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Kojima Y, Watanabe T, Mizuki F, Izumo N, Nishimura Y. Low-Intensity Pulsed Ultrasound Maintains Bone Mass After Withdrawal of Human Parathyroid Hormone in Ovariectomized Mice. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2024; 43:385-395. [PMID: 37994205 DOI: 10.1002/jum.16371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 08/11/2023] [Accepted: 10/30/2023] [Indexed: 11/24/2023]
Abstract
The intermittent injection of teriparatide, a recombinant fragment of human parathyroid hormone (PTH 1-34), activates anabolic activity on bone turnover. However, the PTH administration period is limited to 2 years. Thus, sequential therapy after discontinuation of PTH is required. Low-intensity pulsed ultrasound (LIPUS) has been widely used for bone fracture healing. In this study, we examined the effects of LIPUS on bone mass after PTH withdrawal in ovariectomized (OVX) model mice. The LIPUS-non-irradiated femoral trabecular bone mineral density (BMD) in the treated after PTH withdrawal was significantly decreased. Meanwhile, the femoral BMD in the OVX + PTH-LIPUS group was remarkably higher than that of the OVX group. Additionally, mRNA expression of Runx2, Osterix, Col1a1, and ALP increased significantly following LIPUS irradiation after PTH withdrawal. These results suggest that LIPUS protected against femoral trabecular BMD loss and up-regulated the osteogenic factors following PTH withdrawal in OVX mice.
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Affiliation(s)
- Yoshitsugu Kojima
- Clinical Pharmacology Research Laboratory, Yokohama University of Pharmacy, Yokohama, Kanagawa, Japan
- Planning and Product Development Division, Nippon Sigmax Co., Ltd., Shinjuku-ku, Tokyo, Japan
| | - Takayuki Watanabe
- Clinical Pharmacology Research Laboratory, Yokohama University of Pharmacy, Yokohama, Kanagawa, Japan
- Planning and Product Development Division, Nippon Sigmax Co., Ltd., Shinjuku-ku, Tokyo, Japan
| | - Fumitaka Mizuki
- Planning and Product Development Division, Nippon Sigmax Co., Ltd., Shinjuku-ku, Tokyo, Japan
| | - Nobuo Izumo
- General Health Medical Research Center, Yokohama University of Pharmacy, Yokohama, Kanagawa, Japan
- Laboratory of Pharmacotherapy, Yokohama University of Pharmacy, Yokohama, Kanagawa, Japan
| | - Yoshihiro Nishimura
- Planning and Product Development Division, Nippon Sigmax Co., Ltd., Shinjuku-ku, Tokyo, Japan
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Weiss SG, Kuchar GO, Gerber JT, Tiboni F, Storrer CLM, Casagrande TC, Giovanini AF, Scariot R. Dose of alendronate directly increases trabeculae expansivity without altering bone volume in rat femurs. World J Orthop 2018; 9:190-197. [PMID: 30364827 PMCID: PMC6198290 DOI: 10.5312/wjo.v9.i10.190] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Revised: 06/20/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the effects of sodium alendronate on bone repair in fractures created in appendicular bones.
METHODS Wistar rats (n = 36) were allocated into three distinct groups: group C (control), group B1 (received 1 mg/kg of alendronate), and group B2 (received 3 mg/kg of alendronate). The rats underwent femoral transversal linear fracture surgery using stable internal fixation with a 2.0 mm plate and screw system. Each animal randomly received intraperitoneal applications of sodium alendronate at a dose corresponding to group B1 or B2 three times a week, while the control group received a 0.9% saline solution. Drug administration was performed until euthanasia at 45 d. The femurs were removed and each surgical piece was sent for radiographic, tomographic and microtomographic analysis. Data were submitted to descriptive and inferential statistical analysis (95% confidence interval).
RESULTS Quantitative evaluations of bone neoformation did not show differences among the groups in the radiographic (P = 0.341), microtomographic (P = 0.581) and tomographic evaluations (P = 0.171). In the qualitative microtomographic analysis, a smaller distance was observed between the internal bone trabeculae in the groups that used alendronate (P = 0.05). On the other hand, group B2 had a higher amount of bone trabeculae per unit length when compared to the other groups (P = 0.04).
CONCLUSION It is likely that the use of alendronate did not have a direct influence on the amount of bone neoformation, however it did influence the bone quality in a dose-dependent manner, ultimately affecting the distance and quantity of the trabeculae.
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Affiliation(s)
- Suyany G Weiss
- School of Health Science, Department of Dentistry, Positivo University, Curitiba, Paraná 81280-330, Brazil
| | - Gabrielle O Kuchar
- School of Health Science, Department of Dentistry, Positivo University, Curitiba, Paraná 81280-330, Brazil
| | - Jennifer T Gerber
- School of Health Science, Department of Dentistry, Positivo University, Curitiba, Paraná 81280-330, Brazil
| | - Fernanda Tiboni
- School of Health Science, Department of Dentistry, Positivo University, Curitiba, Paraná 81280-330, Brazil
| | - Carmen Lucia M Storrer
- School of Health Science, Department of Dentistry, Positivo University, Curitiba, Paraná 81280-330, Brazil
| | - Thaís C Casagrande
- School of Health Science, Department of Biotecnology, Positivo University, Curitiba, Paraná 81280-330, Brazil
| | - Allan F Giovanini
- School of Health Science, Department of Dentistry, Positivo University, Curitiba, Paraná 81280-330, Brazil
| | - Rafaela Scariot
- School of Health Science, Department of Dentistry, Positivo University, Curitiba, Paraná 81280-330, Brazil
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Kieves NR, Canapp SO, Lotsikas PJ, Christopher SA, Leasure CS, Canapp D, Gavin PR. Effects of low-intensity pulsed ultrasound on radiographic healing of tibial plateau leveling osteotomies in dogs: a prospective, randomized, double-blinded study. Vet Surg 2018; 47:614-622. [DOI: 10.1111/vsu.12798] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 12/01/2017] [Accepted: 02/07/2018] [Indexed: 11/27/2022]
Affiliation(s)
- Nina R. Kieves
- Veterinary Orthopedic and Sports Medicine Group; Annapolis Junction Maryland
| | - Sherman O. Canapp
- Veterinary Orthopedic and Sports Medicine Group; Annapolis Junction Maryland
| | - Peter J. Lotsikas
- Veterinary Orthopedic and Sports Medicine Group; Annapolis Junction Maryland
| | | | | | - Debra Canapp
- Veterinary Orthopedic and Sports Medicine Group; Annapolis Junction Maryland
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Kawano T, Miyakoshi N, Kasukawa Y, Hongo M, Tsuchie H, Sato C, Fujii M, Suzuki M, Akagawa M, Ono Y, Yuasa Y, Nagahata I, Shimada Y. Effects of combined therapy of alendronate and low-intensity pulsed ultrasound on metaphyseal bone repair after osteotomy in the proximal tibia of glucocorticoid-induced osteopenia rats. Osteoporos Sarcopenia 2017; 3:185-191. [PMID: 30775528 PMCID: PMC6372826 DOI: 10.1016/j.afos.2017.11.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 10/15/2017] [Accepted: 11/05/2017] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVES Glucocorticoid (GC) treatment inhibits activation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation from stem cells. As a result, GC treatment results in bone loss, GC-induced osteoporosis (GIO), elevated fracture risk, and delayed bone healing. Bisphosphonates such as alendronate (ALN) are recommended for treating or preventing GIO, and low-intensity pulsed ultrasound (LIPUS) facilitates fracture healing and maturation of regenerated bone. Combined therapy with ALN and LIPUS may stimulate cancellous bone healing in GIO rats. Here, we examined the effect of ALN and LIPUS on cancellous bone osteotomy repair in the proximal tibia of GIO rats. METHODS Prednisolone (10 mg/kg body weight/day) was administered for 4 weeks to induce GIO in 6-month-old female Sprague-Dawley rats. Tibial osteotomy was then performed and daily subcutaneous injection of ALN (1-μg/kg body weight) was subsequently administered alone or in combination with LIPUS (20 min/day) for 2 or 4 weeks. RESULTS ALN significantly increased bone mineral density (BMD) at 2 and 4 weeks, and ALN + LIPUS significantly increased BMD at 4 weeks. Bone union rates were significantly increased after 2 and 4 weeks ALN and ALN + LIPUS treatment. Lastly, ALN and ALN + LIPUS significantly increased the proportion of Runx2 positive cells at 4 weeks. CONCLUSIONS ALN monotherapy and combined ALN and LUPUS treatment augmented BMD and stimulated cancellous bone repair with increased Runx2 expression at the osteotomy site in GIO rats. However, the combined treatment had no additional effect on cancellous bone healing compared to ALN monotherapy.
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Affiliation(s)
| | - Naohisa Miyakoshi
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan
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Mostafavinia A, Ahadi R, Abdollahifar M, Ghorishi SK, Jalalifirouzkouhi A, Bayat M. Evaluation of the Effects of Photobiomodulation on Biomechanical Properties and Hounsfield Unit of Partial Osteotomy Healing in an Experimental Rat Model of Type I Diabetes and Osteoporosis. Photomed Laser Surg 2017; 35:520-529. [DOI: 10.1089/pho.2016.4191] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Affiliation(s)
- Ataroalsadat Mostafavinia
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Ahadi
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammadamin Abdollahifar
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | - Mohammad Bayat
- Celluar and Molecular Biology Research Centre, and Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Haffner-Luntzer M, Liedert A, Ignatius A. Mechanobiology of bone remodeling and fracture healing in the aged organism. Innov Surg Sci 2016; 1:57-63. [PMID: 31579720 PMCID: PMC6753991 DOI: 10.1515/iss-2016-0021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 10/14/2016] [Indexed: 01/18/2023] Open
Abstract
Bone can adapt to changing load demands by mechanically regulated bone remodeling. Osteocytes, osteoblasts, and mesenchymal stem cells are mechanosensitive and respond to mechanical signals through the activation of specific molecular signaling pathways. The process of bone regeneration after fracture is similarly and highly regulated by the biomechanical environment at the fracture site. Depending on the tissue strains, mesenchymal cells differentiate into fibroblasts, chondrocytes, or osteoblasts, determining the course and the success of healing. In the aged organism, mechanotransduction in both intact and fractured bones may be altered due to changed hormone levels and expression of growth factors and other signaling molecules. It is proposed that altered mechanotransduction may contribute to disturbed healing in aged patients. This review explains the basic principles of mechanotransduction in the bone and the fracture callus and summarizes the current knowledge on aging-induced changes in mechanobiology. Furthermore, the methods for external biomechanical stimulation of intact and fractured bones are discussed with respect to a possible application in the elderly patient.
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Affiliation(s)
- Melanie Haffner-Luntzer
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, 89081 Ulm, Germany
| | - Astrid Liedert
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, 89081 Ulm, Germany
| | - Anita Ignatius
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, 89081 Ulm, Germany
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