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1
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Chatzopoulos GS, Wolff LF. Effect of antiplatelet and anticoagulant medications on implant survival: a long-term retrospective cohort study. Oral Maxillofac Surg 2025; 29:43. [PMID: 39847193 PMCID: PMC11759461 DOI: 10.1007/s10006-025-01341-7] [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: 08/22/2024] [Accepted: 01/14/2025] [Indexed: 01/24/2025]
Abstract
PURPOSE This large-scale retrospective study aimed to examine the long-term effect of antiplatelet and anticoagulant medications intake on dental implant treatment outcome. MATERIALS AND METHODS This study retrospectively examined data from patients who underwent dental implant procedures at several university dental clinics within the BigMouth network between 2011 and 2022. Patients' characteristics including age, gender, ethnicity, race, tobacco use, systemic medical conditions and intake of antiplatelets and anticoagulants were analyzed. Implant treatment outcome was the main outcome variable. Implant failure was defined as the removal of a dental implant for any reason. Time to failure (date of procedure to date of visit with failure) was recorded, while sites without a failure were censored at the last follow-up visit. RESULTS A total of 50,333 dental implants in 20,842 patients over 12 years were analyzed and an implant failure rate of 1.4% at the implant level and 2.7% at the patient level were found. Asians, African-Americans, American Indians or Alaskan Natives, and White individuals were significantly more likely to receive antiplatelet medications than Hispanics or Latinos. Males and smokers exhibited significantly higher odds of being antiplatelet and anticoagulant users compared to females and non-smokers, respectively. When the implant survival rates between antiplatelet and anticoagulant users were compared to non-users, no significant differences were observed. CONCLUSION Within the limitations of this study, it appears that the use of anticoagulant and antiplatelet medications does not affect the risk of implant failure. Both anticoagulant and antiplatelet users and non-users exhibit similar high implant survival rates.
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Affiliation(s)
- Georgios S Chatzopoulos
- Department of Developmental and Surgical Sciences, Division of Periodontology, School of Dentistry, University of Minnesota, 515 Delaware Street SE, Minneapolis, MN, 55455, USA.
- Department of Preventive Dentistry, Periodontology and Implant Biology, School of Dentistry, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
| | - Larry F Wolff
- Department of Developmental and Surgical Sciences, Division of Periodontology, School of Dentistry, University of Minnesota, 515 Delaware Street SE, Minneapolis, MN, 55455, USA
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2
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Bostan SA, Özarslantürk S, Günaçar DN, Gonca M, Göller Bulut D, Ok Bostan H. Direct-Acting Oral Anticoagulant/Vitamin K Antagonists: Do They Affect the Trabecular and Cortical Structure of the Mandible? J Clin Densitom 2024; 27:101495. [PMID: 38688206 DOI: 10.1016/j.jocd.2024.101495] [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: 02/23/2024] [Revised: 04/05/2024] [Accepted: 04/08/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND This study aimed to evaluate the mandibular bone structure of patients using oral anticoagulants (OACs) vitamin K antagonist drugs (warfarin) and other OACs including direct oral anticoagulants [(DOACs) apixaban, rivaroxaban, dabigatran, edoxaban]. Analyses were based upon the fractal dimension (FD), the panoramic mandibular index (PMI) and the Klemetti index (KI), which is also known as the mandibular cortical index (MCI). METHODOLOGY Ninety participants were divided into three groups: group 1: 30 systemically healthy individuals who had not used any anticoagulants before, group 2: 30 individuals using warfarin, and group 3: 30 individuals using DOACs. FD was used to analyze trabecular bone architecture in the condyle, angle, and two sites in the alveolar bone. PMI was used to evaluate the quantity of cortical bone and KI was used to evaluate the cortical bone quality. RESULTS There was no difference between the groups regarding FD analysis and KI; however, a difference was found between groups 1, 2, and 3 in the PMI (P≤ 0.001). The PMI in group 1 was higher than in groups 2 and 3. CONCLUSION Mandibular radiomorphometric indices can be used on panoramic radiographs to evaluate the quantity of mandibular cortical bone in patients using oral anticoagulants.
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Affiliation(s)
- Semih Alperen Bostan
- Recep Tayyip Erdoğan University, Faculty of Dentistry, Department of Periodontology, Rize, Turkey
| | - Savaş Özarslantürk
- University of Health Sciences, Gulhane Faculty of Dental Medicine, Department of Dentomaxillofacial Radiology, Ankara, Turkey
| | - Dilara Nil Günaçar
- Recep Tayyip Erdoğan University, Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Rize, Turkey
| | - Merve Gonca
- Recep Tayyip Erdoğan University, Faculty of Dentistry, Department of Orthodontics, Rize, Turkey
| | - Duygu Göller Bulut
- Bolu Abant İzzet Baysal University, Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Bolu, Turkey
| | - Hilal Ok Bostan
- Recep Tayyip Erdoğan University, Faculty of Dentistry, Department of Prosthodontics, Rize, Turkey.
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3
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Jørgensen HS, Lloret MJ, Lalayiannis AD, Shroff R, Evenepoel P. Ten tips on how to assess bone health in patients with chronic kidney disease. Clin Kidney J 2024; 17:sfae093. [PMID: 38817914 PMCID: PMC11137676 DOI: 10.1093/ckj/sfae093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Indexed: 06/01/2024] Open
Abstract
Patients with chronic kidney disease (CKD) experience a several-fold increased risk of fracture. Despite the high incidence and the associated excess morbidity and premature mortality, bone fragility in CKD, or CKD-associated osteoporosis, remains a blind spot in nephrology with an immense treatment gap. Defining the bone phenotype is a prerequisite for the appropriate therapy of CKD-associated osteoporosis at the patient level. In the present review, we suggest 10 practical 'tips and tricks' for the assessment of bone health in patients with CKD. We describe the clinical, biochemical, and radiological evaluation of bone health, alongside the benefits and limitations of the available diagnostics. A bone biopsy, the gold standard for diagnosing renal bone disease, is invasive and not widely available; although useful in complex cases, we do not consider it an essential component of bone assessment in patients with CKD-associated osteoporosis. Furthermore, we advocate for the deployment of multidisciplinary expert teams at local, national, and potentially international level. Finally, we address the knowledge gaps in the diagnosis, particularly early detection, appropriate "real-time" monitoring of bone health in this highly vulnerable population, and emerging diagnostic tools, currently primarily used in research, that may be on the horizon of clinical practice.
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Affiliation(s)
- Hanne Skou Jørgensen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark
- Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Maria Jesús Lloret
- Department of Nephrology, Hospital Fundació Puigvert, Barcelona, Spain
- Institut de Recerca Sant-Pau (IR-Sant Pau), Barcelona, Spain
| | - Alexander D Lalayiannis
- Department of Pediatric Nephrology, Birmingham Women's and Children's Hospitals, Birmingham, UK
| | - Rukshana Shroff
- Renal Unit, UCL Great Ormond Street Hospital and Institute of Child Health, London, UK
| | - Pieter Evenepoel
- Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Katholieke Universiteit Leuven, Leuven, Belgium
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
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4
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Szulc P, Lewis JR, Chapurlat R. Accelerated Bone Loss in Older Men With Severe Abdominal Aortic Calcification-the Prospective MINOS Study. J Clin Endocrinol Metab 2023; 109:e32-e39. [PMID: 37610245 DOI: 10.1210/clinem/dgad459] [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: 06/05/2023] [Revised: 06/30/2023] [Accepted: 08/07/2023] [Indexed: 08/24/2023]
Abstract
CONTEXT Data on the association between the severity of abdominal aortic calcification (AAC) and bone loss are discordant. OBJECTIVE Our aim was to assess the association between baseline AAC and prospectively assessed bone loss in older men. METHODS This prospective cohort study started in 1995 (MINOS). Men aged 50 to 85 years (n = 778) had AAC assessed on the lateral radiograph of the spine using Kauppila's semiquantitative score and was followed prospectively for 7.5 years. Bone mineral density (BMD) and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry every 18 months. Statistical analysis was performed using linear mixed models. RESULTS In comparison to men without AAC (AAC = 0), severe AAC (>6) was associated with more rapid bone loss at the total hip (-0.62 ± 0.06 vs -0.32 ± 0.04%/year; P < .001), trochanter, and distal forearm (-0.72 ± 0.06 vs -0.45 ± 0.03%/year; P < .001). The highest decile (AAC >10) was associated with more rapid bone loss at the femoral neck, whole body, and ultradistal radius (-0.86 ± 0.12 vs -0.34 ± 0.05%/year; P < .001). The results were similar for BMD and for BMC. The patterns were similar in sensitivity analyses (eg, after excluding men with abdominal obesity, after excluding current smokers, after excluding men with ischemic heart disease or with diabetes mellitus, after excluding men with abnormal concentrations of lipids, bioavailable 17β-estradiol or 25-hydroxycholecalciferol, after excluding men with glomerular filtration rate <60 mL/min). CONCLUSION Severe AAC is associated with faster bone loss in older men and may contribute to the higher fracture risk observed in this population.
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Affiliation(s)
- Pawel Szulc
- INSERM UMR 1033, University of Lyon, Hospices Civils de Lyon, 69437, Lyon, France
| | - Joshua R Lewis
- Institute for Nutrition Research, Edith Cowan University, Joondalup, Perth, WA 6027, Australia
- Medical School, the University of Western Australia, Perth, WA 6009, Australia
| | - Roland Chapurlat
- INSERM UMR 1033, University of Lyon, Hospices Civils de Lyon, 69437, Lyon, France
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Yang N, Zhao Y, Bai Z, Chen H, Ning H, Zou M, Cheng G. The association of non-vitamin K antagonist oral anticoagulants vs. warfarin and the risk of fractures for patients with atrial fibrillation: a systematic review and meta-analysis. Acta Cardiol 2022; 78:298-310. [PMID: 36063197 DOI: 10.1080/00015385.2022.2030555] [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: 11/01/2022]
Abstract
BACKGROUND The fracture risks of non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin in patients with atrial fibrillation (AF) remain controversial. METHODS PubMed, Cochrane Library, EMBASE, Clinical Trials.gov databases for RCTs, and cohort studies were systematically searched from inception to 10 June 2021. RESULTS Twelve-two studies met the inclusion criteria and 477,821 patients were included. Warfarin increased the risk of fracture in AF patients compared with NOACs in overall any fracture (RR = 0.79; 95% CI = 0.70-10.88; p = 0.00), osteoporotic fracture (RR = 0.746; 95% CI = 0.630-0.883; p = 0.001). No significant difference was observed in the hip or pelvic fracture, vertebral fracture, extremity fracture, wrist fracture, femoral neck fracture, and ankle fracture. In subgroup analyses based on several aspects, NOACs were associated with a significant reduction in any fracture (standard dosage NOACs, cohort studies, elderly patients, rivaroxaban in RCTs, dabigatran, rivaroxaban, and apixaban in cohort studies), in the hip/pelvic fracture (follow-up time ≤1 year, cohort studies), and osteoporotic fracture (cohort studies). CONCLUSION NOACs were associated with a significantly lower risk of any fracture and osteoporotic fracture compared to warfarin. This benefit was also observed in specific NOACs types of dabigatran, rivaroxaban, and apixaban. However, whether NOACs had a less fracture risk than warfarin on the other risk of fractures was still uncertain.
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Affiliation(s)
- Nana Yang
- School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Ying Zhao
- School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Zhaohui Bai
- School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Haokun Chen
- School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Haoyu Ning
- School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Meijuan Zou
- Pharmaceutical College, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Gang Cheng
- Pharmaceutical College, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.,NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang, Liaoning, China
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Lu J, Hu D, Ma C, Shuai B. Advances in Our Understanding of the Mechanism of Action of Drugs (including Traditional Chinese Medicines) for the Intervention and Treatment of Osteoporosis. Front Pharmacol 2022; 13:938447. [PMID: 35774616 PMCID: PMC9237325 DOI: 10.3389/fphar.2022.938447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 05/23/2022] [Indexed: 12/12/2022] Open
Abstract
Osteoporosis (OP) is known as a silent disease in which the loss of bone mass and bone density does not cause obvious symptoms, resulting in insufficient treatment and preventive measures. The losses of bone mass and bone density become more severe over time and an only small percentage of patients are diagnosed when OP-related fractures occur. The high disability and mortality rates of OP-related fractures cause great psychological and physical damage and impose a heavy economic burden on individuals and society. Therefore, early intervention and treatment must be emphasized to achieve the overall goal of reducing the fracture risk. Anti-OP drugs are currently divided into three classes: antiresorptive agents, anabolic agents, and drugs with other mechanisms. In this review, research progress related to common anti-OP drugs in these three classes as well as targeted therapies is summarized to help researchers and clinicians understand their mechanisms of action and to promote pharmacological research and novel drug development.
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Tsai SHL, Hu CW, Shao SC, Tischler EH, Obisesan OH, Vervoort D, Chen WC, Hu JR, Kuo LT. Comparative Risks of Fracture Among Direct Oral Anticoagulants and Warfarin: A Systematic Review and Network Meta-Analysis. Front Cardiovasc Med 2022; 9:896952. [PMID: 35677694 PMCID: PMC9168033 DOI: 10.3389/fcvm.2022.896952] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/21/2022] [Indexed: 12/02/2022] Open
Abstract
Importance Previous studies have shown the effectiveness and safety of direct oral anticoagulants (DOACs), including lower fracture risks, compared to warfarin. However, direct or indirect comparisons between different DOACs are scarce in the literature. Objective This study aims to compare fracture risks among different DOACs and warfarin, including apixaban, rivaroxaban, dabigatran, and edoxaban, in patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Methods We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science for randomized controlled trials and cohort studies comparing the fracture risks among patients who used warfarin or DOACs, up to March 2021. Two authors extracted data and appraised the risk of bias of included studies. The primary outcome was fracture risk. We performed pairwise meta-analyses to compare differences between medications and network meta-analyses using frequentist random-effects models to compare through indirect evidence. We used surface under the cumulative ranking curve (SUCRA) and mean ranks to determine the probability of a DOAC ranking best in terms of fracture risk. Results Thirty-one studies were included in the final analysis. Twenty-four randomized controlled trials and seven cohort studies with 455,343 patients were included in the systematic review and network meta-analysis. Compared to warfarin, the risk of any fractures was lowest with apixaban [relative risk (RR) = 0.59; 95% confidence interval (CI): 0.48-0.73], followed by rivaroxaban (RR: 0.72; 95% CI: 0.60-0.86), edoxaban (RR: 0.88; 95% CI: 0.62-1.23), and dabigatran (RR = 0.90; 95% CI: 0.75-1.07). No substantial inconsistency between direct and indirect evidence was detected for all outcomes. Conclusions All DOACs were safer than warfarin concerning the risk of fracture; however, apixaban had the lowest relative risk of fracture within the class of DOACs. Further head-to-head prospective studies should confirm the comparative safety profiles of DOACs regarding fractures.
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Affiliation(s)
- Sung Huang Laurent Tsai
- Department of Orthopaedic Surgery, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ching-Wei Hu
- Department of Orthopaedic Surgery, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shih-Chieh Shao
- Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
| | - Eric H. Tischler
- Department of Orthopaedic Surgery and Rehabilitation Medicine, Downstate Medical Center, State University of New York, New York, NY, United States
| | - Olufunmilayo H. Obisesan
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
- Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Dominique Vervoort
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Wei Cheng Chen
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Jiun-Ruey Hu
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Liang-Tseng Kuo
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Sports Medicine, Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
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8
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Fawzy AM, Lip GYH. Warfarin and increased fracture risk? Answering the big question. Age Ageing 2022; 51:6530453. [PMID: 35191958 DOI: 10.1093/ageing/afab263] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Indexed: 11/12/2022] Open
Affiliation(s)
- Ameenathul M Fawzy
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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9
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The Effects of Osteoporotic and Non-osteoporotic Medications on Fracture Risk and Bone Mineral Density. Drugs 2021; 81:1831-1858. [PMID: 34724173 PMCID: PMC8578161 DOI: 10.1007/s40265-021-01625-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/11/2021] [Indexed: 12/26/2022]
Abstract
Osteoporosis is a highly prevalent bone disease affecting more than 37.5 million individuals in the European Union (EU) and the United States of America (USA). It is characterized by low bone mineral density (BMD), impaired bone quality, and loss of structural and biomechanical properties, resulting in reduced bone strength. An increase in morbidity and mortality is seen in patients with osteoporosis, caused by the approximately 3.5 million new osteoporotic fractures occurring every year in the EU. Currently, different medications are available for the treatment of osteoporosis, including anti-resorptive and osteoanabolic medications. Bisphosphonates, which belong to the anti-resorptive medications, are the standard treatment for osteoporosis based on their positive effects on bone, long-term experience, and low costs. However, not only medications used for the treatment of osteoporosis can affect bone: several other medications are suggested to have an effect on bone as well, especially on fracture risk and BMD. Knowledge about the positive and negative effects of different medications on both fracture risk and BMD is important, as it can contribute to an improvement in osteoporosis prevention and treatment in general, and, even more importantly, to the individual's health. In this review, we therefore discuss the effects of both osteoporotic and non-osteoporotic medications on fracture risk and BMD. In addition, we discuss the underlying mechanisms of action.
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Nagelkerke SCJ, Schoenmaker MHA, Tabbers MM, Benninga MA, van Ommen CH, Gouw SC. Prophylactic anticoagulation in children receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr 2021; 46:1036-1044. [PMID: 34719795 DOI: 10.1002/jpen.2298] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 10/13/2021] [Accepted: 10/25/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND Children with intestinal failure (IF) are at risk of loss of vascular access because of catheter-related venous thrombosis. Whether primary prophylactic anticoagulation is effective and safe in preventing catheter-related thrombosis is largely unknown. Our aim was to assess the incidences of catheter-related venous thrombosis and bleeding complications in children with IF receiving home parenteral nutrition (HPN) treated with primary prophylactic anticoagulation. METHODS All children, aged 0-18 years, treated with HPN at the Emma Children's Hospital/Amsterdam UMC were followed from January 2007 to July 2019. All patients were offered primary prophylactic anticoagulation from the start of HPN. The primary outcomes were catheter-related venous thrombosis and bleeding on prophylactic anticoagulation. RESULTS In total, 55 (76%) of 74 patients received primary prophylactic anticoagulation. The median age at the start of prophylaxis was 8.4 (interquartile range [IQR], 5.0-55.7) months. Patients were followed for a median of 31.2 (IQR, 10.7-53.5) months, with a total of 65,463 catheter days. The incidence of catheter-related thrombosis on prophylactic anticoagulation was 0.2 per 1000 catheter days. In total, the incidence of clinically relevant bleeding was 0.1 per 1000 catheter days. The median time to first event was 1268 (IQR, 149-2014) days for thrombosis and 389 (IQR, 227-2912) days for clinically relevant bleeding. Cumulative event-free survival after 5 years was 78% for thrombosis. CONCLUSIONS Our study shows a low rate of catheter-related venous thrombosis and a slightly elevated rate of clinically relevant bleeding in children receiving HPN and primary prophylactic anticoagulation.
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Affiliation(s)
- Sjoerd Cornelis Johannes Nagelkerke
- Pediatric Gastroenterology, Hepatology, and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.,Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.,Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, the Netherlands
| | | | - Merit M Tabbers
- Pediatric Gastroenterology, Hepatology, and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.,Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.,Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, the Netherlands
| | - Marc Alexander Benninga
- Pediatric Gastroenterology, Hepatology, and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.,Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.,Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, the Netherlands
| | - C Heleen van Ommen
- Pediatric Hematology, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Samantha C Gouw
- Pediatric Hematology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.,Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.,Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
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11
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He N, Dell'Aniello S, Zhai S, Suissa S, Renoux C. Risk of fracture in patients with non-valvular atrial fibrillation initiating direct oral anticoagulants vs. vitamin K antagonists. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2021; 7:389-397. [PMID: 32722764 PMCID: PMC8453296 DOI: 10.1093/ehjcvp/pvaa094] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/16/2020] [Accepted: 07/21/2020] [Indexed: 12/27/2022]
Abstract
AIMS To determine the risk of fracture associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF), accounting for cumulative duration of use. METHODS AND RESULTS Using Quebec administrative healthcare databases, we formed a cohort of all patients aged 40 years or older newly diagnosed with NVAF, who filled a first prescription for DOACs or VKAs between 2011 and 2014. Exposure was modelled as a time-varying variable whereby patients were considered unexposed up to 180 days of cumulative duration of use (to account for a biologically meaningful exposure) and exposed thereafter. The final cohort included 10 306 new users of DOACs and 15 357 new users of VKAs. After propensity score-based fine stratification and weighting, use of DOACs for 180 days or greater was associated with a 35% decreased risk of fracture [crude incidence rates 7.5 vs. 15.3 per 1000 person-years; adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.46-0.91] compared to VKA duration ≥180 days. Direct oral anticoagulants use was also associated with a lower risk of hip fracture (HR 0.51, 95% CI 0.31-0.86) compared with VKAs. There was no difference in the rate of fracture for shorter duration of use (HR 1.10; 95% CI 0.79-1.53). The risk was not modified by age, sex, chronic kidney disease, osteoporosis, history of fracture or falls. CONCLUSION Prolonged use of DOACs is associated with a lower risk of fracture compared with VKAs. These findings support the first-line recommendation for DOACs in patients with NVAF.
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Affiliation(s)
- Na He
- Department of Pharmacy, Peking University Third Hospital, 49 Huayuan North Road, Beijing 100191, China
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, Montreal, Québec H3T 1E2, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal, Québec H3A 1A2, Canada
| | - Sophie Dell'Aniello
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, Montreal, Québec H3T 1E2, Canada
| | - Suodi Zhai
- Department of Pharmacy, Peking University Third Hospital, 49 Huayuan North Road, Beijing 100191, China
| | - Samy Suissa
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, Montreal, Québec H3T 1E2, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal, Québec H3A 1A2, Canada
| | - Christel Renoux
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, Montreal, Québec H3T 1E2, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal, Québec H3A 1A2, Canada
- Department of Neurology and Neurosurgery, McGill University, 853 Sherbrooke Street West, Montreal, Québec H3A 0G5, Canada
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Khanra D, Mukherjee A, Deshpande S, Khan H, Kathuria S, Kella D, Padmanabhan D. A Network Meta-Analysis Comparing Osteoporotic Fracture among Different Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation. J Bone Metab 2021; 28:139-150. [PMID: 34130366 PMCID: PMC8206613 DOI: 10.11005/jbm.2021.28.2.139] [Citation(s) in RCA: 2] [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: 01/31/2001] [Accepted: 04/19/2021] [Indexed: 12/14/2022] Open
Abstract
Background There are limited studies comparing the risk of osteoporosis and fractures between different direct oral anticoagulants (DOACs) and vitamin K antagonists (VKA) in non-valvular atrial fibrillation (AF). Using a network meta-analysis (NMA), we compared osteoporotic fractures among 5 different treatment arms, viz. dabigatran, rivaroxaban, apixaban, edoxaban, and VKA. Methods Ten studies, including 5 randomized control trials and 5 population-based studies, with a total of 321,844 patients (148,751 and 173,093 in the VKA and DOAC group, respectively) with a median follow-up of 2 years, were included. A Bayesian random-effects NMA model comparing fractures among the treatment arms was performed using MetInsight V3. Sensitivity analysis excluded studies with the highest residual deviances from the NMA model. Results The mean age of the patients was 70 years. The meta-analysis favored DOACs over VKA with significantly lower osteoporotic fracture (odds ratio [OR], 0.77; 95% credible interval [CrI], 0.70–0.86). The NMA demonstrated that fractures were significantly lower with apixaban compared with dabigatran (OR, 0.64; 95% CrI, 0.44–0.95); however, fractures were statistically similar between apixaban and rivaroxaban (OR, 0.84; 95% CrI, 0.58–1.24) and dabigatran and rivaroxaban (OR, 1.32; 95% CrI, 0.90–1.87). Based on the Bayesian model of NMA, the probability of osteoporotic fracture was highest with VKA and lowest with apixaban, followed by rivaroxaban, edoxaban, and dabigatran. Conclusions The decision to prescribe anticoagulants in elderly patients with AF should be made not only based on thrombotic and bleeding risks but also on the risk of osteoporotic fracture; these factors should be considered and incorporated in contemporary cardiology practice.
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Affiliation(s)
- Dibbendhu Khanra
- Heart and Lung Center, New Cross Hospital, Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom
| | | | - Saurabh Deshpande
- Department of Cardiology, Sri Jayadeva Institute of Cardiac Sciences and Research, Bengaluru, India
| | - Hassan Khan
- Center for the Prevention of Cardiovascular Disease, The Leon H. Charney Division of Cardiology, NYU Langone Health, NYU Robert I. Grossman School of Medicine, New York, USA
| | | | | | - Deepak Padmanabhan
- Department of Cardiology, Sri Jayadeva Institute of Cardiac Sciences and Research, Bengaluru, India
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Kuo LT, Lin SJ, Wu VCC, Chang JJ, Chu PH, Lin YS. Direct oral anticoagulants and the risk of osteoporotic fractures in patients with non-valvular atrial fibrillation. Ther Adv Musculoskelet Dis 2021; 13:1759720X211011374. [PMID: 33995605 PMCID: PMC8083002 DOI: 10.1177/1759720x211011374] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 03/30/2021] [Indexed: 11/17/2022] Open
Abstract
Background: The incidence of osteoporotic fracture increases with age, particularly in elderly populations with atrial fibrillation (AF). However, direct oral anticoagulants (DOACs) have less effect on osteoporotic fracture than vitamin K antagonists, it is unclear whether the risk of osteoporotic fracture is affected by different types and doses of DOACs in AF patients. Methods: This nationwide population-based cohort study included AF patients prescribed DOACs between 2011 and 2016 taken from the Taiwan National Health Insurance database. Adjusted hazard ratios (aHRs) for the risk of osteoporotic, hip, and spine fractures between DOAC users were compared using the Fine and Gray subdistribution hazard model to adjust for possible confounders. Results: A total of 56,795 patients who were prescribed DOACs were included in the present study. Among them, 24,597 patients received dabigatran, 26,968 received rivaroxaban, and 5230 received apixaban. After 2 years’ follow up, there was no significant difference in the incidence of osteoporotic, spine, or hip fracture among those receiving dabigatran, rivaroxaban, or apixaban. Subgroup analysis showed that patients taking dabigatran had a higher incidence of osteoporotic and hip fracture than those taking rivaroxaban and apixaban in cases with concomitant peripheral artery disease (PAD) or a history of hip fracture (p for interaction: 0.004 and 0.030, respectively). However, dabigatran users had a lower incidence of osteoporotic fracture and spine fracture in those receiving standard-dose DOACs compared with rivaroxaban and apixaban; whereas, they had a higher incidence of hip fractures when administered at low dose. Conclusion: AF patients with different DOACs did not have different risks of osteoporotic fracture overall. However, additional concomitant morbidities, such as PAD or a history of hip fracture, and standard/low doses might be associated with different risks for different DOACs. These findings should be taken into consideration in the clinic when the DOAC is being chosen. Plain language summary Different direct oral anticoagulants had different impact on osteoporotic fracture Anticoagulation therapy is an essential therapy in atrial fibrillation (AF) patients, but osteoporotic fracture is another important issue in these patients prescribed with anticoagulants. However, no study has been conducted to evaluate the impact of different DOACs on different types of osteoporotic fractures. In our findings, although different DOACs had no significantly different impact on osteoporotic fractures, dabigatran users had a slightly higher incidence of osteoporotic and hip fractures among different DOACs, particularly in those have simultaneously had peripheral artery disease, a history of hip fracture. In addition, when AF patients taking low-dose DOACs, dabigatran users also have higher incidence of hip fracture than those taking other DOACs.
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Affiliation(s)
- Liang-Tseng Kuo
- Division of Sports Medicine, Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Su-Ju Lin
- Division of Nephrology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Victor Chien-Chia Wu
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Jung-Jung Chang
- Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Pao-Hsien Chu
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Yu-Sheng Lin
- Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, No. 6 West Sec., Chia-Pu Road, Putz City, Chiayi 61363
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Jørgensen HS, David K, Salam S, Evenepoel P. Traditional and Non-traditional Risk Factors for Osteoporosis in CKD. Calcif Tissue Int 2021; 108:496-511. [PMID: 33586002 DOI: 10.1007/s00223-020-00786-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 12/02/2020] [Indexed: 12/11/2022]
Abstract
Osteoporosis is a state of bone fragility with reduced skeletal resistance to trauma, and consequently increased risk of fracture. A wide range of conditions, including traditional risk factors, lifestyle choices, diseases and their treatments may contribute to bone fragility. It is therefore not surprising that the multi-morbid patient with chronic kidney disease (CKD) is at a particularly high risk. CKD is associated with reduced bone quantity, as well as impaired bone quality. Bone fragility in CKD is a composite of primary osteoporosis, accumulation of traditional and uremia-related risk factors, assaults brought on by systemic disease, and detrimental effects of drugs. Some risk factors are modifiable and represent potential targets for intervention. This review provides an overview of the heterogeneity of bone fragility in CKD.
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Affiliation(s)
- Hanne Skou Jørgensen
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Karel David
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Syazrah Salam
- Sheffield Kidney Institute, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, UK
- Academic Unit of Bone Metabolism and 3 Mellanby Centre for Bone Research, Medical School, University of Sheffield, Sheffield, UK
| | - Pieter Evenepoel
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
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15
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Cassidy L, Hill L, Fitzsimons D, McGaughey J. The impact of psychoeducational interventions on the outcomes of caregivers of patients with heart failure: A systematic review and meta-analysis. Int J Nurs Stud 2021; 114:103806. [PMID: 33248290 DOI: 10.1016/j.ijnurstu.2020.103806] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 10/15/2020] [Accepted: 10/16/2020] [Indexed: 01/15/2023]
Abstract
BACKGROUND Heart failure is a global health care problem that causes a significant economic burden. Despite medical advancements, it's prognosis remains poor as many patients with heart failure experience symptoms that negatively impact Quality of Life. Caregivers are often responsible for helping and supporting family members manage their heart failure symptoms at home. In addition to managing their own medical problems and maintaining social and personal lives, significant burden and stress can occur. At present, caregivers receive little guidance or information to support them in their caregiving role. OBJECTIVES This review aims to determine the impact of psychoeducational interventions on the outcomes of caregivers of patients with heart failure. DESIGN Systematic review and meta-analysis. DATA SOURCE Five electronic databases: PsycINFO, Medline, CINAHL Plus, EMBASE and SCOPUS were searched from June 2007 to August 2019. REVIEW METHODS The conduct and reporting of this review was based on the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Cochrane Risk of Bias Tool was used to assess the risk of bias amongst randomised controlled trials, and the Newcastle Ottawa Scale was used to assess risk of bias in one quasi-experimental study. RESULTS Ten articles met the inclusion criteria, consisting of seven studies, with a total sample size of 953 participants. The pooled result from two studies, conducted in America and China, reported that psychoeducational interventions significantly reduced depression at six months' follow-up (SMD -0.82; 95% CI -1.17 to -0.47; p = 0.73, I2 =0%). The pooled result from two studies conducted in Sweden and Taiwan showed a significant improvement in heart failure knowledge at six months' follow-up (SMD 0.97; 95% CI 0.70 to 1,25; p < 0.00001, I2 =0%). Finally, pooled results from three studies conducted in Sweden, China and Taiwan found a significant improvement in Quality of Life at 3 months' follow- up (SMD 0.25; 95% CI 0.25 to 0.48; p = 0.03). The three most common intervention components included: group based educational sessions, telemonitoring and telephone support, and written resources. CONCLUSIONS There was no specific type of psychoeducational intervention found to have a significant impact on caregiver outcomes, as interventions were heterogeneous consisting of multiple components. Further research is needed to determine the effectiveness of individual and combined components to identify the ideal intervention format and design for caregivers of patients with heart failure.
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Affiliation(s)
- Lorna Cassidy
- Queen's University Belfast, School of Nursing and Midwifery, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland.
| | - Loreena Hill
- Queen's University Belfast, School of Nursing and Midwifery, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland.
| | - Donna Fitzsimons
- Queen's University Belfast, School of Nursing and Midwifery, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland; All-Ireland Institute for Hospice And Palliative Care, Our Lady's Hospice and Care Services, Harold's Cross Rd, Harold's Cross, Dublin, Ireland.
| | - Jennifer McGaughey
- Queen's University Belfast, School of Nursing and Midwifery, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland.
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16
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Chen J, Lyu L, Shen J, Zeng C, Chen C, Wei T. The association of fracture risk in atrial fibrillation patients and long-term anticoagulant therapy category: a systematic review and meta-analysis. PeerJ 2021; 9:e10683. [PMID: 33552723 PMCID: PMC7842143 DOI: 10.7717/peerj.10683] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 12/09/2020] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Our study aimed to assess the risk of all fractures and hip fractures in patients with atrial fibrillation (AF) who took non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin. METHODS We searched PubMed, Embase, and Cochrane Library and Clinical Trials.gov Website. Reviewed related researches up to January 31, 2020, to identify studies with more than 12 months of follow-up data. The protocol for this systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42020156893). RESULTS We included five RCT studies, and five observational studies that contained a total of 326,846 patients in our meta-analysis. Our meta-analysis showed that patients taken NOACs had no significant all fracture risk (RR = 0.91, 95% CI [0.81-1.01]) and hip fracture risk (RR = 0.92, 95% CI [0.82-1.03]) compared with those taken warfarin. Subanalysis showed that the risk of all fractures and hip fractures treated by NOACs were significant lower compared with warfarin in observational studies compared with RCT studies. Also, a subanalysis across the duration of anticoagulation showed the NOACs users have lower all fracture risk than warfarin users when the duration of anticoagulation ≤2 years (RR = 0.89, 95% CI [0.80-0.99]). Further analysis, significant lower all fracture risk in the rivaroxaban therapy (RR = 0.81; 95% CI [0.76-0.86]) compared with warfarin but no statistical significance in hip fracture. There were no significant difference of all fracture risk and hip fracture risk in dabigatran, apixaban, and edoxaban therapy compared with warfarin. CONCLUSION The meta-analysis demonstrated that NOACs associated with a significantly lower all fracture risk compared with warfarin when the duration of anticoagulation more than 2 years. Rivaroxaban users had lower risk of all fracture than warfarin users in AF patients. But there was no evidence to verify apixaban, edoxaban, and dabigatranin could decrease all fracture and hip fracture risk compared with warfarin.
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Affiliation(s)
- Jun Chen
- Medical College of Zhejiang University, Hangzhou, Zhejiang, China
| | - Lingchun Lyu
- Lishui Hospital of Zhejiang University School of Medicine, Lishui, Zhejiang, China
| | - Jiayi Shen
- Lishui Hospital of Zhejiang University School of Medicine, Lishui, Zhejiang, China
| | - Chunlai Zeng
- Lishui Hospital of Zhejiang University School of Medicine, Lishui, Zhejiang, China
| | - Cheng Chen
- Lishui Hospital of Zhejiang University School of Medicine, Lishui, Zhejiang, China
| | - Tiemin Wei
- Lishui Hospital of Zhejiang University School of Medicine, Lishui, Zhejiang, China
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De Caterina R, Mundi S, Fusaro M. Vitamin K antagonists and osteoporotic fractures: insights from comparisons with the NOACs. Eur Heart J 2021; 41:1109-1111. [PMID: 32083296 DOI: 10.1093/eurheartj/ehaa077] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Abstract
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Affiliation(s)
- Raffaele De Caterina
- Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa; and Fondazione VillaSerena per la Ricerca, Città Sant'Angelo, Pescara, Italy
| | - Santa Mundi
- National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy and Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali (DiSTeBA), University of Salento, Lecce, Italy
| | - Maria Fusaro
- CNR Institute of Clinical Physiology (IFC), Pisa, Italy and Dipartimento di Medicina, University of Padova, Italy
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18
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Collin C, Bimou C, Mabit C, Tchalla A, Charissoux JL, Marcheix PS. Orthogeriatric assessment of patients over 75 years of age with a proximal femur fracture: Predictors of 6-month mortality. Orthop Traumatol Surg Res 2020; 106:1441-1447. [PMID: 33060014 DOI: 10.1016/j.otsr.2020.06.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 05/29/2020] [Accepted: 06/01/2020] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Proximal femur fractures are common and dangerous in older adults, given the high short-term mortality rate. While surgical treatment is vital, medical orthogeriatric care may reduce the 6-month mortality rate; however, this has not been determined on a broad scale in France. This led us to conduct a retrospective study to answer the following questions: (1) Does delayed surgical treatment impact the 6-month mortality rate? (2) Are there correctable medical factors that impact the 6-month mortality? HYPOTHESIS Delayed surgical treatment is not an isolated risk factor for higher 6-month mortality after proximal femur fracture. METHODS We included all patients 75 years or older who had suffered a proximal femur fracture requiring surgical treatment. This allowed us to analyze the medical records of 476 patients retrospectively. We documented their comorbidities and pre-, intra- and postoperative characteristics. A univariate then multivariate analysis was done to identify risk factors for mortality at 6 months. RESULTS In the univariate analysis, time to surgery of more than 48hours increased the risk of dying at 6 months by 1.5 fold (Odds ratio (OR)=1.57/95% CI: 1-2.48/p=0.04). However, this risk factor was not significant in the multivariate analysis since it is not an independent risk factor. In the multivariate analysis, anticoagulants (OR=2/95% CI: 1.13-3.50/p=0.02), dementia (OR=2.2/95% CI: 1.32-3.59/p=0.002), peripheral artery disease (OR=2.9/95% CI: 1.10-7.70/p=0.03), 2-point drop in hemoglobin count from preoperative to postoperative (OR=1.9/95% CI: 1.05-3.12/p=0.04), male sex (OR=1.82/95% CI: 1.05-3.12/p=0.04), age above 85 years (OR=5.26/95% CI: 1.49-5.26/p=0.002) and Charlson comorbidity index≥7 (OR=2.13/95% CI: 1.29-3.52/p=0.003) were statistically associated with mortality at 6 months. DISCUSSION/CONCLUSION Our study found that the patients most at risk for dying within 6 months of a hip fracture were males, older than 85 and have associated medical conditions (Charlson index≥7). Prior anticoagulant treatment increases the time to surgery in our study and therefore increases the risk of these patients dying within 6 months. Treatment of these at-risk patients should ensure that their underlying medical conditions are not made worse, while providing treatment within 48hours. Patients taking anticoagulants must be monitored carefully to ensure surgical treatment is not delayed. LEVEL OF EVIDENCE IV, retrospective study without control group.
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Affiliation(s)
- Camille Collin
- Service d'orthopédie-traumatologie, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France
| | - Charlotte Bimou
- EA 6310 HAVAE handicap activité vieillissement autonomie environnement, université de Limoges, 33, rue François-Mitterrand, 87032 Limoges, France
| | - Christian Mabit
- Service d'orthopédie-traumatologie, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France
| | - Achille Tchalla
- Service de médecine gériatrique, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France
| | - Jean-Louis Charissoux
- Service d'orthopédie-traumatologie, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France
| | - Pierre-Sylvain Marcheix
- Service d'orthopédie-traumatologie, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France.
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Marietta M, Coluccio V, Boriani G, Luppi M. Effects of Anti-vitamin k oral anticoagulants on bone and cardiovascular health. Eur J Intern Med 2020; 79:1-11. [PMID: 32553585 DOI: 10.1016/j.ejim.2020.05.032] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 05/01/2020] [Accepted: 05/21/2020] [Indexed: 12/16/2022]
Abstract
Vitamin K antagonist oral anticoagulants (VKAs) have been proven over 50 years to be highly effective and acceptably safe in many settings and are still used by millions of people worldwide. The main concern about the safety of VKAs regards the risk of bleeding, but there is accumulation evidence of their potentially negative effects beyond hemostasis. Indeed, VKAs impair the action of several Vitamin-K Dependent Proteins (VKDP), such as Bone Gla protein, Matrix Gla protein, Gas6 Protein, Periostin and Gla-Ric Protein, involved in bone and vascular metabolism, thus exerting a detrimental effect on bone and vascular health. Indeed, although the evidence regarding this issue is not compelling, it has been shown that VKAs use decreases bone mass density, increases the risk of bone fractures and accelerates the process of vascular and valvular calcification. Vascular calcification is a major concern in Chronic Kidney Disease (CKD) patients, also in absence of VKAs, because of mineral metabolism derangement, chronic inflammation and oxidative stress. Direct Oral AntiCoagulants (DOACs) do not affect VKDP involved in vascular and valvular calcification, and do not induce calcific valve degeneration in animal models, being a possible alternative to AVK for CKD patients. However, the efficacy and safety of DOACs in this population, suggested by some recent observations, requires confirmation by dedicated, randomized study. We reviewed here the effects of VKAs in bone and vascular health as compared to DOACs, in order to provide the physicians with some data useful to wisely choose the most suitable anticoagulant for every patient.
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Affiliation(s)
- Marco Marietta
- Hematology Unit, Azienda Ospedaliero-Universitaria, Modena, Italy.
| | - Valeria Coluccio
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy
| | - Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy
| | - Mario Luppi
- Hematology Unit, Azienda Ospedaliero-Universitaria, Modena, Italy; Department of Medical and Surgical Sciences, Section of Hematology, University of Modena and Reggio Emilia, Modena, Italy
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Muñoz-Garach A, García-Fontana B, Muñoz-Torres M. Nutrients and Dietary Patterns Related to Osteoporosis. Nutrients 2020; 12:nu12071986. [PMID: 32635394 PMCID: PMC7400143 DOI: 10.3390/nu12071986] [Citation(s) in RCA: 150] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/26/2020] [Accepted: 07/01/2020] [Indexed: 02/07/2023] Open
Abstract
Osteoporosis is a common chronic disease characterized by a decrease in bone mineral density, impaired bone strength, and an increased risk of fragility fractures. Fragility fractures are associated with significant morbidity, mortality and disability and are a major public health problem worldwide. The influence of nutritional factors on the development and progression of this disease can be significant and is not yet well established. Calcium intake and vitamin D status are considered to be essential for bone metabolism homeostasis. However, some recent studies have questioned the usefulness of calcium and vitamin D supplements in decreasing the risk of fractures. The adequate intake of protein, vegetables and other nutrients is also of interest, and recommendations have been established by expert consensus and clinical practice guidelines. It is important to understand the influence of nutrients not only in isolation but also in the context of a dietary pattern, which is a complex mixture of nutrients. In this review, we evaluate the available scientific evidence for the effects of the main dietary patterns on bone health. Although some dietary patterns seem to have beneficial effects, more studies are needed to fully elucidate the true influence of diet on bone fragility.
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Affiliation(s)
- Araceli Muñoz-Garach
- Department of Endocrinology and Nutrition, Virgen de las Nieves Hospital, 18014 Granada, Spain
- Correspondence: (A.M.-G.); (M.M.-T.)
| | - Beatriz García-Fontana
- Instituto de Investigación Biosanitaria (Ibs.GRANADA), 18014 Granada, Spain;
- CIBERFES, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Manuel Muñoz-Torres
- Instituto de Investigación Biosanitaria (Ibs.GRANADA), 18014 Granada, Spain;
- CIBERFES, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Unidad de Gestión Clínica Endocrinología y Nutrición, Hospital Universitario San Cecilio de Granada, 18016 Granada, Spain
- Department of Medicine, University of Granada, 18016 Granada, Spain
- Correspondence: (A.M.-G.); (M.M.-T.)
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Lutsey PL, Norby FL, Ensrud KE, MacLehose RF, Diem SJ, Chen LY, Alonso A. Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation. JAMA Intern Med 2020; 180:245-253. [PMID: 31764956 PMCID: PMC6902159 DOI: 10.1001/jamainternmed.2019.5679] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
IMPORTANCE Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk. OBJECTIVE To test the hypothesis that, among patients with nonvalvular AF, use of DOACs vs warfarin is associated with lower risk of incident fracture. DESIGN, SETTING, AND PARTICIPANTS This comparative effectiveness cohort study used the MarketScan administrative claims databases to identify patients with nonvalvular AF and who were prescribed oral anticoagulants from January 1, 2010, through September 30, 2015. To reduce confounding, patients were matched on age, sex, CHA2DS2-VASc (congestive heart failure, hypertension, age [>65 years = 1 point; >75 years = 2 points], diabetes, and previous stroke/transient ischemic attack [2 points], vascular disease) score, and high-dimensional propensity scores. The final analysis included 167 275 patients with AF. Data were analyzed from February 27, 2019 to September 18, 2019. EXPOSURES Warfarin and DOACs (dabigatran etexilate, rivaroxaban, and apixaban). MAIN OUTCOMES AND MEASURES Incident hip fracture, fracture requiring hospitalization, and all clinical fractures (identified using inpatient or outpatient claims) defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS In the study population of 167 275 patients with AF (38.0% women and 62.0% men; mean [SD] age, 68.9 [12.5] years), a total of 817 hip fractures, 2013 hospitalized fractures, and 7294 total fractures occurred during a mean (SD) follow-up of 16.9 (13.7) months. In multivariable-adjusted, propensity score-matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88-0.98), whereas the association with hip fractures (HR, 0.91; 95% CI, 0.78-1.07) was not statistically significant. When comparing individual DOACs with warfarin, the strongest findings were for apixaban (HR for hip fracture, 0.67 [95% CI, 0.45-0.98]; HR for fractures requiring hospitalization, 0.60 [95% CI, 0.47-0.78]; and HR for all clinical fractures, 0.86 [95% CI, 0.75-0.98]). In subgroup analyses, DOACs appeared more beneficial among patients with AF who also had a diagnosis of osteoporosis than among those without a diagnosis of osteoporosis. CONCLUSIONS AND RELEVANCE In this real-world population of 167 275 patients with AF, use of DOACs-particularly apixaban-compared with warfarin use was associated with lower fracture risk. These associations were more pronounced among patients with a diagnosis of osteoporosis. Given the potential adverse effects of warfarin on bone health, these findings suggest that caution should be used when prescribing warfarin to patients with AF at high risk of fracture.
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Affiliation(s)
- Pamela L Lutsey
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis
| | - Faye L Norby
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis
| | - Kristine E Ensrud
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis.,Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota.,Department of Medicine, University of Minnesota School of Medicine, Minneapolis
| | - Richard F MacLehose
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis
| | - Susan J Diem
- Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota.,Department of Medicine, University of Minnesota School of Medicine, Minneapolis
| | - Lin Y Chen
- Department of Medicine, University of Minnesota School of Medicine, Minneapolis
| | - Alvaro Alonso
- Rollins School of Public Health, Department of Epidemiology, Emory University, Atlanta, Georgia
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Yokoyama S, Ieda S, Nagano M, Nakagawa C, Iwase M, Hosomi K, Takada M. Association between oral anticoagulants and osteoporosis: Real-world data mining using a multi-methodological approach. Int J Med Sci 2020; 17:471-479. [PMID: 32174777 PMCID: PMC7053309 DOI: 10.7150/ijms.39523] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 01/08/2020] [Indexed: 01/10/2023] Open
Abstract
Introduction: Warfarin and direct oral anticoagulants (DOACs) have been widely used in antithrombotic therapy. Although warfarin use has been suspected to be associated with osteoporosis risk, several studies have shown otherwise. Conversely, a few reports have found an association between DOACs and osteoporosis. This study therefore clarifies the association between oral anticoagulants and osteoporosis by analyzing real-world data using different methodologies, algorithms, and databases. Methods: Real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS; 2004-2016) and Japanese administrative claims database (2005-2017; JMDC Inc., Tokyo) were used. Reporting odds ratio (ROR) and information component (IC) were calculated through disproportionality analysis (DPA) using reports recorded in the FAERS. Sequence symmetry analysis (SSA) was employed to calculate the adjusted sequence ratio (SR) using the JMDC Claims Database. For the adjusted SR and ROR, a significant signal was detected when the lower limit of the two-sided 95% confidence interval (CI) was more than 1. For the IC, a significant signal was detected when the lower limit of the 95% CI was more than 0. Results: DPA for warfarin found significant signals for osteoporosis in ROR (1.43, 95% CI: 1.32-1.54) and IC (0.50, 95% CI: 0.39-0.61). SSA showed a significant association between warfarin use and osteoporosis or bisphosphonate use. Moreover, a significant association was observed in males and females, albeit only for warfarin. Conclusion: Multi-methodological data mining revealed that warfarin use, not DOACs, is significantly associated with osteoporosis regardless of sex difference.
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Affiliation(s)
- Satoshi Yokoyama
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
| | - Shoko Ieda
- Department of Pharmacy, Kindai University Hospital, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Mirai Nagano
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
| | - Chihiro Nakagawa
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
| | - Makoto Iwase
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
| | - Kouichi Hosomi
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
| | - Mitsutaka Takada
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
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24
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Mott A, Bradley T, Wright K, Cockayne ES, Shearer MJ, Adamson J, Lanham-New SA, Torgerson DJ. Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporos Int 2019; 30:1543-1559. [PMID: 31076817 DOI: 10.1007/s00198-019-04949-0] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 03/19/2019] [Indexed: 11/24/2022]
Abstract
UNLABELLED Vitamin K may affect bone mineral density and fracture incidence. Since publication of a previous systematic review the integrity of some of the previous evidence has been questioned and further trials have been published. Therefore an update to the systematic review was required. INTRODUCTION This systematic review was designed to assess the effectiveness of oral vitamin K supplementation for increasing bone mineral density and reducing fractures in adults. METHODS MEDLINE, EMBASE, CENTRAL, CINAHL, clinicaltrials.gov, and WHO-ICTRP were searched for eligible trials. Randomised controlled trials assessing oral vitamin K supplementation that assessed bone mineral density or fractures in adult populations were included. A total of 36 studies were identified. Two independent reviewers extracted data using a piloted extraction form. RESULTS For post-menopausal or osteoporotic patients, meta-analysis showed that the odds of any clinical fracture were lower for vitamin K compared to controls (OR, 0.72, 95%CI 0.55 to 0.95). Restricting the analysis to low risk of bias trials reduced the OR to 0.76 (95%CI, 0.58 to 1.01). There was no difference in vertebral fractures between the groups (OR 0.96, 95%CI 0.83 to 1.11). In the bone mineral density meta-analysis, percentage change from baseline at the lumbar spine was higher at 1 year (MD 0.93, 95%, CI - 0.02 to 1.89) and 2 years (MD 1.63%, 95%CI 0.10 to 3.16) for vitamin K compared to controls; however, removing trials at high risk of bias tended to result in smaller differences that were not statistically significant. At 6 months, it was higher in the hip (MD 0.42%, 95%CI 0.01 to 0.83) and femur (MD 0.29%, 95%CI 0.17 to 0.42). There was no significant difference at other anatomical sites. CONCLUSIONS For post-menopausal or osteoporotic patients, there is no evidence that vitamin K affects bone mineral density or vertebral fractures; it may reduce clinical fractures; however, the evidence is insufficient to confirm this. There are too few trials to draw conclusions for other patient groups.
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Affiliation(s)
- A Mott
- York Trials Unit, Department of Health Sciences, University of York, ARRC Building, York, YO10 5DD, UK.
| | - T Bradley
- Chesterfield Hospital, Chesterfield Road, Calow, S44 5BL, UK
| | - K Wright
- Centre for Reviews & Dissemination, University of York, York, YO10 5DD, UK
| | - E S Cockayne
- York Trials Unit, Department of Health Sciences, University of York, ARRC Building, York, YO10 5DD, UK
| | - M J Shearer
- Centre for Haemostasis and Thrombosis, Guy's and St Thomas' NHS Trust, London, SE1 7EH, UK
| | - J Adamson
- Institute of Health & Society, Newcastle University, Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK
| | - S A Lanham-New
- Nutritional Sciences Department, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK
| | - D J Torgerson
- York Trials Unit, Department of Health Sciences, University of York, ARRC Building, York, YO10 5DD, UK
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25
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Evenepoel P, Claes K, Meijers B, Laurent M, Bammens B, Naesens M, Sprangers B, Pottel H, Cavalier E, Kuypers D. Poor Vitamin K Status Is Associated With Low Bone Mineral Density and Increased Fracture Risk in End-Stage Renal Disease. J Bone Miner Res 2019; 34:262-269. [PMID: 30427544 DOI: 10.1002/jbmr.3608] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 09/04/2018] [Accepted: 10/06/2018] [Indexed: 01/04/2023]
Abstract
Chronic kidney disease and osteoporosis are major public health problems associated with an aging population. Vitamin K insufficiency is prevalent among patients with end-stage renal disease (ESRD). Preliminary data indicate that poor vitamin K status may compromise bone health and that increased inflammation may be in the causal pathway. We performed an ancillary analysis of data collected in the frame of prospective observational cohort studies exploring various aspects of bone health in de novo renal transplant recipients to investigate the association between vitamin K status, inflammation, bone mineral density, and incident clinical fractures. Parameters of mineral metabolism (including biointact PTH and FGF23, sclerostin, calcidiol, calcitriol) and inflammation (CRP and IL-6), osteoprotegerin, bone turnover markers (P1NP, BsAP, and TRAP5B), and dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP) were assessed on blood samples collected immediately prior to kidney transplantation in 468 patients. Areal bone mineral density (aBMD) was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry within 14 days posttransplant. Poor vitamin K status, defined by dp-ucMGP >500 nmol/L, was highly prevalent (90%). High dp-ucMGP levels independently associated with elevated inflammatory markers and low aBMD. No associations were observed between vitamin K status and bone turnover markers. During a median follow-up of 5.1 years, 33 patients sustained a fragility fracture. In Cox-proportional hazards analysis, a dp-ucMGP above median associated with incident fractures, independent of classical determinants, including age, gender, history of fracture, and aBMD (HR 2.21; 95% CI, 1.00 to 4.91; p < 0.05). In conclusion, poor vitamin K status associates with inflammation and low aBMD in patients with ESRD and confers an increased risk of incident fractures in de novo renal transplant recipients. © 2018 American Society for Bone and Mineral Research.
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Affiliation(s)
- Pieter Evenepoel
- Laboratory of Nephrology, Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Kathleen Claes
- Laboratory of Nephrology, Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Bjorn Meijers
- Laboratory of Nephrology, Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Michaël Laurent
- Centre for Metabolic Bone Diseases, KU Leuven, Leuven, Belgium
| | - Bert Bammens
- Laboratory of Nephrology, Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Maarten Naesens
- Laboratory of Nephrology, Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Ben Sprangers
- Laboratory of Nephrology, Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Hans Pottel
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
| | | | - Dirk Kuypers
- Laboratory of Nephrology, Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
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26
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Fiordellisi W, White K, Schweizer M. A Systematic Review and Meta-analysis of the Association Between Vitamin K Antagonist Use and Fracture. J Gen Intern Med 2019; 34:304-311. [PMID: 30511289 PMCID: PMC6374254 DOI: 10.1007/s11606-018-4758-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 10/04/2018] [Accepted: 11/16/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND Vitamin K antagonist (VKA) anticoagulant use is suspected to increase the risk of bone fracture through inhibition of vitamin K-dependent cofactors of bone formation, an effect not seen with non-vitamin K antagonist oral anticoagulants (NOACs). The purpose of our systematic review and meta-analysis is to investigate the association between VKA use and fracture. METHODS We searched PubMed, EMBASE, and Cochrane Library for studies analyzing fracture in adults using VKAs versus controls. Two authors independently reviewed articles. We assessed for risk of bias using the Newcastle-Ottawa Quality Assessment Scale and the Cochrane Risk of Bias Tool and calculated pooled effects using random effects models. RESULTS We included 23 articles (22 observational studies and 1 randomized controlled trial), studying 1,121,582 subjects. There was no increased odds of fracture in VKA users versus controls (pooled OR 1.01, 95% CI 0.89, 1.14) or in VKA users versus NOAC users (pooled OR 0.95, 95% CI 0.78, 1.15). Subjects using a VKA for 1 year or longer did not have increased odds of fracture (pooled OR 1.07, 95% CI 0.90, 1.27). Compared to controls, there was increased odds of fracture in women (pooled OR 1.11, 95% CI 1.02, 1.21) and older VKA users (≥ 65) (pooled OR 1.07, 95% CI 1.01, 1.14). DISCUSSION We found no increase in odds of fracture in VKA users versus controls or NOAC users. There was a small increase in odds of fracture among female and elderly VKA users, which may not be clinically important when accounting for other considerations in choosing an anticoagulant. Our findings suggest that, when anticoagulation is necessary, fracture risk should not be a major consideration in choice of an agent. Future studies directly comparing VKA to NOAC users and studies with longer duration of VKA use may be needed.
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Affiliation(s)
- Wendy Fiordellisi
- Division of General Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
| | - Katherine White
- Division of General Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - Marin Schweizer
- Division of General Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.,Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA
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27
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Sawicka-Powierza J, Jablonska E, Ratajczak-Wrona W, Rogowska-Szadkowska D, Garley M, Oltarzewska AM, Chlabicz S, Konstantynowicz J. Bone Metabolism Markers and Bone Mineral Density in Patients on Long-Term Acenocoumarol Treatment: A Cross-Sectional Study. J Clin Med 2018; 7:jcm7100372. [PMID: 30347817 PMCID: PMC6209941 DOI: 10.3390/jcm7100372] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 10/17/2018] [Accepted: 10/18/2018] [Indexed: 11/16/2022] Open
Abstract
The aim of this study was to evaluate levels of osteocalcin (OC), osteoprotegerin (OPG) and total soluble receptor activator of nuclear factor-κB ligand (RANKL), and bone mineral density (BMD) in patients on long-term acenocoumarol (AC) treatment. The cross-sectional study was carried out in 42 patients treated long-term with AC and 28 control subjects. Serum concentrations of OC, OPG, and sRANKL were measured using enzyme linked immunosorbent assay (ELISA) kits, and BMD at the femoral neck and lumbar spine were assessed by dual energy X-ray absorptiometry. A significantly decreased concentration of OC was found in AC users compared to control subjects (4.94 ± 2.22 vs. 10.68 ± 4.5; p < 0.001). Levels of OPG, sRANKL logarithm (log), sRANKL/OPG log ratio, and BMD were comparable between. In female AC users, positive correlations between OC and RANKL log, and between OC and RANKL/OPG log ratio (p = 0.017; p = 0.005, respectively), and a negative correlation between OC and OPG (p = 0.027) were found. Long-term AC anticoagulation significantly decreases OC concentration, but does not affect other bone metabolism markers or BMD. Our results also suggest the possibility that long-term treatment with AC may alleviate bone resorption in postmenopausal women.
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Affiliation(s)
- Jolanta Sawicka-Powierza
- Department of Family Medicine, Medical University of Bialystok, Bialystok 15-054, Poland.
- Department of Haematology, Medical University of Bialystok, Bialystok 15-276, Poland.
| | - Ewa Jablonska
- Department of Immunology, Medical University of Bialystok, Bialystok 15-269, Poland.
| | | | | | - Marzena Garley
- Department of Immunology, Medical University of Bialystok, Bialystok 15-269, Poland.
| | - Alicja M Oltarzewska
- Department of Family Medicine, Medical University of Bialystok, Bialystok 15-054, Poland.
| | - Slawomir Chlabicz
- Department of Family Medicine, Medical University of Bialystok, Bialystok 15-054, Poland.
| | - Jerzy Konstantynowicz
- Department of Pediatric Rheumatology, Immunology, and Metabolic Bone Diseases, Medical University of Bialystok, Bialystok 15-274, Poland.
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Nguyen KD, Bagheri B, Bagheri H. Drug-induced bone loss: a major safety concern in Europe. Expert Opin Drug Saf 2018; 17:1005-1014. [DOI: 10.1080/14740338.2018.1524868] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- Khac-Dung Nguyen
- Laboratoire de Pharmacologie Médicale et Clinique, Equipe de Pharmacoépidémiologie de l’UMR INSERM 1027, Faculté de Médecine de l’Université Paul-Sabatier et Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d’Information sur le Médicament de l’UMR INSERM 1027, Centre Hospitalier Universitaire, Toulouse, France
- The National Centre of Drug Information and Adverse Drug Reaction Monitoring, Hanoi University of Pharmacy, Hanoi, Vietnam
| | - Bahador Bagheri
- Cancer Research Center and Department of Pharmacology, Semnan University of Medical Sciences, Semnan, Iran
| | - Haleh Bagheri
- Laboratoire de Pharmacologie Médicale et Clinique, Equipe de Pharmacoépidémiologie de l’UMR INSERM 1027, Faculté de Médecine de l’Université Paul-Sabatier et Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d’Information sur le Médicament de l’UMR INSERM 1027, Centre Hospitalier Universitaire, Toulouse, France
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Gundlund A, Fosbøl EL, Gislason GH, Olesen JB. Reply: Oral anticoagulation and hip fracture risk: a common misconception? J Intern Med 2018; 284:323-324. [PMID: 29797617 DOI: 10.1111/joim.12774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- A Gundlund
- Department of Cardiology S, University Hospital of Copenhagen, Herlev-Gentofte Hospital, Hellerup, Denmark
| | - E L Fosbøl
- Department of Cardiology, University Hospital of Copenhagen, Rigshospitalet, Denmark
| | - G H Gislason
- Department of Cardiology S, University Hospital of Copenhagen, Herlev-Gentofte Hospital, Hellerup, Denmark.,The Danish Heart Foundation, Copenhagen K, Denmark.,The National Institute of Public Health, University of Southern, Denmark
| | - J B Olesen
- Department of Cardiology S, University Hospital of Copenhagen, Herlev-Gentofte Hospital, Hellerup, Denmark
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30
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Hurley DL, Binkley N, Camacho PM, Diab DL, Kennel KA, Malabanan A, Tangpricha V. THE USE OF VITAMINS AND MINERALS IN SKELETAL HEALTH: AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND THE AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT. Endocr Pract 2018; 24:915-924. [PMID: 30035621 DOI: 10.4158/ps-2018-0050] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
ABBREVIATIONS 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; CV = cardiovascular; GI = gastrointestinal; IOM = Institute of Medicine; PTH = parathyroid hormone; RCT = randomized controlled trial; αTF = α-tocopherol; ucOC = undercarboxylated osteocalcin; VKA = vitamin K antagonist; WHI = Women's Health Initiative.
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31
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Green BN, Johnson CD, Haldeman S, Griffith E, Clay MB, Kane EJ, Castellote JM, Rajasekaran S, Smuck M, Hurwitz EL, Randhawa K, Yu H, Nordin M. A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders. PLoS One 2018; 13:e0197987. [PMID: 29856783 PMCID: PMC5983449 DOI: 10.1371/journal.pone.0197987] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 05/11/2018] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. METHODS A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. RESULTS Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers' compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. CONCLUSION Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature.
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Affiliation(s)
- Bart N. Green
- Qualcomm Health Center, Stanford Health Care, San Diego, California, United States of America
- Publications Department, National University of Health Sciences, Lombard, Illinois, United States of America
| | - Claire D. Johnson
- Publications Department, National University of Health Sciences, Lombard, Illinois, United States of America
| | - Scott Haldeman
- Department of Neurology, University of California, Irvine, California, United States of America
- Department of Epidemiology, School of Public Health, University of California, Los Angeles, California, United States of America
- World Spine Care, Santa Ana, California, United States of America
| | - Erin Griffith
- Emergency Medicine, Carlsbad, California, United States of America
| | - Michael B. Clay
- Rehabilitation Care Line, Physical Medicine and Rehabilitation, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, United States of America
| | - Edward J. Kane
- College of Rehabilitative Sciences, Doctor of Physical Therapy Program, University of St. Augustine for Health Sciences, San Marcos, California, United States of America
| | - Juan M. Castellote
- National School of Occupational Medicine, Carlos III Institute of Health, Complutense University of Madrid, Madrid, Spain
| | | | - Matthew Smuck
- Section of Physical Medicine and Rehabilitation and Department of Orthopaedic Surgery, Stanford University, Redwood City, California, United States of America
| | - Eric L. Hurwitz
- Office of Public Health Studies, University of Hawai`i, Mānoa, Honolulu, Hawaii, United States of America
| | - Kristi Randhawa
- UOIT-CMCC Centre for Disability Prevention and Rehabilitation, University of Ontario Institute of Technology, Toronto, Ontario, Canada
- Department of Undergraduate Education, Canadian Memorial Chiropractic College, Toronto, Ontario, Canada
| | - Hainan Yu
- UOIT-CMCC Centre for Disability Prevention and Rehabilitation, University of Ontario Institute of Technology, Toronto, Ontario, Canada
| | - Margareta Nordin
- World Spine Care, Santa Ana, California, United States of America
- Department of Orthopedic Surgery, New York University, New York, New York, United States of America
- Department of Environmental Medicine, New York University, New York, New York, United States of America
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Watts NB. Adverse bone effects of medications used to treat non-skeletal disorders. Osteoporos Int 2017; 28:2741-2746. [PMID: 28752332 DOI: 10.1007/s00198-017-4171-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Accepted: 07/20/2017] [Indexed: 12/11/2022]
Abstract
There is a growing list of medications used to treat non-skeletal disorders that cause bone loss and/or increase fracture risk. This review discusses glucocorticoids, drugs that reduce sex steroids, antidiabetic agents, acid-reducing drugs, selective serotonin reuptake inhibitors, and heparin. A number of drugs are known to cause bone loss, increase fracture risk, or both. These drugs should be used in the lowest dose necessary to achieve the desired benefit and for the shortest time necessary, but in many cases, long-term treatment is required. Effective countermeasures are available for some.
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Affiliation(s)
- N B Watts
- Mercy Health Osteoporosis and Bone Health Services, 4760 E. Galbraith Rd., Suite 212, Cincinnati, OH, 45236, USA.
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Suzuki Y, Maruyama-Nagao A, Sakuraba K, Kawai S. Level of serum undercarboxylated osteocalcin correlates with bone quality assessed by calcaneal quantitative ultrasound sonometry in young Japanese females. Exp Ther Med 2017; 13:1937-1943. [PMID: 28565790 DOI: 10.3892/etm.2017.4206] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Accepted: 01/03/2017] [Indexed: 01/23/2023] Open
Abstract
The diagnostic criteria of osteoporosis were established based on bone mineral density (BMD). Therefore, BMD measured by dual energy X-ray absorptiometry has been recognized as the gold standard to diagnose osteoporosis. However, discrepancies between fracture risk and BMD have been recognized. Bone is composed of collagen scaffold reinforced by hydroxyapatite. Both protein scaffold and hydroxyapatite are involved in bone quality. BMD may indicate bone mineralization but potentially fail to assess the protein scaffold. Vitamin K contributes to bone mineralization and as a protein scaffold. A deficiency of vitamin K upregulates the level of serum undercarboxylated osteocalcin (ucOC), and serum ucOC correlates with fracture risk. However, direct association of ucOC and bone quality has not been demonstrated. For the present study, a total of 49 healthy young Japanese female college students underwent calcaneal; quantitative ultrasound sonometry (QUS) and determination of serological bone metabolic markers. QUS parameters were significantly correlated with serum 25-hydroxyvitamin D (25-OH-D) concentrations (P<0.05). A significant negative correlation was also identified between log transformed serum ucOC concentrations [Ln(ucOC)] and a QUS parameter, speed of sound (SOS) (P<0.05). Stepwise multiple regression analysis indicated that Ln(ucOC) was an independent determinant of SOS, and 25-OH-D was an independent determinant of the other two QUS parameters, transmission index (TI) and synthetic parameter osteo-sono-assessment index. As vitamin D is involved in bone mineralization, TI may reflect the mineralization. Correlation of vitamin K status, indicated by ucOC, with SOS may clarify the correlation between vitamin K status and bone quality, although the material factors that connect them have not been identified.
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Affiliation(s)
- Yoshio Suzuki
- Graduate School of Health and Sports Science, Juntendo University, Inzai, Chiba 270-1695, Japan
| | - Asako Maruyama-Nagao
- School of Health and Sports Science, Juntendo University, Inzai, Chiba 270-1695, Japan
| | - Keishoku Sakuraba
- Graduate School of Health and Sports Science, Juntendo University, Inzai, Chiba 270-1695, Japan
| | - Sachio Kawai
- Graduate School of Health and Sports Science, Juntendo University, Inzai, Chiba 270-1695, Japan
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Sugiyama T, Oda H. Edoxaban Versus Warfarin: Bone Fractures Due to Falling. J Am Coll Cardiol 2017; 69:466-467. [PMID: 28126164 DOI: 10.1016/j.jacc.2016.10.071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 10/11/2016] [Indexed: 11/17/2022]
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Luchini C, Stubbs B, Solmi M, Veronese N. Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale. World J Meta-Anal 2017; 5:80. [DOI: 10.13105/wjma.v5.i4.80] [Citation(s) in RCA: 542] [Impact Index Per Article: 67.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 02/22/2017] [Accepted: 06/08/2017] [Indexed: 02/06/2023] Open
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Sugiyama T, Kono Y, Sekiguchi K, Kim YT, Oda H. An evidence-based perspective on warfarin and the growing skeleton. Osteoporos Int 2016; 27:2883-2884. [PMID: 27091741 DOI: 10.1007/s00198-016-3588-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 03/30/2016] [Indexed: 12/11/2022]
Affiliation(s)
- T Sugiyama
- Department of Orthopaedic Surgery, Saitama Medical University, 38 Morohongo, Moroyama, Saitama, 350-0495, Japan.
| | - Y Kono
- Department of Orthopaedic Surgery, Saitama Medical University, 38 Morohongo, Moroyama, Saitama, 350-0495, Japan
| | - K Sekiguchi
- Department of Orthopaedic Surgery, Saitama Medical University, 38 Morohongo, Moroyama, Saitama, 350-0495, Japan
| | - Y T Kim
- Department of Orthopaedic Surgery, Saitama Medical University, 38 Morohongo, Moroyama, Saitama, 350-0495, Japan
| | - H Oda
- Department of Orthopaedic Surgery, Saitama Medical University, 38 Morohongo, Moroyama, Saitama, 350-0495, Japan
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Veronese N, Bano G, Granziera S, Solmi M, Cohen AT, Correll CU. Vitamin K antagonists' use and fracture risk: results from a systematic review and meta-analysis: reply. J Thromb Haemost 2016; 14:221-3. [PMID: 26554746 DOI: 10.1111/jth.13180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Affiliation(s)
- N Veronese
- Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy
| | - G Bano
- Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy
| | - S Granziera
- Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy
| | - M Solmi
- Department of Neurosciences, University of Padova, Padova, Italy
- National Research Council, Aging Branch, Institute of Neuroscience, Padova, Italy
| | - A T Cohen
- Department of Haematological Medicine, Guys and St Thomas' NHS Foundation Trust, London, UK
| | - C U Correll
- The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, New York, USA
- Hofstra North Shore LIJ School of Medicine, Hempstead, New York, USA
- The Feinstein Institute for Medical Research, Manhasset, New York, USA
- Albert Einstein College of Medicine, Bronx, New York, USA
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Zhao SS, Lin ZY, Zhu Y. Vitamin K antagonists' use and fracture risk: results from a systematic review and meta-analysis: comment. J Thromb Haemost 2016; 14:219-21. [PMID: 26663818 DOI: 10.1111/jth.13192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 11/04/2015] [Indexed: 12/01/2022]
Affiliation(s)
- S S Zhao
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
| | - Z Y Lin
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
| | - Y Zhu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
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