschland.
- Osteologisches Schwerpunktzentrum DVO (OSZ), Bayerisches Osteoporose-Zentrum, LMU Klinikum, LMU München, München, Deutschland.
- Muskuloskelettales Universitätszentrum München, LMU Klinikum, LMU München, Fraunhoferstr. 20, 82152, Planegg-Martinsried, Deutschland.
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Jacob G, Shimomura K, Nakamura N. Biologic therapies in stress fractures: Current concepts. J ISAKOS 2024; 9:100256. [PMID: 38631518 DOI: 10.1016/j.jisako.2024.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 04/08/2024] [Accepted: 04/10/2024] [Indexed: 04/19/2024]
Abstract
Stress fractures, a common overuse injury in physically active individuals, present a significant challenge for athletes and military personnel. Patients who sustain stress fractures have demanding training regimes where periods of rest and immobilisation have unacceptable negative consequences on sports goals and finances. Aside from being an overuse injury, there are various contributing risk factors that put certain individuals at risk of a stress fracture. The main two being nutritional deficiencies and hormonal variations, which have significant effects on bone metabolism and turnover. Historically, treatment of stress fractures focused on conservative strategies such as rest and immobilisation. Calcium and vitamin D deficiencies have been closely linked to stress fractures and so over time supplementation has also played a role in treatment. With the introduction of biologics into orthopaedics, newer treatment strategies have been applied to accelerate fracture healing and perhaps improve fracture callus quality. If such therapies can reduce time spent away from sport and activity, it would be ideal for treating stress fractures. This article aims to offer insights into the evolving landscape of stress fracture management. It investigates the pre-clinical evidence and available published clinical applications. Though fracture healing is well understood, the role of biologics for fracture healing is still indeterminate. Available literature for the use of biologic therapies in stress fractures are restricted and most reports have used biologics as a supplement to surgical fixation in subjects in studies that lack control groups. Randomised control trials have been proposed and registered by a few groups, with results awaited. Assessing individuals for risk factors, addressing hormonal imbalances and nutritional deficiencies seems like an effective approach to addressing the burden of stress fractures. We await better designed trials and studies to accurately determine the clinical benefit of adding biologics to the management of these injuries.
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Affiliation(s)
- George Jacob
- Department of Orthopaedic Surgery, Lakeshore Hospital, Cochin, India
| | - Kazunori Shimomura
- Department of Rehabilitation, Kansai University of Welfare Sciences, Osaka, Japan; Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Norimasa Nakamura
- Institute for Medical Science in Sports, Osaka Health Science University, Osaka, Japan; Global Centre for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
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Novikov D, Kelley MG, Kain MS, Tornetta P. Low Rate of Teriparatide Supplementation for the Treatment of Osteoporotic Pelvic Fractures in Elderly Females. Geriatr Orthop Surg Rehabil 2024; 15:21514593241296396. [PMID: 39584187 PMCID: PMC11585054 DOI: 10.1177/21514593241296396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 09/11/2024] [Accepted: 10/15/2024] [Indexed: 11/26/2024] Open
Abstract
Background Osteoporotic pelvic fractures in the elderly lead to pain and immobility resulting in decreased quality of life and worsening frailty. Teriparatide has been shown to shorten time to fracture union, diminish pain, and improve mobilization. At our hospital, this medication is prescribed by an outpatient endocrinologist or geriatrician. We hypothesize that elderly female patients sustaining low energy lateral compression (LC) pelvic fractures are not given Teriparatide. This study reports rates of successful Teriparatide initiation and looks for areas of improvement. Materials and Methods A retrospective chart review of stable LC pelvic fractures admitted to a single urban academic level 1 trauma center from January 2012 to February 2021 was conducted. Females over 60 years old with stable LC pelvic fractures were included. Males and those aged less than 60 were excluded. Results 118 females with mean age of 79.1 ± 10.5 were included. Fourteen patients were not eligible for Teriparatide due to medical history, leaving 104 eligible patients. Twenty-eight patients (23.7%) had previous dual energy X-ray absorptiometry (DEXA) scans with mean T-scores of -3.14 ± 1.1 and 61% had Medicare insurance. Orthopaedic services recommended Teriparatide in 100% of cases. Geriatricians or endocrinologists documented evaluations for Teriparatide in 18 (17%), prescribed in 10 (9.6%), and initiated in 7 (6.7%) patients. Insurance type did not significantly differ among those that initiated Teriparatide and those that did not (p-0.10). Insurance did not approve the medication in 2 instances and in 1 instance it was discontinued at follow-up. Conclusion Despite level 1 evidence of Teriparatide's benefit for elderly osteoporotic women with low energy LC pelvic fractures, we failed to initiate treatment in 93% of eligible patients. Barriers to initiation included low rates of medical evaluation for its use and failure of insurance coverage. There are opportunities for multidisciplinary collaboration to increase evaluation for and initiation of Teriparatide. Level of Evidence Cohort Retrospective (level III evidence).
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Affiliation(s)
- David Novikov
- Division of Trauma, Department of Orthopaedics, Boston Medical Center, Boston, MA, USA
| | - Mary Grace Kelley
- Division of Trauma, Department of Orthopaedics, Boston Medical Center, Boston, MA, USA
| | - Michael S. Kain
- Division of Trauma, Department of Orthopaedics, Boston Medical Center, Boston, MA, USA
| | - Paul Tornetta
- Division of Trauma, Department of Orthopaedics, Boston Medical Center, Boston, MA, USA
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Usuki K, Ueda H, Yamaguchi T, Suzuki T, Hamaguchi T. Action observation intervention using three-dimensional movies improves the usability of hands with distal radius fractures in daily life-A nonrandomized controlled trial in women. PLoS One 2024; 19:e0294301. [PMID: 39423206 PMCID: PMC11488734 DOI: 10.1371/journal.pone.0294301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 06/10/2024] [Indexed: 10/21/2024] Open
Abstract
OBJECTIVE Prolonged immobilization of joints after distal radius fracture (DRF) causes cerebral disuse-dependent plasticity (DDP) and deterioration of upper extremity function. Action observation therapy (AOT) can improve DDP. TRIAL DESIGN This nonrandomized controlled trial (UMIN 000039973) tested the hypothesis that AOT improves hand-use difficulties during activities of daily living in patients with DRF. METHOD Right-handed women with volar locking plate fixation for DRF were divided into AOT and Non-AOT groups for a 12-week intervention. The primary outcome was difficulty in using the fractured hand, assessed with the Japanese version of the Patient-related Wrist Evaluation (PRWE). The secondary outcomes were range of motion (ROM) of the injured side and gap between measured ROM and patient-estimated ROM. The survey was administered immediately post operation and at postoperative weeks 4, 8, and 12. The AOT group used a head-mounted display and three-dimensional video during ROM exercises. The Non-AOT group used active ROM exercises alone. A generalized linear model (GLM) was used to confirm interactions and main effects by group and time period, and multiple comparisons were performed. RESULTS Thirty-five patients were assigned to the AOT group (n = 18, median age, 74 years) or the Non-AOT group (n = 17, median age, 70 years). In the GLM, PRWE Total, PRWE Specific, and PRWE Usual scores revealed interactions between groups and periods. The post-hoc test revealed that the PRWE Specific scores (z = 3.43, p = 0.02) and PRWE Usual scores (z = 7.53, p<0.01) were significantly lower in the AOT group than in the Non-AOT group at 4 weeks postoperatively, whereas PRWE Total scores (z = 3.29, p = 0.04) were lower at 8 weeks postoperatively. CONCLUSIONS These results suggested that AOT can improve hand-use difficulties in right-handed women after DRF surgery. AOT positively affects the motor imagery of patients with DRF and can reverse the patient's perceived difficulty in using the fractured hand during rehabilitation.
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Affiliation(s)
- Kengo Usuki
- Department of Rehabilitation, Graduate School of Health Sciences, Saitama Prefectural University, Saitama, Japan
- Rehabilitation Center, Kitasato University Medical Center, Saitama, Japan
| | - Hiroaki Ueda
- Rehabilitation Center, Kitasato University Medical Center, Saitama, Japan
| | | | - Takako Suzuki
- Department of Rehabilitation, Graduate School of Health Sciences, Saitama Prefectural University, Saitama, Japan
| | - Toyohiro Hamaguchi
- Department of Rehabilitation, Graduate School of Health Sciences, Saitama Prefectural University, Saitama, Japan
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Momenzadeh K, Yeritsyan D, Abbasian M, Kheir N, Hanna P, Wang J, Dosta P, Papaioannou G, Goldfarb S, Tang CC, Amar-Lewis E, Nicole Prado Larrea M, Martinez Lozano E, Yousef M, Wixted J, Wein M, Artzi N, Nazarian A. Stimulation of fracture mineralization by salt-inducible kinase inhibitors. Front Bioeng Biotechnol 2024; 12:1450611. [PMID: 39359266 PMCID: PMC11445660 DOI: 10.3389/fbioe.2024.1450611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 08/19/2024] [Indexed: 10/04/2024] Open
Abstract
Introduction Over 6.8 million fractures occur annually in the US, with 10% experiencing delayed- or non-union. Anabolic therapeutics like PTH analogs stimulate fracture repair, and small molecule salt inducible kinase (SIK) inhibitors mimic PTH action. This study tests whether the SIK inhibitor YKL-05-099 accelerates fracture callus osteogenesis. Methods 126 female mice underwent femoral shaft pinning and midshaft fracture, receiving daily injections of PBS, YKL-05-099, or PTH. Callus tissues were analyzed via RT-qPCR, histology, single-cell RNA-seq, and μCT imaging. Biomechanical testing evaluated tissue rigidity. A hydrogel-based delivery system for PTH and siRNAs targeting SIK2/SIK3 was developed and tested. Results YKL-05-099 and PTH-treated mice showed higher mineralized callus volume fraction and improved structural rigidity. RNA-seq indicated YKL-05-099 increased osteoblast subsets and reduced chondrocyte precursors. Hydrogel-released siRNAs maintained target knockdown, accelerating callus mineralization. Discussion YKL-05-099 enhances fracture repair, supporting selective SIK inhibitors' development for clinical use. Hydrogel-based siRNA delivery offers targeted localized treatment at fracture sites.
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Affiliation(s)
- Kaveh Momenzadeh
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Diana Yeritsyan
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Mohammadreza Abbasian
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Nadim Kheir
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Philip Hanna
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Jialiang Wang
- The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Pere Dosta
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United States
- Wyss Institute for Biologically-Inspired Engineering, Harvard University, Boston, MA, United States
| | - Garyfallia Papaioannou
- Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Sarah Goldfarb
- Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Cheng-Chia Tang
- Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Eliz Amar-Lewis
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United States
- Wyss Institute for Biologically-Inspired Engineering, Harvard University, Boston, MA, United States
| | - Michaela Nicole Prado Larrea
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Edith Martinez Lozano
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Mohamed Yousef
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - John Wixted
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Marc Wein
- Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Natalie Artzi
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United States
- Wyss Institute for Biologically-Inspired Engineering, Harvard University, Boston, MA, United States
| | - Ara Nazarian
- Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- Department of Mechanical Engineering, Boston University, Boston, MA, United States
- Department of Orthopaedic Surgery, Yerevan State Medical University, Yerevan, Armenia
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Ha JH, Choi YW, Moon JE, Im SB, Jeong JH. Can Over Six Months of Teriparatide Treatment Prevent the Progression of Osteoporotic Thoracolumbar Compression Fracture? Korean J Neurotrauma 2024; 20:180-190. [PMID: 39372111 PMCID: PMC11450335 DOI: 10.13004/kjnt.2024.20.e28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 08/02/2024] [Accepted: 08/05/2024] [Indexed: 10/08/2024] Open
Abstract
Objective Osteoporosis is one of the most common causes of thoracolumbar compression fractures. Teriparatide is an anabolic agent used to treat osteoporosis. This study aimed to determine whether teriparatide treatment for over 6 months could be effective in patients with osteoporotic thoracolumbar compression fractures. Methods Between July 2012 and June 2020, we reviewed 50 patients with thoracolumbar osteoporotic compression fractures who could be followed up for more than 1 year. Patients were divided into 3 groups: 11 patients who did not receive teriparatide (Group 0), 19 patients who received teriparatide for less than 5 months (Group 1), and 20 patients who received teriparatide for over 6 months (Group 2). Demographic data, visual analog scale (VAS) scores, and medical histories were reviewed. Radiographs were reviewed to evaluate the vertebral body compression ratio and kyphotic angles. Results VAS scores improved in all groups at each time point after injury. Score improvements at 6 months and 1 year between Group 0 and Groups 1 or 2 were significantly different. The compression ratio in all groups increased at each time point after injury, but the differences between Groups 0, 1, and 2 were statistically significant at 3 weeks and 6 months. While the kyphotic angle significantly increased at 1 year in all groups, the differences between the groups at each time point did not reach statistical significance. Conclusion Over 6 months of teriparatide treatment had some effects on pain in patients with osteoporotic thoracolumbar compression fractures, but did not prevent the progression of vertebral collapse.
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Affiliation(s)
- Jong-Ho Ha
- Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Youn Whan Choi
- Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Ji Eun Moon
- Department Biostatistics, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Soo-Bin Im
- Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Je Hoon Jeong
- Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
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9
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Chandran M, Akesson KE, Javaid MK, Harvey N, Blank RD, Brandi ML, Chevalley T, Cinelli P, Cooper C, Lems W, Lyritis GP, Makras P, Paccou J, Pierroz DD, Sosa M, Thomas T, Silverman S. Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review. Osteoporos Int 2024; 35:1337-1358. [PMID: 38587674 PMCID: PMC11282157 DOI: 10.1007/s00198-024-07059-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 03/06/2024] [Indexed: 04/09/2024]
Abstract
Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.
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Affiliation(s)
- M Chandran
- Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, DUKE NUS Medical School, Singapore, Singapore.
| | - K E Akesson
- Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Department of Orthopedics, Skåne University Hospital, Malmö, Sweden
| | - M K Javaid
- NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | - N Harvey
- MRC Lifecourse Epidemiology Centre, University of Southampton, NIHR Southampton Biomedical Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - R D Blank
- Garvan Institute of Medical Research, Medical College of Wisconsin, Darlinghurst, NSW, Australia
- Medical College of Wisconsin, Milwaukee, WI, USA
| | - M L Brandi
- Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Largo Palagi 1, Florence, Italy
| | - T Chevalley
- Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - P Cinelli
- Department of Trauma Surgery, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - C Cooper
- MRC Lifecourse Epidemiology Centre, University of Southampton, NIHR Southampton Biomedical Research Centre, University of Southampton, University Hospitals Southampton NHS Foundation Trust, Southampton, UK
- NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, UK
| | - W Lems
- Department of Rheumatology, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands
| | - G P Lyritis
- Hellenic Osteoporosis Foundation, Athens, Greece
| | - P Makras
- Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece
| | - J Paccou
- Department of Rheumatology, MABlab ULR 4490, CHU Lille, Univ. Lille, 59000, Lille, France
| | - D D Pierroz
- International Osteoporosis Foundation, Nyon, Switzerland
| | - M Sosa
- University of Las Palmas de Gran Canaria, Investigation Group on Osteoporosis and Mineral Metabolism, Canary Islands, Spain
| | - T Thomas
- Department of Rheumatology, North Hospital, CHU Saint-Etienne and INSERM U1059, University of Lyon-University Jean Monnet, Saint‑Etienne, France
| | - S Silverman
- Cedars-Sinai Medical Center and Geffen School of Medicine UCLA, Los Angeles, CA, USA
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10
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Song G, Jeong Y, Nam WD, Kim KH. Teriparatide Does not Have Beneficial Effects on Bone Healing in Complete Atypical Femur Fractures. Calcif Tissue Int 2024; 115:169-173. [PMID: 38907093 DOI: 10.1007/s00223-024-01244-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 06/01/2024] [Indexed: 06/23/2024]
Abstract
Teriparatide is an anabolic drug sometimes administered to patients who have atypical femoral fracture (AFF). However, whether teriparatide has beneficial effects on bone healing remains uncertain. The present study aimed to analyze the association between teriparatide and bone healing in complete AFF. A total of 59 consecutive cases (58 patients) who underwent intramedullary nailing for complete AFF were categorized based on postoperative use of teriparatide into the non-teriparatide (non-TPTD, n = 34) and teriparatide groups (TPTD, n = 25). Time-to-bone union was evaluated and compared between the two groups. Additionally, multiple regression analysis was performed to evaluate factors affecting time-to-bone union. All participants were women, with a mean age of 77.6 years (range: 62-92). No significant difference in time-to-bone union was found between the non-TPTD and TPTD groups (5.5 months vs. 5.8 months, p = 0.359). Two patients in the non-TPTD group underwent reoperation (p = 0.503) due to failure caused by inadequate fixation, and both achieved bone healing after additional fixation with blocking screws. Multiple regression analysis revealed that the anterior gap of the fracture site postoperatively was a factor affecting time-to-bone union (p = 0.014). The beneficial effect of teriparatide on bone healing in complete AFF could not be confirmed. Additional randomized controlled trials are required. Nonetheless, appropriate techniques, including efforts to reduce the gap on the tensile side during the surgery, are important for reliable bone healing.
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Affiliation(s)
- Gill Song
- Department of Orthopaedic Surgery, College of Medicine Kangwon National University, Kangwon National University Hospital, Baengnyeong-Ro 156, Chuncheon-si, Gangwon-do, 24289, Republic of Korea
| | - Yerang Jeong
- Department of Orthopaedic Surgery, College of Medicine Kangwon National University, Kangwon National University Hospital, Baengnyeong-Ro 156, Chuncheon-si, Gangwon-do, 24289, Republic of Korea
| | - Woo Dong Nam
- Department of Orthopaedic Surgery, College of Medicine Kangwon National University, Kangwon National University Hospital, Baengnyeong-Ro 156, Chuncheon-si, Gangwon-do, 24289, Republic of Korea
| | - Keong-Hwan Kim
- Department of Orthopaedic Surgery, College of Medicine Kangwon National University, Kangwon National University Hospital, Baengnyeong-Ro 156, Chuncheon-si, Gangwon-do, 24289, Republic of Korea.
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11
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Ganse B. Methods to accelerate fracture healing - a narrative review from a clinical perspective. Front Immunol 2024; 15:1384783. [PMID: 38911851 PMCID: PMC11190092 DOI: 10.3389/fimmu.2024.1384783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 05/14/2024] [Indexed: 06/25/2024] Open
Abstract
Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors. Fracture healing usually takes several weeks to months, during which patients are frequently immobilized and unable to work. As immobilization is associated with negative health and socioeconomic effects, it would be desirable if fracture healing could be accelerated and the healing time shortened. However, interventions for this purpose are not yet part of current clinical treatment guidelines, and there has never been a comprehensive review specifically on this topic. Therefore, this narrative review provides an overview of the available clinical evidence on methods that accelerate fracture healing, with a focus on clinical applicability in healthy patients without bone disease. The most promising methods identified are the application of axial micromovement, electromagnetic stimulation with electromagnetic fields and direct electric currents, as well as the administration of growth factors and parathyroid hormone. Some interventions have been shown to reduce the healing time by up to 20 to 30%, potentially equivalent to several weeks. As a combination of methods could decrease the healing time even further than one method alone, especially if their mechanisms of action differ, clinical studies in human patients are needed to assess the individual and combined effects on healing progress. Studies are also necessary to determine the ideal settings for the interventions, i.e., optimal frequencies, intensities, and exposure times throughout the separate healing phases. More clinical research is also desirable to create an evidence base for clinical guidelines. To make it easier to conduct these investigations, the development of new methods that allow better quantification of fracture-healing progress and speed in human patients is needed.
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Affiliation(s)
- Bergita Ganse
- Innovative Implant Development (Fracture Healing), Clinics and Institutes of Surgery, Saarland University, Homburg, Germany
- Department of Trauma, Hand and Reconstructive Surgery, Clinics and Institutes of Surgery, Saarland University, Homburg, Germany
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12
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Jeon I, Park SB, Moon BJ, Choi M, Kuh SU, Kim J. Comparison of the Clinical Efficacy of Anabolic Agents and Bisphosphonates in the Patients With Osteoporotic Vertebral Fracture: Systematic Review and Meta-analysis of Randomized Controlled Trials. Neurospine 2024; 21:416-429. [PMID: 38697911 PMCID: PMC11224729 DOI: 10.14245/ns.2347256.628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 01/03/2024] [Accepted: 02/04/2024] [Indexed: 05/05/2024] Open
Abstract
OBJECTIVE We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs). METHODS Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) ver. 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively. RESULTS Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs. alendronate and risedronate [RR, 0.57; 95% confidence interval, 0.45-0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs. risedronate [RR, 0.50; 95% confidence interval, 0.37-0.68; p < 0.0001; high-certainty of evidence]). However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR, 1.23; 95% confidence interval, 0.95-1.60; p = 0.12; low-certainty of evidence). CONCLUSION In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.
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Affiliation(s)
- Ikchan Jeon
- Department of Neurosurgery, Yeungnam University Hospital, Yeungnam University College of Medicine, Daegu, Korea
| | - Sung Bae Park
- Department of Neurosurgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Bong Ju Moon
- Department of Neurosurgery, Spine and Spinal Cord Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Miyoung Choi
- Clinical Evidence Research, Division of Health Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea
| | - Sung Uk Kuh
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jongtae Kim
- Department of Neurosurgery, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
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13
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Makino A, Hasegawa T, Yamamoto T, Takagi H, Takahashi Y, Miyakoshi N, Amizuka N. Abaloparatide promotes bone repair of vertebral defects in ovariectomized rats by increasing bone formation. Bone 2024; 182:117056. [PMID: 38402920 DOI: 10.1016/j.bone.2024.117056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 02/07/2024] [Accepted: 02/19/2024] [Indexed: 02/27/2024]
Abstract
Osteoporotic vertebral fracture (OVF) is the most common type of osteoporotic fracture and is associated with immobility and mortality. Bone anabolic agents, such as abaloparatide (ABL), are usually administered to patients with OVF to prevent subsequent fractures. Although several studies have shown that bone anabolic agents promote healing of long bone fractures, there is little evidence of their healing effect on vertebral bone fractures. In the present study, we investigated the effect of ABL on vertebral bone defects using ovariectomized (OVX) rats with vertebral body drill-hole defects, an animal model of OVF. Eight-week-old female Sprague-Dawley rats were subjected to OVX, followed by the 32-36 days of bone depletion period, once-daily subcutaneous ABL was administered to OVX rats at a dose of 30 μg/kg for a maximum of 6 weeks from the day of the vertebral defect surgery. We found that ABL significantly increased bone mineral content and improved trabecular structural parameters at the vertebral defect site. Moreover, ABL significantly increased bone strength of the defected vertebrae. Bone histochemical analysis revealed formation of thick trabecular bone networks at the defect site after ABL administration, consistent with an improvement in trabecular structural parameters by ABL. ABL increased ALPase- and PHOSPHO1-positive osteoblastic cells and ALPase/PCNA double-positive cells, indicating enhanced preosteoblast proliferation as well as bone formation at the defect site. On the other hand, ABL did not affect the number of cathepsin K-positive osteoclasts per bone surface, suggesting that ABL did not promote excessive bone resorption. Our findings suggest that ABL is useful not only for preventing secondary vertebral fractures but also for promoting bone healing in OVF.
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Affiliation(s)
- Akito Makino
- Pharmacology Research Department, Teijin Pharma Limited, Tokyo, Japan.
| | - Tomoka Hasegawa
- Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan
| | - Tomomaya Yamamoto
- Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan
| | - Hideko Takagi
- Pharmacology Research Department, Teijin Pharma Limited, Tokyo, Japan
| | | | - Naohisa Miyakoshi
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Norio Amizuka
- Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan
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14
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Salamah HM, Abualkhair KA, Kamal SK, Mohamed HA, Alkheder A, Farho MA, Mistry D, Elbardesy H. The effect of teriparatide on patients with atypical femur fractures: a systematic review and meta-analysis. Arch Orthop Trauma Surg 2024; 144:1091-1106. [PMID: 38135789 PMCID: PMC10896930 DOI: 10.1007/s00402-023-05171-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 11/27/2023] [Indexed: 12/24/2023]
Abstract
INTRODUCTION Bisphosphonates (BPs) are one of the most often used drugs to lower fracture risk in osteoporosis patients; nonetheless, BPs have been linked to atypical femoral fracture (AFF). Teriparatide (TPTD) is a parathyroid hormone analogue and anabolic drug that may accelerate fracture repair. TPTD has been considered as a possible treatment for AFF, particularly those caused by BP use. We evaluate the effect of TPTD on AFF in this systematic review and meta-analysis. MATERIALS AND METHODS A thorough search of: Web of Science, Scopus, PubMed, and Cochrane was conducted on August 2, 2023. Trials evaluating the effect of TPTD on the incidence of: complete bone healing, non-union, early and delayed bone union, progression of incomplete AFF to complete AFF, and time to bone union were included. Using Review Manager (RevMan) version 5.4, the risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence interval (CI) were estimated for dichotomous and continuous outcomes, respectively. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS Eight studies met the eligibility criteria and were included in our analysis. TPTD significantly increased the incidence of early bone union (RR = 1.45, 95% CI [1.13, 1.87], P = 0.004) and time to bone union (MD = -1.56, 95% CI [-2.86, -0.26], P = 0.02) compared to the control group. No significant differences were observed in terms of complete bone healing (RR = 1.09, 95% CI [0.99, 1.13], P = 0.12), non-union (RR = 0.48, 95% CI [0.22, 1.04], P = 0.06), and progression of incomplete AFF to complete AFF (RR = 0.27, 95% CI [0.04, 1.97], P = 0.19). CONCLUSIONS TPTD is an effective therapy for enhancing and hastening healing following AFF, particularly in postoperative settings. Future large randomized clinical trials are needed to confirm or dispute the results.
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Affiliation(s)
| | | | - Sara K Kamal
- Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hazem A Mohamed
- Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt
| | - Ahmad Alkheder
- Department of Otorhinolaryngology, Al Mouwasat University Hospital, Faculty of Medicine, Damascus University, Damascus, Syria
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | | | - Dillan Mistry
- Department of Orthopaedics Mid Yorkshire Hospitals, Leeds, UK
| | - Hany Elbardesy
- Department of Trauma and Orthopaedics, Liverpool University Hospitals, Liverpool, UK
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15
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Ting M, Huynh BH, Woldu HG, Gamal I, Suzuki JB. Clinical Impact on Dental Implant Survival in Patients Taking Antiresorptive Medications: A Systematic Review and Meta-Analysis. J ORAL IMPLANTOL 2023; 49:599-615. [PMID: 37905745 DOI: 10.1563/aaid-joi-d-21-00160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2023]
Abstract
Dental implants are a predictable option to replace missing teeth. Patients on antiresorptive medications used to treat disorders associated with bone resorption may need dental implants to replace missing teeth. The data on implant failure in patients on antiresorptive medication requiring dental implants, is conflicting and limited. This systematic review aims to investigate if antiresorptive medications have any clinical impact on dental implant survival. Electronic databases were searched until May 2020. The focus question (PICOS): Participants: humans, Interventions: implant placement surgery in patients on antiresorptive medication, Comparisons: patients on antiresorptive medication vs control (patients not on antiresorptive medication), Outcomes: implant survival, and Study design: clinical studies. The protocol of this systematic review was registered in PROSPERO (CRD42020209083). Fourteen nonrandomized studies were selected for data extraction and risk of bias assessment using the ROBINS-1 tool. Only studies with a control were included for the meta-analysis, 8 articles were included in the meta-analysis using implant-level data, and 5 articles were included in the meta-analysis using patient-level data. There was no statistical significance between the 2 groups at the patient level based on 265 patients. However, there was a statistically significant difference at the implant level based on 2697 implants. Therefore, antiresorptive medications, mainly bisphosphonates (BPs), may significantly contribute to implant failure. Antiresorptive medications, especially BPs may reduce implant survival and impair the osseointegration of dental implants. Failed implants in patients on BPs may not lead to osteonecrosis and may be replaced with success.
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Affiliation(s)
- Miriam Ting
- Department of Periodontics, University of Pennsylvania, Philadelphia, PA
- Think Dental Learning Institute, Paoli, PA
- General Dental Practice Residency, Einstein Medical Center, Philadelphia, PA
- Private Practice, Paoli, PA
| | - Benzon H Huynh
- Indian Health Service, U.S. Department of Health and Human Services
| | - Henok G Woldu
- The Center for Health Analytics for National and Global Equity (C.H.A.N.G.E.), Columbia, MO
- Biostatistician, Private Company, CA
| | - Ibrahim Gamal
- Faculty of Medicine, Al Azhar University, Cairo, Egypt
| | - Jon B Suzuki
- University of Maryland School of Dentistry, Baltimore, MD
- University of Washington School of Dentistry, Seattle, WA
- Nova Southeastern University College of Dental Medicine, Fort Lauderdale, FL
- Temple University Schools of Medicine and Dentistry, Philadelphia, PA
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16
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Nozaka K, Miyakoshi N, Mita M, Shimada Y. The successful treatment of a Gustilo-Anderson type IIIc distal leg injury with a large bone defect in elderly patient with severe osteoporosis: a case report. J Med Case Rep 2023; 17:452. [PMID: 37828610 PMCID: PMC10571402 DOI: 10.1186/s13256-023-04193-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 01/06/2023] [Indexed: 10/14/2023] Open
Abstract
BACKGROUND Gustilo-Anderson type IIIc tibial open fracture with large bone defects in elderly patients with severe osteoporosis is a rare injury that may be a challenging clinical scenario. CASE PRESENTATION This study presents the case of a 68-year-old Japanese man who sustained a Gustilo-Anderson type IIIc open tibial fracture with a large bone defect. The patient had severe osteoporosis and the bone was contaminated; therefore, we determined that the bone could not be returned to the tibia. The patient underwent acute limb shortening and gradual lengthening with an Ilizarov external fixator combined with low-intensity pulsed ultrasound and teriparatide administration for limb reconstruction, which allowed immediate full weight-bearing capacity. The fixator was removed at 12 months postoperatively, and by this time, the fracture had completely healed. At the most recent 5-year follow-up after the injury, the patient reported full weight-bearing capacity without walking aids and had full knee and ankle range of motion. CONCLUSIONS To the best of our knowledge, this is the first study to report the use of combined Ilizarov technique, low-intensity pulsed ultrasound, and teriparatide for limb reconstruction of Gustilo-Anderson type IIIc open tibial fractures with large bone defects in elderly patients with severe osteoporosis.
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Affiliation(s)
- Koji Nozaka
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
| | - Naohisa Miyakoshi
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Motoki Mita
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Yoichi Shimada
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
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17
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Kitcharanant N, Chattipakorn N, Chattipakorn SC. The effect of intermittent parathyroid hormone on bone lengthening: current evidence to inform future effective interventions. Osteoporos Int 2023; 34:1657-1675. [PMID: 37286663 DOI: 10.1007/s00198-023-06809-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 05/25/2023] [Indexed: 06/09/2023]
Abstract
PURPOSE Recent studies have demonstrated the positive effects of parathyroid hormone (PTH) on bone healing, and findings support the use of PTH to accelerate bone healing following distraction osteogenesis. The goal of this review was to compile and discuss the mechanisms potentially underlying the effects of PTH on newly formed bone following a bone-lengthening procedure incorporating all relevant evidence in both animal and clinical studies. METHODS This review summarized all evidence from in vivo to clinical studies regarding the effects of PTH administration on a bone-lengthening model. In addition, a comprehensive evaluation of what is currently known regarding the potential mechanisms underlying the potential benefits of PTH in bone lengthening was presented. Some controversial findings regarding the optimal dosage and timing of administration of PTH in this model were also discussed. RESULTS The findings demonstrated that the potential mechanisms associated with the action of PTH on the acceleration of bone regeneration after distraction osteogenesis are involvement in mesenchymal cell proliferation and differentiation, endochondral bone formation, membranous bone formation, and callus remodeling. CONCLUSIONS In the last 20 years, a number of animal and clinical studies have indicated that there is a prospective role for PTH treatment in human bone lengthening as an anabolic agent that accelerates the mineralization and strength of the regenerated bone. Therefore, PTH treatment can be viewed as a potential treatment to increase the amount of new calcified bone and the mechanical strength of the bone in order to shorten the consolidation stage after bone lengthening.
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Affiliation(s)
- Nitchanant Kitcharanant
- Department of Orthopaedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Siriporn C Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand.
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18
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Kwon HK, Cahill SV, Yu KE, Alder KD, Dussik CM, Jeong J, Back JH, Lee FY. Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model. Front Cell Infect Microbiol 2023; 13:1230568. [PMID: 37829606 PMCID: PMC10565816 DOI: 10.3389/fcimb.2023.1230568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 08/28/2023] [Indexed: 10/14/2023] Open
Abstract
Introduction Diabetes mellitus (DM) impairs fracture healing and is associated with susceptibility to infection, which further inhibits fracture healing. While intermittent parathyroid hormone (1-34) (iPTH) effectively improves fracture healing, it is unknown whether infection-associated impaired fracture healing can be rescued with PTH (teriparatide). Methods A chronic diet-induced type 2 diabetic mouse model was used to yield mice with decreased glucose tolerance and increased blood glucose levels compared to lean-fed controls. Methicillin-resistant Staphylococcus aureus (MRSA) was inoculated in a surgical tibia fracture model to simulate infected fracture, after which mice were treated with a combination of antibiotics and adjunctive teriparatide treatment. Fracture healing was assessed by Radiographic Union Scale in Tibial Fractures (RUST), micro-computed tomography (μCT), biomechanical testing, and histology. Results RUST score was significantly poorer in diabetic mice compared to their lean nondiabetic counterparts. There were concomitant reductions in micro-computed tomography (μCT) parameters of callus architecture including bone volume/total volume, trabecular thickness, and total mineral density in type 2 diabetes mellitus (T2DM) mice. Biomechanicaltesting of fractured femora demonstrated diminished torsional rigidity, stiffness, and toughness to max torque. Adjuvant teriparatide treatment with systemic antibiotic therapy improved numerous parameters of bone microarchitecture bone volume, increased connectivity density, and increased trabecular number in both the lean and T2DM group. Despite the observation that poor fracture healing in T2DM mice was further impaired by MRSA infection, adjuvant iPTH treatment significantly improved fracture healing compared to antibiotic treatment alone in infected T2DM fractures. Discussion Our results suggest that teriparatide may constitute a viable adjuvant therapeutic agent to improve bony union and bone microarchitecture to prevent the development of septic nonunion under diabetic conditions.
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Affiliation(s)
- Hyuk-Kwon Kwon
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, United States
- Division of Life Science, Gyeongsang National University, Jinju, Republic of Korea
| | - Sean V. Cahill
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, United States
| | - Kristin E. Yu
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, United States
| | - Kareme D. Alder
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, United States
| | - Christopher M. Dussik
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, United States
| | - Jain Jeong
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, United States
| | - Jung Ho Back
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, United States
| | - Francis Y. Lee
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, United States
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19
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Gera I, Szücs N. [The recombinant human parathyroid hormone, teriparatide as an alternative remedy for the medication-related osteonecrosis of the jaw]. Orv Hetil 2023; 164:1406-1415. [PMID: 37695713 DOI: 10.1556/650.2023.32861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 06/30/2023] [Indexed: 09/13/2023]
Abstract
In developed countries, osteoporosis is one of the most common debilitating conditions in the population over the age of 50. Unfortunately, the pathomechanism of the disease is still not fully understood. Nowadays, the administration of antiresorptive drugs blocking osteoclastic activity is the most commonly used medication to slow down the speed of the bone loss. One of the uncommon side effects of such drugs is the medication-related osteonecrosis of the jaw (MRONJ). Recently, a number of alternative therapeutic approaches has been tested and published, amongst them the recombinant human parathyroid hormone (rhPTH, teriparatide) use, which is turning into a promising treatment modality. According to certain meta-analyses, its pharmacological effect on increasing bone mineral density and controlling pathological vertebral fractures is superior to antiresorptive drugs; however, the so-called "off-label" application of teriparatide remains controversial. As intermittent administration of teriparatide stimulates bone formation, several animal and clinical studies indicated that systemic application of teriparatide shortened fracture healing time and improved quality of the callus and the newly formed bone. Furthermore, recently several clinical studies showed the beneficial effect of the intermittent rhPTH administration in the management of MRONJ. This article reviews the history of the anabolic effect of the low-dose rhPTH discovery, provides evidence-based data from animal and human studies, summarizes its biological mechanisms and the clinical benefits of the anabolic therapy and also their possible role in the management of MRONJ. The majority of the clinical data indicates that, in the case of therapy-resistant osteonecrosis, it may be worthwhile to apply short-term intermittent teriparatide therapy. Notwithstanding, more randomized clinical trials are necessary in order to confirm the efficacy and the safety of the use of teriparatide in the treatment of MRONJ. Orv Hetil. 2023; 164(36): 1406-1415.
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Affiliation(s)
- István Gera
- 1 Semmelweis Egyetem, Fogorvostudományi Kar, Parodontológiai Klinika Budapest, Szentkirályi u. 47., 1088 Magyarország
| | - Nikolette Szücs
- 2 Semmelweis Egyetem, Általános Orvostudományi Kar, Belgyógyászati és Onkológiai Klinika Budapest Magyarország
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20
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Ruan Z, Yin H, Wan TF, Lin ZR, Zhao SS, Long HT, Long C, Li ZH, Liu YQ, Luo H, Cheng L, Chen C, Zeng M, Lin ZY, Zhao RB, Chen CY, Wang ZX, Liu ZZ, Cao J, Wang YY, Jin L, Liu YW, Zhu GQ, Zou JT, Gong JS, Luo Y, Hu Y, Zhu Y, Xie H. Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression. Bone Res 2023; 11:45. [PMID: 37587136 PMCID: PMC10432554 DOI: 10.1038/s41413-023-00279-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 06/04/2023] [Accepted: 06/26/2023] [Indexed: 08/18/2023] Open
Abstract
Due to increasing morbidity worldwide, fractures are becoming an emerging public health concern. This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures. Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis. Here, we show that metformin accelerated fracture healing in both osteoporotic and normal mice. Moreover, metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing. Mechanistically, metformin increased the expression of HIF-1α, an important positive regulator of type H vessel formation, by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells (HMECs). The results of HIF-1α or YAP1/TAZ interference in hypoxia-cultured HMECs using siRNA further suggested that the enhancement of HIF-1α and its target genes by metformin is primarily through YAP1/TAZ inhibition. Finally, overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair. In summary, our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.
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Affiliation(s)
- Zhe Ruan
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Hao Yin
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Teng-Fei Wan
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Zhi-Rou Lin
- The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Shu-Shan Zhao
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Hai-Tao Long
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Cheng Long
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Zhao-Hui Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yu-Qi Liu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Hao Luo
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Liang Cheng
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Can Chen
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Min Zeng
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Zhang-Yuan Lin
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Rui-Bo Zhao
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Chun-Yuan Chen
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Zhen-Xing Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Zheng-Zhao Liu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Jia Cao
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yi-Yi Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Ling Jin
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Yi-Wei Liu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Guo-Qiang Zhu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Jing-Tao Zou
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Jiang-Shan Gong
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Yi Luo
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China
| | - Yin Hu
- The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Yong Zhu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
| | - Hui Xie
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
- Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China.
- Angmedicine Research Center of Central South University, Changsha, Hunan, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
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21
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Lee SY, Seo MS, Yoo JI. Effectiveness of Weekly Teriparatide Injection in Postmenopausal Patients with Hip Fractures. Clin Orthop Surg 2023; 15:552-559. [PMID: 37529188 PMCID: PMC10375812 DOI: 10.4055/cios22280] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 11/17/2022] [Accepted: 11/17/2022] [Indexed: 08/03/2023] Open
Abstract
Background Teriparatide is an effective anabolic agent used in the treatment of severe osteoporosis. In addition, it is also used to promote fracture healing. The purpose of this double-blind randomized controlled trial was to evaluate the influence of weekly teriparatide administration on bone formation in hip fracture patients. Methods The control group (n = 41) was composed of patients treated with normal saline other than teriparatide, and the teriparatide group (n = 51) consisted of patients who received weekly teriparatide. Bone turnover markers, C-terminal telopeptide (CTx) and osteocalcin (OC), were assessed through blood tests at the initial hospital visit and 3-month, 6-month, and 1-year follow-ups. Dual-energy X-ray absorptiometry was performed 5 days postoperatively and at 1-year postoperative follow-up. The degree of fracture union was evaluated by comparing the radiographic union scoring system for hips using Radiographic Union Score for Hip (RUSH) scores between the two groups at 3 months, 6 months, and 1 year after surgery. Results Evaluation of the rate of change in bone mineral density over 1 year showed that the lumber bone mineral density increased by more than 7% in the experimental group. The control group did not show a difference between the CTx and OC at 6 months, but the difference between the CTx and OC values was large at 6 months in the experimental group. The mean RUSH score was significantly different between the control group and the experimental group: 12.105 and 15.476, respectively (p = 0.004), at 3 months and 18.571 and 22.389, respectively, at 6 months (p = 0.006). Conclusions Weekly use of teriparatide improved fracture healing, bone formation, and clinical outcomes at 1 year after hip fracture surgery by the anabolic window effect.
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Affiliation(s)
- Sang Yeob Lee
- Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Korea
| | - Min-Seok Seo
- Department of Orthopaedic Surgery, Gyeongsang National University Hospital, Jinju, Korea
| | - Jun-Il Yoo
- Department of Orthopaedic Surgery, Gyeongsang National University Hospital, Jinju, Korea
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22
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Migliorini F, Cocconi F, Vecchio G, Schäefer L, Koettnitz J, Maffulli N. Pharmacological agents for bone fracture healing: talking points from recent clinical trials. Expert Opin Investig Drugs 2023; 32:855-865. [PMID: 37740660 DOI: 10.1080/13543784.2023.2263352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 09/22/2023] [Indexed: 09/24/2023]
Abstract
INTRODUCTION Pharmacological strategies might influence bone healing in terms of time to union or quality of mature bone. This expert opinion discussed the current level I evidence on the experimental pharmacological agents used to favor bone fracture healing. AREAS COVERED This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the 2020 PRISMA statement. In April 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, Embase. All the randomized clinical trials investigating pharmacological agents for bone fracture healing were accessed. No time constraint was set for the search. The search was restricted to RCTs. No additional filters were used in the database search. Data from 19 RCTs (4067 patients) were collected. 78% (3160 of 4067) were women. The mean length of the follow-up was 9.3 months (range, 1-26 months). The mean age of the patients was 64.4 years (range, 8-84 years). EXPERT OPINION Calcitonin could favor bone fracture healing. Bisphosphonates (alendronate, zoledronate, clodronate), monoclonal antibodies (denosumab, romosozumab), statins, vitamin D and calcium supplementation, strontium ranelate, and ibuprofen did not influence bony healing. Concerning the effect of parathormone, current level I evidence is controversial, and additional studies are required. LEVEL OF EVIDENCE Level I, systematic review of RCTs.
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Affiliation(s)
- Filippo Migliorini
- Department of Orthopaedic, Trauma, and Reconstructive Surgery, RWTH University Medical Centre, Aachen, Germany
| | - Federico Cocconi
- Department of Orthopedics and Trauma Surgery, Academic Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsus Medical University, Bolzano, Italy
| | - Gianluca Vecchio
- Department of Trauma and Orthopaedic Surgery, University Hospital Sant' Andrea, University La Sapienza, Rome, Italy
| | - Luise Schäefer
- Department of Orthopaedic, Trauma, and Reconstructive Surgery, RWTH University Medical Centre, Aachen, Germany
| | - Julian Koettnitz
- Department of Orthopedics, Auguste-Viktoria Clinic, Ruhr University Bochum, Bad Oeynhausen, Germany
| | - Nicola Maffulli
- Department of Trauma and Orthopaedic Surgery, University Hospital Sant' Andrea, University La Sapienza, Rome, Italy
- School of Pharmacy and Bioengineering, Keele University Faculty of Medicine, Stoke on Trent, UK
- Centre for Sports and Exercise Medicine, Barts and the London School of Medicine and Dentistry, Mile End Hospital, Queen Mary University of London, London, UK
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23
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El Miedany Y, Toth M, Elwakil W, Saber S. Post-Fracture Care Program: Pharmacological Treatment of Osteoporosis in Older Adults with Fragility Fractures. Curr Osteoporos Rep 2023:10.1007/s11914-023-00791-w. [PMID: 37300602 DOI: 10.1007/s11914-023-00791-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/22/2023] [Indexed: 06/12/2023]
Abstract
PURPOSE OF REVIEW To present and discuss the recently published scientific evidence on the approach, mode of action, and timing of osteoporosis therapy initiation after fragility fractures. RECENT FINDINGS A comprehensive management approach is required to reduce mortality and morbidity associated with fragility fractures. This will help to reduce the risk of missing the diagnosis of osteoporosis as the underlying disorder while at the same time promoting the timely treatment of osteoporosis. The target is to minimize the incidence of post-traumatic disability and to reduce the imminent fracture risk. This article will present a Bone-Care algorithm for the diagnosis and management of fragility fractures in patients presenting for trauma surgery. This algorithm has been developed based on recently published national as well as international guidelines for implementation in standard clinical practice. International figures revealed that only a small proportion of those patients at high risk of sustaining a fragility fracture receive osteoporosis therapy. Based on the best currently available evidence, it is safe to start osteoporosis therapy in the acute post-fracture period (the optimal therapeutic window of romosozumab is the late endochondral phase/throughout bone remodeling). The right Bone-Care pathway ensures the delivery of a comprehensive management approach that meets the global call to action. All parameters including risk, benefit, compliance, and cost should be considered on an individual base for all kinds of therapy.
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Affiliation(s)
- Yasser El Miedany
- Institute of Medical Sciences, Canterbury Christ Church University, Canterbury, UK.
| | - Mathias Toth
- King's College, London, UK
- Darent Valley Hospital, Kent, UK
| | - Walaa Elwakil
- Rheumatology, Physical Medicine and Rehabilitation, Alexandria University, Alexandria, Egypt
| | - Sally Saber
- Rheumatology and Rehabilitation, Ain Shams University, Cairo, Egypt
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24
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Fukui T, Oe K, Kawamoto T, Morishita M, Fujita I, Takahara S, Sakurai A, Iwakura T, Yoshida K, Ito K, Shoda E, Hiranaka T, Tsunoda M, Kuroda R, Niikura T. Multicenter study on atypical femoral fractures in patients with bone metastases taking bone- modifying agents. J Bone Oncol 2023; 40:100478. [PMID: 37180736 PMCID: PMC10173009 DOI: 10.1016/j.jbo.2023.100478] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/02/2023] [Accepted: 04/08/2023] [Indexed: 05/16/2023] Open
Abstract
Bone-modifying agents (BMAs), with bone-resorptive inhibitory effects, such as zoledronic acid and denosumab, are widely used at higher doses for bone-related events caused by bone metastasis of malignant tumors. These drugs have been suggested to be associated with atypical femoral fractures (AFFs), and the relationship between BMAs and AFFs has attracted attention. To investigate the clinical features including bone union time of AFFs in patients administered BMA for bone metastasis, we conducted a retrospective multicenter study. Thirty AFFs from 19 patients were enrolled in this study. Thirteen patients had bilateral AFFs, and nineteen AFFs had prodromal symptoms. Eighteen AFFs underwent surgery after complete fracture, three failed to achieve bone union and required nonunion surgery, and 11 AFFs that achieved bone union had an average period until bone union of 16.2 months, which was much longer than that previously reported for ordinary AFFs. Seven patients discontinued the BMAs, but not due to AFFs. Stopping BMAs in patients with bone metastasis would make it difficult to secure their performance of activities of daily living, and AFF with BMA administration might require a longer time for union. Therefore, it would be important to prevent incomplete AFF from becoming complete AFF via prophylactic internal fixation.
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Affiliation(s)
- Tomoaki Fukui
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Japan
| | - Keisuke Oe
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Japan
| | - Teruya Kawamoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Japan
| | | | - Ikuo Fujita
- Department of Orthopaedic Surgery, Hyogo Cancer Center, Japan
| | | | - Atsushi Sakurai
- Department of Orthopaedic Surgery, Awaji Medical Center, Japan
| | - Takashi Iwakura
- Department of Orthopaedic Surgery, Awaji Medical Center, Japan
- Department of Orthopaedic Surgery, Sanda City Hospital, Japan
| | - Keiji Yoshida
- Department of Orthopaedic Surgery, Kobe City Nishi-Kobe Medical Center, Japan
| | - Kenjiro Ito
- Department of Orthopaedic Surgery, Akashi Medical Center, Japan
| | - Etsuo Shoda
- Department of Orthopaedic Surgery, Hyogo Prefectural Nishinomiya Hospital, Japan
| | | | - Masaya Tsunoda
- Department of Orthopaedic Surgery, Sanda City Hospital, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Japan
| | - Takahiro Niikura
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Japan
- Department of Orthopaedic Surgery, Hyogo Prefectural Nishinomiya Hospital, Japan
- Corresponding author at: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Japan.
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25
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Puvvada CS, Marripaty JS. Using Teriparatide to Augment Healing in a Humeral Shaft Nonunion: A Case Report. Cureus 2023; 15:e39546. [PMID: 37378240 PMCID: PMC10291988 DOI: 10.7759/cureus.39546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2023] [Indexed: 06/29/2023] Open
Abstract
The occurrence of complications of fracture healing, such as delayed union and nonunion, is well known, but the use of pharmacotherapy for these delayed unions and nonunions has not been explored in detail. The authors describe a case of traumatic humeral shaft fracture successfully treated with once-daily administration of 20mcg of teriparatide for six months. The patient was a 22-year-old male who had been through a road traffic accident. The radiograph of the humerus shaft showed a fracture line and the displaced distal portion of the shaft of the humerus. Based on these features, the patient was diagnosed with a humeral shaft fracture. The patient underwent internal fixation with a dynamic compression plate. However, there were no signs of callus formation even after 12 weeks from the time of internal fixation. The patient was initiated with teriparatide administration and union was achieved after six months of a once-daily administration of teriparatide. Once-daily teriparatide treatment is shown to be beneficial for improving the healing of humeral shaft fractures showing delayed union.
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Affiliation(s)
- Chaitanya S Puvvada
- General Surgery, Gayatri Vidya Parishad Institute of Health Care and Medical Technology, Visakhapatnam, IND
| | - Jaithra S Marripaty
- General Surgery, Gayatri Vidya Parishad Institute of Health Care and Medical Technology, Visakhapatnam, IND
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Puvvada CS, Soomro FH, Osman HA, Haridi M, Gonzalez NA, Dayo SM, Fatima U, Sheikh A, Penumetcha SS. Efficacy and Safety of Teriparatide in Improving Fracture Healing and Callus Formation: A Systematic Review. Cureus 2023; 15:e37478. [PMID: 37187628 PMCID: PMC10177009 DOI: 10.7759/cureus.37478] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
Fracture nonunion remains a great challenge for orthopedic surgeons. Some bone fractures don't heal promptly, resulting in delayed unions and nonunions, and there is a need for an additional surgical procedure. Previous research has shown that teriparatide, a type of synthetic parathyroid hormone, can promote the formation of callus and lead to healing in individuals with delayed or non-healing bone fractures. Limited systematic reviews exist that examine the use of teriparatide in cases of delayed healing or non-healing bone fractures, which have their limitations. In this review, we overcome those limitations by including prospective studies, retrospective studies, case reports, and case series together. A systematic search of the literature was conducted in both PubMed and Google Scholar up to September of the year 2022. The studies included in our research included adult patients (over the age of 16) diagnosed with delayed union or nonunion of any bone in the body (flat bone, long bone, short bone, or irregular bone). The studies were limited to those written in English. The outcomes that were tracked and recorded include the healing of the fracture and any negative side effects or adverse events. The initial search yielded 504 abstracts and titles. After reviewing these, 32 articles were selected for further analysis, which included 19 case reports, five case series, two retrospective studies, and six prospective studies. Studies included daily (20 micrograms) or weekly (56.5 micrograms) subcutaneous administration of teriparatide. The duration of follow-up for these studies varied from three to 24 months. Based on the available research, it appears that administering teriparatide subcutaneously is a safe treatment option for delayed healing and non-healing bone fractures, with very few to no reported negative side effects. Using teriparatide for induction of callus formation and treating delayed and nonunions is highly safe and effective.
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Affiliation(s)
- Chaitanya S Puvvada
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Gayatri Vidya Parishad Institute of Health Care and Medical Technology, Visakhapatnam, IND
| | - Faiza H Soomro
- General Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- General Surgery, NineWells Hospital, NHS Tayside, Dundee, GBR
| | - Hafsa A Osman
- Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Merna Haridi
- Medical Education, Saint Martinus University, Curacao, CUW
| | - Natalie A Gonzalez
- Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Sana M Dayo
- Obstetrics and Gynecology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Umaima Fatima
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aaiyat Sheikh
- Internal Medicine, Era's Lucknow Medical College & Hospital, Lucknow, IND
| | - Sai Sri Penumetcha
- General Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- General Medicine, Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar, IND
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PG G, Chugh A, Chaudhry K, Kaur A, Kumar P, Gaur S, Kumar S, Singh S. Comparison of Teriparatide and Combination of Cissus Quadrangularis and Dalbergia Sissoo on Bone Healing Against the Control Group in Maxillofacial Fractures: A Randomized Open-label Control Trial. Craniomaxillofac Trauma Reconstr 2023; 16:23-33. [PMID: 36824186 PMCID: PMC9941294 DOI: 10.1177/19433875211067007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Study Design Randomized Control Trial. Objective A randomized control trial was planned to aim to assess whether subcutaneous Injection of Teriparatide and Tablet Reunion (combination of Cissus Quadrangularis and Dalbergia sissoo) improves maxillofacial fracture healing as compared to the control group. Methods 24 patients of mandibular fracture with or without concomitant maxillofacial fractures were randomly divided into 3 equal groups (Group 1- Control, Group 2- Tablet Reunion, and Group 3- Injection Teriparatide) and the treatment duration was 4 weeks. Pain, fracture site mobility, bite force, serum markers, and radiographic healing were assessed preoperatively and postoperatively at regular intervals till 12 weeks. Results Group 2 showed early pain relief, although it was insignificant. Group 3 showed the highest anterior bite force at all the time points. Change in mean posterior bite force (PBF) showed a statistically significant increase at 8th week and 12th week in intergroup comparison; however, at 12th week, Group 3 was significantly better than Group 1 and reported the highest posterior bite force compared to other groups. Serum calcium and PTH level showed no significant difference, whereas Serum ALP showed a statistically significant increase in Group 3. The radiographic assessment showed no significant difference among the 3 groups. Conclusions Both the intervention group drugs showed a promising effect on accelerating the fracture healing and improving bite force restoration with the osteoanabolic action; however, early radiographic healing and increased serum osteogenic markers in Group 3 indicate its possible optimistic role in maxillofacial fracture healing.
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Affiliation(s)
- Gigi PG
- Department of Dentistry, All India Institute of Medical Sciences Jodhpur, Jodhpur, India
| | - Ankita Chugh
- Department of Dentistry, All India Institute of Medical Sciences Jodhpur, Jodhpur, India
| | - Kirti Chaudhry
- Department of Dentistry, All India Institute of Medical Sciences Jodhpur, Jodhpur, India
| | - Amanjot Kaur
- Department of Dentistry, All India Institute of Medical Sciences Jodhpur, Jodhpur, India
| | - Pravin Kumar
- Department of Dentistry, All India Institute of Medical Sciences Jodhpur, Jodhpur, India
| | - Shubham Gaur
- Department of Dentistry, All India Institute of Medical Sciences Jodhpur, Jodhpur, India
| | - Shailendra Kumar
- Department of Dentistry, All India Institute of Medical Sciences Jodhpur, Jodhpur, India
| | - Surjit Singh
- Department of Dentistry, All India Institute of Medical Sciences Jodhpur, Jodhpur, India
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Abstract
Stress fractures are a common injury that present in athletes because of the high intensity and repetitive nature of many sports. These injuries require a high index of suspicion in the treating clinician to allow for timely management. Though most low-risk fractures heal well with conservative management, high-risk stress fractures as well as any fracture in the elite athlete may warrant surgical intervention as well as an augmented treatment and rehabilitation regimen.
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Affiliation(s)
- Eric Shi
- Sutter East Bay Medical Foundation, 20101 Lake Chabot Road, Castro Valley, CA 94546, USA.
| | - Lawrence M Oloff
- Sutter Health Palo Alto Medical Foundation, Callan Boulevard, Daly City, CA 94015, USA
| | - Nicholas W Todd
- Sutter Health Palo Alto Medical Foundation, 701 East El Camino Real, Mountain View, CA 94040, USA
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Smolinska V, Csobonyeiova M, Zamborsky R, Danisovic L. Stem Cells and Their Derivatives: An Implication for the Regeneration of Nonunion Fractures. Cell Transplant 2023; 32:9636897231183530. [PMID: 37462248 PMCID: PMC10363876 DOI: 10.1177/09636897231183530] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 06/02/2023] [Accepted: 06/06/2023] [Indexed: 07/20/2023] Open
Abstract
Despite advances in biomedical research, fracture nonunion rates have remained stable throughout the years. Long-bone fractures have a high likelihood of nonunion, but the specific biological pathways involved in this severe consequence are unknown. Fractures often heal in an organized sequence, including the production of a hematoma and an early stage of inflammation, the development of a soft callus and hard callus, and eventually the stage of bone remodeling. Deficient healing can result in a persistent bone defect with instability, discomfort, and loss of function. In the treatment of nonunions, mesenchymal stem cells (MSCs) prove to be a promising and safe alternative to the standard therapeutic strategies. Moreover, novel scaffolds are being created in order to use a synergistic biomimetic technique to rapidly generate bone tissue. MSCs respond to acellular biomimetic matrices by regenerating bone. Extracellular vesicles (EVs) derived from MSCs have recently gained interest in the field of musculoskeletal regeneration. Although many of these techniques and technologies are still in the preclinical stage and have not yet been approved for use in humans, novel approaches to accelerate bone healing via MSCs and/or MSC derivatives have the potential to reduce the physical, economic, and social burdens associated with nonhealing fractures and bone defects. In this review, we focus on providing an up-to-date summary of recent scientific studies dealing with the treatment of nonunion fractures in clinical and preclinical settings employing MSC-based therapeutic techniques.
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Affiliation(s)
- Veronika Smolinska
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
- National Institute of Rheumatic Diseases, Piestany, Slovakia
| | - Maria Csobonyeiova
- National Institute of Rheumatic Diseases, Piestany, Slovakia
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
| | - Radoslav Zamborsky
- National Institute of Rheumatic Diseases, Piestany, Slovakia
- Department of Orthopaedics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
- National Institute of Children’s Diseases, Bratislava, Slovakia
- Centre for Tissue Engineering and Regenerative Medicine–Translational Research Unit, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
| | - Lubos Danisovic
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
- National Institute of Rheumatic Diseases, Piestany, Slovakia
- Centre for Tissue Engineering and Regenerative Medicine–Translational Research Unit, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
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Oh YK, Moon NH, Shin WC. Management of Osteoporosis Medication after Osteoporotic Fracture. Hip Pelvis 2022; 34:191-202. [PMID: 36601612 PMCID: PMC9763832 DOI: 10.5371/hp.2022.34.4.191] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 08/10/2022] [Indexed: 12/14/2022] Open
Abstract
The aim of this study was to provide helpful information for use in selection of an appropriate medication after osteoporotic fractures through conduct of a literature review. In addition, a review of the recommendations of several societies for prevention of subsequent fractures was performed and the appropriate choice of medication for treatment of atypical femur fractures was examined. Clinical perspective was obtained and an updated search of literature was conducted across PubMed and MEDLINE and relevant articles were selected. The articles were selected manually according to relevance, and the references for identified articles and reviews were also evaluated for relevance. The following areas are reviewed: Commonly prescribed osteoporosis medications: BPs (bisphosphonates), denosumab, and SERMs (selective estrogen receptor modulators) in antiresorptive medications and recombinant human parathyroid hormone teriparatide, recently approved Romosuzumab in anabolic agents, clinical practice guidelines for the management of osteoporosis, osteoporotic fracture, and atypical femur fracture. Most medications for treatment of osteoporosis do not delay fracture healing and the positive effect of teriparatide on fracture healing has been confirmed. In cases where an osteoporotic fracture is diagnosed, risk assessment should be performed for selection of very high-risk patients in order to prevent subsequent fractures, and administration of anabolic agents is recommended.
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Affiliation(s)
- Young Kwang Oh
- Department of Orthopaedic Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - Nam Hoon Moon
- Department of Orthopaedic Surgery, Pusan National University Hospital, Busan, Korea
| | - Won Chul Shin
- Department of Orthopaedic Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
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Saul D, Khosla S. Fracture Healing in the Setting of Endocrine Diseases, Aging, and Cellular Senescence. Endocr Rev 2022; 43:984-1002. [PMID: 35182420 PMCID: PMC9695115 DOI: 10.1210/endrev/bnac008] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Indexed: 11/19/2022]
Abstract
More than 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration of bone structure is associated with impaired bone healing. Fracture healing is a dynamic process which can be divided into four stages. While the initial hematoma generates an inflammatory environment in which mesenchymal stem cells and macrophages orchestrate the framework for repair, angiogenesis and cartilage formation mark the second healing period. In the central region, endochondral ossification favors soft callus development while next to the fractured bony ends, intramembranous ossification directly forms woven bone. The third stage is characterized by removal and calcification of the endochondral cartilage. Finally, the chronic remodeling phase concludes the healing process. Impaired fracture healing due to aging is related to detrimental changes at the cellular level. Macrophages, osteocytes, and chondrocytes express markers of senescence, leading to reduced self-renewal and proliferative capacity. A prolonged phase of "inflammaging" results in an extended remodeling phase, characterized by a senescent microenvironment and deteriorating healing capacity. Although there is evidence that in the setting of injury, at least in some tissues, senescent cells may play a beneficial role in facilitating tissue repair, recent data demonstrate that clearing senescent cells enhances fracture repair. In this review, we summarize the physiological as well as pathological processes during fracture healing in endocrine disease and aging in order to establish a broad understanding of the biomechanical as well as molecular mechanisms involved in bone repair.
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Affiliation(s)
- Dominik Saul
- Kogod Center on Aging and Division of Endocrinology, Mayo Clinic, Rochester, Minnesota 55905, USA.,Department of Trauma, Orthopedics and Reconstructive Surgery, Georg-August-University of Goettingen, 37073 Goettingen, Germany
| | - Sundeep Khosla
- Kogod Center on Aging and Division of Endocrinology, Mayo Clinic, Rochester, Minnesota 55905, USA
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32
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Costa TMDRL, Borba VZC, Correa RGP, Moreira CA. Stress fractures. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2022; 66:765-773. [PMID: 36382766 PMCID: PMC10118812 DOI: 10.20945/2359-3997000000562] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Stress fractures (SF) represent 10%-20% of all injuries in sport medicine. An SF occurs when abnormal and repetitive loading is applied on normal bone: The body cannot adapt quickly enough, leading to microdamage and fracture. The etiology is multifactorial with numerous risk factors involved. Diagnosis of SF can be achieved by identifying intrinsic and extrinsic factors, obtaining a good history, performing a physical exam, and ordering laboratory and imaging studies (magnetic resonance imaging is the current gold standard). Relative energy deficiency in sport (RED-S) is a known risk factor. In addition, for women, it is very important know the menstrual status to identify long periods of amenorrhea in the past and the present. Early detection is important to improve the chance of symptom resolution with conservative treatment. Common presentation involves complaints of localized pain, with or without swelling, and tenderness on palpation of bony structures that begins earlier in training and progressively worsens with activity over a 2- to 3-week period. Appropriate classification of SF based on type, location, grading, and low or high risk is critical in guiding treatment strategies and influencing the time to return to sport. Stress injuries at low-risk sites are typically managed conservatively. Studies have suggested that calcium and vitamin D supplementation might be helpful. Moreover, other treatment regimens are not well established. Understanding better the pathophysiology of SFs and the potential utility of current and future bone-active therapeutics may well yield approaches that could treat SFs more effectively.
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33
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Gou P, Zhao Z, Yu C, Hou X, Gao G, Zhang T, Chang F. Efficacy of Recombinant Human Parathyroid Hormone versus Vertebral Augmentation Procedure on Patients with Acute Osteoporotic Vertebral Compression Fracture. Orthop Surg 2022; 14:2510-2518. [PMID: 36017765 PMCID: PMC9531108 DOI: 10.1111/os.13470] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 07/25/2022] [Accepted: 07/26/2022] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE Although widely used in clinical practice, vertebral augmentation procedure (VAP) for osteoporotic vertebral compression fracture (OVCF) is not supported. Recently, the effect of recombinant human parathyroid hormone (1-34) (rhPTH) has been paid great attention for its efficacy in anti-osteoporosis and bone union. This study aims to explore the outcome of rhPTH on acute OVCF and compare it with VAP to clarify its therapeutic advantages. METHODS The retrospective study comprised 71 acute OVCF patients from January 2015 to March 2020: 22 received rhPTH treatment (rhPTH group) and 49 underwent VAP (VAP group). The rhPTH group was 15 women and seven men with an average of 76.18 years, and the VAP group were 35 women and 14 men with an average of 73.63 years. The thoracic/lumbar vertebrae were 14/8 in the rhPTH group and 29/20 in the VAP group. The average follow-up period was 14.05 months in the rhPTH group and 13.82 months in the VAP group. The two groups were assessed regarding the visual analog score (VAS), Oswestry Disability Index (ODI), OVCF bone union, bone mineral density (BMD), kyphotic angle (KA), anterior and posterior border height (ABH and PBH, respectively), adverse events and the health-related quality of life assessed by short form-36 health survey scores (SF-36). Categorical variables were analyzed by chi-square test and continuous variables between groups were analyzed by independent samples t-test or Mann-Whitney U test according to the normality. RESULTS During the follow-up, the VAS was significantly lower in the rhPTH group than in the VAP group at month 3 (0.39 ± 0.6 vs 0.68 ± 0.651) (p = 0.047), month 6 (0.45 ± 0.60 vs 2.18 ± 1.22) (p < 0.001), and month 12 (0.45 ± 0.60 vs 2.43 ± 1.49) (p < 0.001). At month 12, the ODI was significantly lower in the rhPTH group (18.59 ± 3.33%) than in the VAP group (28.93 ± 16.71%) (p < 0.001). Bone bridge was detected on sagittal computed tomography images of all fractured vertebrae in the rhPTH group. The BMD was significantly higher in the rhPTH group (87.66 ± 5.91 Hounsfield units [HU]) than in the VAP group (68.15 ± 11.32HU) (p < 0.001). There were no significant differences in the changes in KA, ABH, and PBH between groups (all p > 0.05). The incidence of new OVCF was significantly lower in the rhPTH group than in the VAP group (p = 0.042). All scores of SF-36 were significantly higher in the rhPTH group than in the VAP group (all p < 0.05). CONCLUSION In acute OVCF patients, rhPTH was better than VAP in increasing spinal BMD to promote OVCF healing, reduce new OVCF, and improve back pain, physical ability, and health-related quality of life.
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Affiliation(s)
- Pengguo Gou
- Department of Orthopedic SurgeryThe Fifth Affiliated Hospital of Shanxi Medical UniversityTaiyuanShanxiChina
| | - Zhihui Zhao
- Department of Orthopedic SurgeryThe Tianjin 4th Centre HospitalTianjinTianjinChina
| | - Chen Yu
- Department of Orthopedic SurgeryThe Fifth Affiliated Hospital of Shanxi Medical UniversityTaiyuanShanxiChina
| | - Xuefeng Hou
- Department of Orthopedic SurgeryThe Fifth Affiliated Hospital of Shanxi Medical UniversityTaiyuanShanxiChina
| | - Gang Gao
- Department of Orthopedic SurgeryThe Fifth Affiliated Hospital of Shanxi Medical UniversityTaiyuanShanxiChina
| | - Ting Zhang
- Department of Orthopedic SurgeryThe Fifth Affiliated Hospital of Shanxi Medical UniversityTaiyuanShanxiChina
| | - Feng Chang
- Department of Orthopedic SurgeryThe Fifth Affiliated Hospital of Shanxi Medical UniversityTaiyuanShanxiChina
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Hansen DG, Tutaworn T, Lane JM. What's New in Osteoporosis and Fragility Fractures. J Bone Joint Surg Am 2022; 104:1509-1515. [PMID: 35880771 DOI: 10.2106/jbjs.22.00530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Derek G Hansen
- Metabolic Bone Disease Service, Department of Orthopedics, Hospital for Special Surgery, New York, NY
- Department of Orthopedics, Weill Cornell Medicine, New York, NY
| | - Teerapat Tutaworn
- Metabolic Bone Disease Service, Department of Orthopedics, Hospital for Special Surgery, New York, NY
- Department of Orthopedics, Phramongkutklao Hospital, Bangkok, Thailand
| | - Joseph M Lane
- Metabolic Bone Disease Service, Department of Orthopedics, Hospital for Special Surgery, New York, NY
- Department of Orthopedics, Weill Cornell Medicine, New York, NY
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35
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Kempenaers K, Claes T, Van Beek N, Claes S. IC-Type Electric stimulation for delayed bone healing: monocentric evaluation over eight years of experience. Acta Orthop Belg 2022; 88:525-532. [PMID: 36791706 DOI: 10.52628/88.3.6890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Electrostimulation is suggested to positively influence bone healing for delayed unions of both fractures and osteotomies. This monocentric series aims to retrospectively assess the outcome of electrostimulation treatment for delayed union after traumatic fractures or knee osteotomy. Patients treated with electrostimulation for delayed union (no bony union on radiographic imaging at 90 days after osteotomy or fracture treatment) over an 8-year period were screened. The delay of treatment, success rate, revision rate and demographic data (age, sex, location of fracture, presence of osteosynthesis materials) were investigated. A questionnaire assessed objective (nicotine abuse, NRS pain assessment, activity levels) and subjective (comfort, usability, cost-effectiveness) aspects. Electrostimulation delivered radiographic healing in 75% of the fracture group and 66% of the osteotomy group. No statistical significant difference (N=136) in success rate was found for age, sex, presence of osteosynthesis material, delay or fracture location. Success rate did differ significantly with pain, activity level and smoking (p<0.05). Reflective questions to patients were answered mostly positively. The use of electrostimulation for the delayed union of fractures and knee osteotomies delivers high healing rates avoiding the burden of surgical reintervention. It is generally well received by the patient. No difference in success rate was found between sex, age or fracture location, nor did the delay of therapy onset or presence of osteosynthesis material seem to affect the success rate. Smoking had a negative influence on the efficacy of bone electrostimulation.
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Teriparatide as an Effective Nonsurgical Treatment for a Patient with Basicervical Peritrochanteric Fracture Nonunion—A Case Report. Medicina (B Aires) 2022; 58:medicina58080983. [PMID: 35893098 PMCID: PMC9330431 DOI: 10.3390/medicina58080983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/18/2022] [Accepted: 07/22/2022] [Indexed: 11/16/2022] Open
Abstract
The nonunion rate of surgically treated basicervical peritrochanteric fractures has been reported to be as high as 9%. Due to the high 1-year mortality rate following revision surgery, finding an effective nonsurgical treatment option is of interest. Over the last decade, numerous reports have been published that have suggested teriparatide as an effective treatment for certain types of fracture nonunion. However, the literature focused on teriparatide treatment for proximal femoral fracture nonunion is scanty. A 70-year-old man suffering from a left hip basicervical peritrochanteric fracture received cephalomedullary nail fixation. Nine months after the surgery, the patient still complained of left hip pain referring to the medial thigh with an antalgic limping gait. No sign of healing was noted for more than a consecutive 3 months of follow-up. Fracture nonunion was diagnosed and further confirmed by the computed tomography (CT). The patient preferred nonsurgical treatment after thorough discussion. He then received 4 months of subcutaneous teriparatide injections, 20 mcg daily. After less than 4 months of teriparatide treatment, a follow-up CT confirmed fracture union and the patient’s pain subsided. The patient also tolerated independent ambulation afterward. Teriparatide has been reported to be an effective treatment for certain types of fracture nonunion. Our case goes a step further to expand its possible application for basicervical peritrochanteric fracture nonunion. However, further larger scale studies are needed to confirm its efficacy.
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37
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Palui R, Durgia H, Sahoo J, Naik D, Kamalanathan S. Timing of osteoporosis therapies following fracture: the current status. Ther Adv Endocrinol Metab 2022; 13:20420188221112904. [PMID: 35899183 PMCID: PMC9310203 DOI: 10.1177/20420188221112904] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 06/24/2022] [Indexed: 11/23/2022] Open
Abstract
In most patients, osteoporosis is diagnosed only after the occurrence of the first fragility fracture. It is of utmost importance to start osteoporosis medications immediately in these patients to prevent future fractures and also to reduce associated mortality and morbidity. There remains a hesitancy over initiating osteoporotic medications, specifically for antiresorptive agents like bisphosphonates following an acute fracture due to concern over their effect on fracture healing. The purpose of this review is to study the effect of the timing of initiation of different osteoporosis medications on healing after an acute fracture. Most of the human studies, including randomized control trials (RCTs), did not find any significant negative effect on fracture healing with early use of bisphosphonate after an acute fracture. Anabolic agents like teriparatide have shown either neutral or beneficial effects on fracture healing and thus can be started very early following any osteoporotic fracture. Although human studies on the early use of other osteoporosis medications like denosumab or strontium ranelate are very sparse in the literature, none of these medications have shown any evidence of delay in fracture healing. To summarize, among the commonly used anti-osteoporosis agents, both bisphosphonates and teriparatide are safe to be initiated in the early acute post-fracture period. Moreover, teriparatide has shown some evidence in favor of reducing fracture healing time.
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Affiliation(s)
- Rajan Palui
- Department of Endocrinology, The Mission
Hospital, Durgapur, India
| | - Harsh Durgia
- Dr. Harsh’s Endocrine and Diabetes Center,
Rajkot, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal
Institute of Postgraduate Medical Education and Research, Puducherry,
India
| | - Dukhabandhu Naik
- Department of Endocrinology, Jawaharlal
Institute of Postgraduate Medical Education and Research, Puducherry,
India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal
Institute of Postgraduate Medical Education and Research, Puducherry 605006,
India
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Abdel Nasser Atia G, Shalaby HK, Zehravi M, Ghobashy MM, Ahmad Z, Khan FS, Dey A, Rahman MH, Joo SW, Barai HR, Cavalu S. Locally Applied Repositioned Hormones for Oral Bone and Periodontal Tissue Engineering: A Narrative Review. Polymers (Basel) 2022; 14:polym14142964. [PMID: 35890740 PMCID: PMC9319147 DOI: 10.3390/polym14142964] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 07/16/2022] [Accepted: 07/18/2022] [Indexed: 12/25/2022] Open
Abstract
Bone and periodontium are tissues that have a unique capacity to repair from harm. However, replacing or regrowing missing tissues is not always effective, and it becomes more difficult as the defect grows larger. Because of aging and the increased prevalence of debilitating disorders such as diabetes, there is a considerable increase in demand for orthopedic and periodontal surgical operations, and successful techniques for tissue regeneration are still required. Even with significant limitations, such as quantity and the need for a donor area, autogenous bone grafts remain the best solution. Topical administration methods integrate osteoconductive biomaterial and osteoinductive chemicals as hormones as alternative options. This is a promising method for removing the need for autogenous bone transplantation. Furthermore, despite enormous investigation, there is currently no single approach that can reproduce all the physiologic activities of autogenous bone transplants. The localized bioengineering technique uses biomaterials to administer different hormones to capitalize on the host’s regeneration capacity and capability, as well as resemble intrinsic therapy. The current study adds to the comprehension of the principle of hormone redirection and its local administration in both bone and periodontal tissue engineering.
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Affiliation(s)
- Gamal Abdel Nasser Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia P.O. Box 41522, Egypt
- Correspondence: (G.A.N.A.); (H.K.S.); (H.R.B.); (S.C.)
| | - Hany K. Shalaby
- Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Suez University, Suez P.O. Box 43512, Egypt
- Correspondence: (G.A.N.A.); (H.K.S.); (H.R.B.); (S.C.)
| | - Mehrukh Zehravi
- Department of Clinical Pharmacy Girls Section, Prince Sattam Bin Abdul Aziz University, Al-Kharj 11942, Saudi Arabia;
| | - Mohamed Mohamady Ghobashy
- Radiation Research of Polymer Chemistry Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, P.O. Box 8029, Cairo 13759, Egypt;
| | - Zubair Ahmad
- Unit of Bee Research and Honey Production, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia;
- Biology Department, College of Arts and Sciences, Dehran Al-Junub, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia;
| | - Farhat S. Khan
- Biology Department, College of Arts and Sciences, Dehran Al-Junub, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia;
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata 700073, India;
| | - Md. Habibur Rahman
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea;
| | - Sang Woo Joo
- School of Mechanical and IT Engineering, Yeungnam University, Gyeongsan 38541, Korea;
| | - Hasi Rani Barai
- School of Mechanical and IT Engineering, Yeungnam University, Gyeongsan 38541, Korea;
- Correspondence: (G.A.N.A.); (H.K.S.); (H.R.B.); (S.C.)
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, Piata 1 Decembrie 10, 410087 Oradea, Romania
- Correspondence: (G.A.N.A.); (H.K.S.); (H.R.B.); (S.C.)
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Hadji P, Mouzakiti N, Kyvernitakis I. Effect of Teriparatide on Subsequent Fracture and Bone Mineral Density in 47 Women with Pregnancy- and Lactation-associated Osteoporosis and Vertebral Fractures. Geburtshilfe Frauenheilkd 2022; 82:619-626. [PMID: 35903718 PMCID: PMC9315397 DOI: 10.1055/a-1816-6700] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 04/01/2022] [Indexed: 10/27/2022] Open
Abstract
Abstract
Introduction Pregnancy- and lactation-associated osteoporosis (PLO) with predominantly vertebral fractures is a rare but severe disease which can occur in the last trimester of
pregnancy or postpartum. The aim of the present study was to assess the impact of teriparatide on subsequent fractures and bone mineral density (BMD) in patients with PLO.
Materials and Methods A total of 47 patients with PLO and postpartum spinal fractures (mean: 4 fractures) undergoing treatment with teriparatide were investigated. The data
collection period was set between 2006 and 2018. All patients received a subcutaneous injection of 20 µg teriparatide once a day for 24 months as well as individually adapted vitamin D
supplementation. After 24 months of treatment, all women received no further treatment and either had regular menstrual cycles or took oral contraceptives. Fractures were confirmed by X-ray
or MRI. Changes in BMD from baseline were examined using serial DXA measurements.
Results After 24 months of teriparatide treatment, we could demonstrate an increase in BMD at the lumbar spine, femoral neck and total hip of + 30.1%, + 11.7% and + 12.2%
respectively (p < 0.001 for all). At 12 months after cessation of treatment, BMD remained stable compared to the 24-month measurements at the lumbar spine, femoral neck and total hip
which showed non-significant changes of + 1.4%, + 2.6% and + 4.1% respectively. Out of the 47 patients with PLO with a mean of 4 existing fractures, 4 patients (7.8%) sustained a subsequent
fracture, two after 3 – 5 months of treatment and two at > 6 months of treatment.
Conclusion 24 months of treatment with teriparatide in women with PLO and multiple vertebral fractures significantly increased BMD, predominantly BMD of the spine. As patients were
premenopausal, there was no significant decrease in BMD in the following 12 months after cessation of treatment.
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Affiliation(s)
- Peyman Hadji
- Frankfurt Centre for Bone Health, Frankfurt, Germany
- Philipps-University of Marburg, Marburg, Germany
| | - Niki Mouzakiti
- Dpt. of Obstetrics and Gynaecology, Centre for Ultrasound and Prenatal Medicine, Buergerhospital and Clementine Childrenʼs Hospital Frankfurt a. M., Dr. Senckenberg Foundation and
Johann-Wolfgang-Goethe University of Frankfurt, Frankfurt, Germany
| | - Ioannis Kyvernitakis
- Dpt. Of Obstetrics and Prenatal Medicine, Asklepios Clinic Barmbek, University of Semmelweis, Hamburg, Germany
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Mishra S, Satapathy D, Samal S, Zion N, Lodh U. Role of Supplemental Teriparatide Therapy to Augment Functional and Radiological Outcomes in Osteoporotic Intertrochanteric Hip Fractures in the Elderly Population. Cureus 2022; 14:e26190. [PMID: 35891832 PMCID: PMC9305672 DOI: 10.7759/cureus.26190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2022] [Indexed: 11/22/2022] Open
Abstract
With improved life expectancy and ever-increasing geriatric population with concomitant osteoporosis, there is increase in osteoporotic intertrochanteric hip fractures. Even the best surgical advances fail to provide satisfactory and early results. As a result, researchers' focus has lately shifted to developing a more integrated approach that combines the pharmacotherapeutic capabilities of teriparatide, a recombinant version of human parathyroid hormone (1-34), a new anabolic drug that enhances bone mass and strength by promoting osteoblastic activity and hastens fracture union in both human and animals. We attempted to evaluate the therapeutic efficiency of teriparatide therapy on outcomes of surgically managed Intertrochanteric hip fractures in osteoporotic patients. A total of 31 patients with established osteoporosis and Intertrochanteric fractures were selected and divided into two groups, managed surgically with proximal femur nailing, and then prospectively compared with one group receiving teriparatide therapy in addition to standard treatment after taking necessary consent and allocation into two groups based on the preference of patients to take additional teriparatide or not after understanding the benefits and risks involved. We aimed to assess the functional and radiological effects of teriparatide on bone mineral density, the time taken for fracture union, and other fracture-related postoperative complications such as weight bearing and residual bone pain. All patients were followed up at 6, 12, and 24 weeks. Time to fracture union was significantly shortened, with considerable improvement in bone density and functional outcome in the teriparatide group. Varus collapse, the rate of migration of the helical blade, and shortening of the femoral neck were also significantly less in the study group. From the assembled data, we can safely assume that with early union rates with better functional improvement with additional advantage of increased bone mass, we favor supplemental teriparatide therapy in the management of osteoporotic patients with femoral intertrochanteric fractures to augment healing. Further studies with a larger sample size are required to support our observation.
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Affiliation(s)
- Sanket Mishra
- Department of Orthopedic Surgery, Institute of Medical Sciences & SUM Hospital, Bhubaneswar, IND
| | - Deepankar Satapathy
- Department of Orthopedic Surgery, Institute of Medical Sciences & SUM Hospital, Bhubaneswar, IND
| | - Sidhartha Samal
- Department of Orthopedic Surgery, Institute of Medical Sciences & SUM Hospital, Bhubaneswar, IND
| | - Nego Zion
- Department of Orthopedic Surgery, Institute of Medical Sciences & SUM Hospital, Bhubaneswar, IND
| | - Udeepto Lodh
- Department of Orthopedic Surgery, Institute of Medical Sciences & SUM Hospital, Bhubaneswar, IND
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McClung MR, Rothman MS, Lewiecki EM, Hanley DA, Harris ST, Miller PD, Kendler DL. The role of osteoanabolic agents in the management of patients with osteoporosis. Postgrad Med 2022; 134:541-551. [DOI: 10.1080/00325481.2022.2069582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Michael R. McClung
- Oregon Osteoporosis Center, Portland, OR; Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia
| | - Micol S. Rothman
- Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | | | - David A. Hanley
- Departments of Medicine, Community Health Sciences, and Oncology, Cumming School of Medicine and McCaig Institute for Bone and Joint Health, the University of Calgary, Calgary, Alberta, Canada
| | - Steven T. Harris
- Department of Medicine, University of California, San Francisco, CA, USA
| | | | - David L. Kendler
- Department of Medicine (Endocrinology), University of British Columbia, Vancouver, British Columbia, Canada
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Ховасова НО, Дудинская ЕН, Наумов АВ, Ткачева ОН, Мачехина ЛВ, Онучина ЮС. [Effect of bone anabolic therapy on bone remodeling and bone density in geriatric patients with osteoporosis and falling syndrome]. PROBLEMY ENDOKRINOLOGII 2022; 68:67-75. [PMID: 35841170 PMCID: PMC9762541 DOI: 10.14341/probl13079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/04/2022] [Accepted: 04/04/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Older adults with severe osteoporosis are the most vulnerable group of geriatric patients. They are shown the purpose of anti-osteoporotic therapy, which should be effective and safe. Teriparatide showed a decrease in the risk of fractures, an increase in BMD. In Russia, the use of teriparatide in the geriatric population is extremely scarce. AIM assess clinical course, bone metabolism parameters and efficacy of bone-anabolic therapy in elderly and senile patients with severe osteoporosis and falls. MATERIALS AND METHODS The longitudinal prospective study included 100 patients 60 years and older with severe osteoporosis who had one or more falls within the last year. All patients were prescribed calcium and vitamin D preparations and bone-anabolic therapy (teriparatide 20 mg daily subcutaneously). The duration of follow-up was 24 months and included 3 visits: screening, at 12 and 24 months. The effectiveness of bone-anabolic therapy was carried out on the basis of assessing the frequency of new fractures, reduction of pain, changes in BMD according to X-ray densitometry, dynamics of bone metabolism markers. RESULTS All patients had severe osteoporosis and aggravated comorbidity status, suffered a fall within the last year, and also low-energy fractures in the past. One in three patients had a vertebral fracture, one in five had a proximal femoral fracture. Prior to the start of the study, 61 patients received antiosteoporotic therapy. During the follow-up, 4 patients died, 96 patients completed the study. Against the background of teriparatide therapy, a decrease in the number of new cases of low-energy fractures and the number of patients with chronic pain was obtained. An increase in BMD was noted in the lumbar spine after 24 months and in the femoral neck after 12 months. There was no negative dynamics of the BMD. Also after 12 months, an increase in P1NP and C-terminal telopeptide of collagen type 1 was noted, after 24 months - osteocalcin and C-terminal telopeptide. CONCLUSION The use of teriparatide can be recommended as an effective intervention to treat severe osteoporosis in geriatric patients with falls.
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Affiliation(s)
- Н. О. Ховасова
- Кафедра болезней старения, Российский национальный исследовательский медицинский университет им. Пирогова; Лаборатория заболеваний костно-мышечной системы, Российский геронтологический научно-клинический центр
| | - Е. Н. Дудинская
- Кафедра болезней старения, Российский национальный исследовательский медицинский университет им. Пирогова; Лаборатория возрастных метаболических и эндокринных нарушений, Российский геронтологический научноклинический центр
| | - А. В. Наумов
- Кафедра болезней старения, Российский национальный исследовательский медицинский университет им. Пирогова; Лаборатория заболеваний костно-мышечной системы, Российский геронтологический научно-клинический центр
| | - О. Н. Ткачева
- Кафедра болезней старения, Российский национальный исследовательский медицинский университет им. Пирогова
| | - Л. В. Мачехина
- Кафедра болезней старения, Российский национальный исследовательский медицинский университет им. Пирогова; Лаборатория возрастных метаболических и эндокринных нарушений, Российский геронтологический научноклинический центр
| | - Ю. С. Онучина
- Кафедра болезней старения, Российский национальный исследовательский медицинский университет им. Пирогова; Лаборатория возрастных метаболических и эндокринных нарушений, Российский геронтологический научноклинический центр
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Sakuda T, Omoto O, Hamasaki T, Okimoto N, Adachi N. Incomplete Atypical Femoral Fracture Treated by Prophylactic Intramedullary Nail Fixation: A Case Series. Cureus 2022; 14:e22725. [PMID: 35386143 PMCID: PMC8968090 DOI: 10.7759/cureus.22725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/28/2022] [Indexed: 11/15/2022] Open
Abstract
Long-term bisphosphonate use may be associated with atypical femoral fractures. In this report, we describe three cases of bisphosphonate-associated incomplete atypical femoral fracture, treated by prophylactic intramedullary nail fixation. Patients with long-term intake of bisphosphonates must be carefully monitored; atypical femoral fracture should be suspected in the presence of symptoms such as thigh pain. Its early identification is important to avoid a complete fracture and invasive surgery, and prophylactic fixation is recommended for incomplete atypical femoral fractures.
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Nieves JW, Cosman F, McMahon D, Redko M, Hentschel I, Bartolotta R, Loftus M, Kazam JJ, Rotman J, Lane J. Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial. Osteoporos Int 2022; 33:239-250. [PMID: 34383100 PMCID: PMC8758515 DOI: 10.1007/s00198-021-06065-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 07/08/2021] [Indexed: 01/03/2023]
Abstract
UNLABELLED Pelvic fracture patients were randomized to blinded daily subcutaneous teriparatide (TPTD) or placebo to assess healing and functional outcomes over 3 months. With TPTD, there was no evidence of improved healing by CT or pain reduction; however, physical performance improved with TPTD but not placebo (group difference p < 0.03). INTRODUCTION To determine if teriparatide (20 μg/day; TPTD) results in improved radiologic healing, reduced pain, and improved functional outcome vs placebo over 3 months in pelvic fracture patients. METHODS This randomized, placebo-controlled study enrolled 35 patients (women and men >50 years old) within 4 weeks of pelvic fracture and evaluated the effect of blinded TPTD vs placebo over 3 months on fracture healing. Fracture healing from CT images at 0 and 3 months was assessed as cortical bridging using a 5-point scale. The numeric rating scale (NRS) for pain was administered monthly. Physical performance was assessed monthly by Continuous Summary Physical Performance Score (based on 4 m walk speed, timed repeated chair stands, and balance) and the Timed Up and Go (TUG) test. RESULTS The mean age was 82, and >80% were female. The intention to treat analysis showed no group difference in cortical bridging score, and 50% of fractures in TPTD-treated and 53% of fractures in placebo-treated patients were healed at 3 months, unchanged after adjustment for age, sacral fracture, and fracture displacement. Median pain score dropped significantly in both groups with no group differences. Both CSPPS and TUG improved in the teriparatide group, whereas there was no improvement in the placebo group (group difference p < 0.03 for CSPPS at 2 and 3 months). CONCLUSION In this small randomized, blinded study, there was no improvement in radiographic healing (CT at 3 months) or pain with TPTD vs placebo; however, there was improved physical performance in TPTD-treated subjects that was not evident in the placebo group.
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Affiliation(s)
- J W Nieves
- Hospital for Special Surgery, New York, NY, USA.
- Department of Epidemiology, Columbia University, New York, NY, USA.
| | - F Cosman
- Department of Medicine, Columbia University, New York, NY, USA
| | - D McMahon
- Hospital for Special Surgery, New York, NY, USA
| | - M Redko
- Hospital for Special Surgery, New York, NY, USA
| | - I Hentschel
- Hospital for Special Surgery, New York, NY, USA
| | - R Bartolotta
- Department of Radiology, University of Colorado School of Medicine, Aurora, CO, USA
| | - M Loftus
- Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - J J Kazam
- Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - J Rotman
- Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - J Lane
- Hospital for Special Surgery, New York, NY, USA
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Kim JW, Kwak MK, Han JJ, Lee ST, Kim HY, Kim SH, Jung J, Lee JK, Lee YK, Kwon YD, Kim DY. Medication Related Osteonecrosis of the Jaw: 2021 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons. J Bone Metab 2021; 28:279-296. [PMID: 34905675 PMCID: PMC8671025 DOI: 10.11005/jbm.2021.28.4.279] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 11/15/2021] [Indexed: 12/27/2022] Open
Abstract
Antiresorptives are the most widely prescribed drugs for the treatment of osteoporosis. They are also used in malignant bone metastases, multiple myeloma, and Paget's disease, and provide therapeutic efficacy on those diseases. However, it was reported that the occurrence of osteonecrosis of the jaw (ONJ) could be related to antiresorptive exposures, and there have been many cases regarding this issue. Therefore, a clearer definition and treatment guidelines were needed for this disease. The American Society for Bone and Mineral Research and the Amnerican Association of Oral and Maxillofacial Surgeons reported statements on bisphosphonate-related ONJ (BRONJ), and a revised version was recently presented. In the revised edition, the diagnosis BRONJ was changed to medication-related ONJ (MRONJ), which reflects consideration of the fact that ONJ also occurs for denosumab, a bone resorption inhibitor of the receptor activator of the nuclear factor-κB ligand antibody family, and bevacizumab, an anti-angiogenesis inhibitor. The Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons had collectively formed a task force for the preparation of an official statement on MRONJ based on a previous position paper in 2015. The task force reviewed current knowledge and coordinated dental and medical opinions to propose the guideline customized for the local Korean situation.
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Affiliation(s)
- Jin-Woo Kim
- Department of Oral and Maxillofacial Surgery, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Mi Kyung Kwak
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Jeong Joon Han
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Dental Research Institute, Seoul National University, Seoul, Korea
| | - Sung-Tak Lee
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, Korea
| | - Ha Young Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Se Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Junho Jung
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Korea
| | - Jeong Keun Lee
- Department of Oral and Maxillofacial Surgery, Institute of Oral Health Science, Ajou University Dental Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Young-Kyun Lee
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yong-Dae Kwon
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Korea
| | - Deog-Yoon Kim
- Department of Nuclear Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Korea
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Osagie-Clouard L, Meeson R, Sanghani-Kerai A, Bostrom M, Briggs T, Blunn G. The role of intermittent PTH administration in conjunction with allogenic stem cell treatment to stimulate fracture healing. Bone Joint Res 2021; 10:659-667. [PMID: 34634923 PMCID: PMC8559967 DOI: 10.1302/2046-3758.1010.bjr-2019-0371.r2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Aims A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667.
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Affiliation(s)
| | | | | | | | | | - Gorden Blunn
- School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
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Stress Fractures of the Foot and Ankle. OPER TECHN SPORT MED 2021. [DOI: 10.1016/j.otsm.2021.150852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Ishizu H, Arita K, Terkawi MA, Shimizu T, Iwasaki N. Risks vs. benefits of switching therapy in patients with postmenopausal osteoporosis. Expert Rev Endocrinol Metab 2021; 16:217-228. [PMID: 34310233 DOI: 10.1080/17446651.2021.1956902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 07/14/2021] [Indexed: 10/20/2022]
Abstract
Introduction: Osteoporosis is characterized by the fragility of bones, leading to fractures and, consequently, the deterioration of functional capacity and quality of life. Postmenopausal women, in particular, are prone to osteoporosis and often require anti-osteoporosis treatment. In the last few decades, various anti-osteoporosis drugs have been approved for clinical use. In an aging society, osteoporosis cannot be treated using a single agent; therefore, switching therapy is an important treatment strategy.Areas covered: This review covers switching therapy in patients with postmenopausal osteoporosis. It's extremely important to understand the characteristics of each drug including; limitations on the duration of use, side effects due to long-term use (such as atypical femur fracture and osteonecrosis of the jaw) or discontinuation (such as rebound phenomenon), compliance, and ability to prevent fractures. We review and summarize the risks and benefits of switching therapy.Expert opinion: When switching therapy, the order of drug administration is important. Routine monitoring should be continued after switching treatments. We recommend first using osteoanabolic agents in postmenopausal women with severe osteoporosis. In addition, identifying predictors of the efficacy and side effects of treatment may help prevent the inappropriate use of drugs for the treatment of osteoporosis.
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Affiliation(s)
- Hotaka Ishizu
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan
| | - Kosuke Arita
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan
| | - Mohamad Alaa Terkawi
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan
| | - Tomohiro Shimizu
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan
| | - Norimasa Iwasaki
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan
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The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies. Bone Rep 2021; 15:101117. [PMID: 34458509 PMCID: PMC8379440 DOI: 10.1016/j.bonr.2021.101117] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/25/2021] [Accepted: 08/10/2021] [Indexed: 01/08/2023] Open
Abstract
Introduction Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone structure. Its treatment is directed at the processes of bone formation or resorption, that are of utmost importance in fracture healing. We provide a comprehensive review of the literature aiming to summarize and clarify the effects of osteoporosis and its treatment on fracture healing. Material and methods A literature search was conducted in PubMed and Embase (OVID version). In vivo animal and human studies on long bone fractures were included. A total of 93 articles were included for this review; 23 studies on the effect of osteoporosis (18 animal and 5 clinical studies) and 70 studies on the effect of osteoporosis treatment (41 animal, 26 clinical studies and 3 meta-analyses) on fracture healing. Results In animal fracture models osteoporosis was associated with decreased callus formation and bone growth, bone mineral density, biomechanical strength and delayed cellular and differentiation processes during fracture healing. Two large databases identified osteoporosis as a risk factor for non-union whereas three other studies did not. One of those three studies however found a prolonged healing time in patients with osteoporosis. Anti-osteoporosis medication showed inconsistent effects on fracture healing in both non-osteoporotic and osteoporotic animal models. Only the parathyroid hormone and anti-resorption medication were related to improved fracture healing and delayed remodelling respectively. Clinical studies performed in predominantly hip and distal radius fracture patients showed no effect of bisphosphonates on fracture healing. Parathyroid hormone reduced time to union in several clinical trials performed in mainly hip fracture patients, but this did not result in decreased delayed or non-union rates. Conclusion Evidence that substantiates the negative influence of osteoporosis on fracture healing is predominantly from animal studies and to a lesser extent from clinical studies, since convincing clinical evidence lacks. Bisphosphonates and parathyroid hormone may be used during fracture healing, since no clear negative effect has been shown. Parathyroid hormone might even decrease time to fracture union, without decreasing union rate.
Osteoporosis negatively influences fracture healing in animal models. There is no convincing evidence for a similar effect in humans. In animals, bisphosphonates delay bone remodelling In animals, parathyroid hormone improves fracture healing In humans, anti-osteoporotic drugs do not interfere with fracture healing.
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Carswell AT, Eastman KG, Casey A, Hammond M, Shepstone L, Payerne E, Toms AP, MacKay JW, Swart AM, Greeves JP, Fraser WD. Teriparatide and stress fracture healing in young adults (RETURN - Research on Efficacy of Teriparatide Use in the Return of recruits to Normal duty): study protocol for a randomised controlled trial. Trials 2021; 22:580. [PMID: 34461961 PMCID: PMC8404180 DOI: 10.1186/s13063-021-05556-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 08/19/2021] [Indexed: 01/14/2023] Open
Abstract
Background Stress fractures are a common and potentially debilitating overuse injury to bone and occur frequently among military recruits and athletes. Recovery from a lower body stress fracture typically requires several weeks of physical rehabilitation. Teriparatide, a recombinant form of the bioactive portion of parathyroid hormone (1–34 amino acids), is used to treat osteoporosis, prevent osteoporotic fractures, and enhance fracture healing due to its net anabolic effect on bone. The study aim is to investigate the effect of teriparatide on stress fracture healing in young, otherwise healthy adults undergoing military training. Methods In a two-arm, parallel, prospective, randomised controlled, intention-to-treat trial, Army recruits (n = 136 men and women, 18–40 years) with a magnetic resonance imaging (MRI) diagnosed lower body stress fracture (pelvic girdle, sacrum, coccyx, or lower limb) will be randomised to receive either usual Army standard care, or teriparatide and usual Army standard care. Teriparatide will be self-administered by subcutaneous injections (20 μg/day) for 16 weeks, continuing to 24 weeks where a fracture remains unhealed at week 16. The primary outcome will be the improvement in radiological healing by two grades or more, or reduction to grade zero, 8 weeks after randomisation, assessed using Fredericson grading of MRI by radiologists blind to the randomisation. Secondary outcomes will be time to radiological healing, assessed by MRI at 8, 10, 12, 14, 16, 20 and 24 weeks, until healed; time to clinical healing, assessed using a clinical severity score of injury signs and symptoms; time to discharge from Army physical rehabilitation; pain, assessed by visual analogue scale; health-related quality of life, using the Short Form (36) Health Survey; and adverse events. Exploratory outcomes will include blood and urine biochemistry; bone density and morphology assessed using dual-energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), and high-resolution pQCT; physical activity measured using accelerometers; and long-term future fracture rate. Discussion This study will evaluate whether teriparatide, in addition to standard care, is more effective for stress fracture healing than standard care alone in Army recruits who have sustained a lower body stress fracture. Trial registration ClinicalTrials.govNCT04196855. Registered on 12 December 2019.
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Affiliation(s)
- Alexander T Carswell
- Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.
| | - Katharine G Eastman
- Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Anna Casey
- Army Health and Performance Research, British Army Headquarters, Ministry of Defence, Andover, SP11 8HT, UK
| | - Matthew Hammond
- Norwich Clinical Trials Unit, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Lee Shepstone
- Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.,Norwich Clinical Trials Unit, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Estelle Payerne
- Norwich Clinical Trials Unit, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Andoni P Toms
- Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK
| | - James W MacKay
- Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Ann Marie Swart
- Norwich Clinical Trials Unit, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Julie P Greeves
- Army Health and Performance Research, British Army Headquarters, Ministry of Defence, Andover, SP11 8HT, UK
| | - William D Fraser
- Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.,Departments of Endocrinology and Clinical Biochemistry, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, NR4 7UY, UK
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