Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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J. Bone Miner. Res. · Nov 2019
Randomized Controlled Trial Comparative StudyPain at Multiple Sites Is Associated With Prevalent and Incident Fractures in Older Adults.
Musculoskeletal pain is common and typically occurs at multiple sites. Pain has been shown to be associated with falls risk; however, whether an increased risk for falls associated with multisite pain (MSP) translates into an increased risk of fractures has not been investigated. This study aimed to examine the association of number of painful sites with prevalent and incident fractures. ⋯ These associations remained statistically significant after further adjustment for falls risk and BMD. Pain at multiple sites was associated with incident fracture risk in a dose-response manner, suggesting that widespread pain is an independent contributor to fracture risk. The potential for pain management in fracture prevention warrants further exploration. © 2019 American Society for Bone and Mineral Research.
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J. Bone Miner. Res. · Aug 2018
Randomized Controlled TrialA Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis.
In X-linked hypophosphatemia (XLH), inherited loss-of-function mutations in the PHEX gene cause excess circulating levels of fibroblast growth factor 23 (FGF23), leading to lifelong renal phosphate wasting and hypophosphatemia. Adults with XLH present with chronic musculoskeletal pain and stiffness, short stature, lower limb deformities, fractures, and pseudofractures due to osteomalacia, accelerated osteoarthritis, dental abscesses, and enthesopathy. Burosumab, a fully human monoclonal antibody, binds and inhibits FGF23 to correct hypophosphatemia. ⋯ There were no treatment-related serious adverse events or meaningful changes from baseline in serum or urine calcium, intact parathyroid hormone, or nephrocalcinosis. These data support the conclusion that burosumab is a novel therapeutic addressing an important medical need in adults with XLH.© 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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J. Bone Miner. Res. · Feb 2018
Randomized Controlled Trial Comparative StudySerum Sclerostin Levels in Adults With Osteogenesis Imperfecta: Comparison With Normal Individuals and Response to Teriparatide Therapy.
Sclerostin (SOST), a glycoprotein primarily derived from osteocytes, is an important regulator of bone remodeling. Osteogenesis imperfecta (OI) is a heritable disorder of bone characterized by low bone mass, bone fragility, recurrent fractures, and bone deformities. Altered SOST-mediated signaling may have a role in pathogenesis of type I collagen-related OI; however, this has not been evaluated in humans. ⋯ The increase was significant at 6, 12, and 24 months of therapy (p ≤ 0.02) and was apparent as early as 3 months (p = 0.06). The magnitude of increases in SOST levels during therapy was inversely correlated with increases in vertebral volumetric bone mineral density (vBMD). Overall, these results suggest that: 1) SOST regulation is fundamentally altered in osteogenesis imperfecta; 2) serum SOST levels could be a biomarker of OI in adults; and 3) alterations in SOST may help predict the response to anabolic therapies in OI. © 2017 American Society for Bone and Mineral Research.
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J. Bone Miner. Res. · Jan 2015
Randomized Controlled Trial Comparative StudyComparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: the DATA-HRpQCT Study.
Combined teriparatide and denosumab increases spine and hip bone mineral density more than either drug alone. The effect of this combination on skeletal microstructure and microarchitecture, however, is unknown. Because skeletal microstructure and microarchitecture are important components of skeletal integrity, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) assessments at the distal tibia and radius in postmenopausal osteoporotic women randomized to receive teriparatide 20 µg daily (n = 31), denosumab 60 mg every 6 months (n = 33), or both (n = 30) for 12 months. ⋯ In the teriparatide group, radial cortical porosity increased by 20.9 ± 37.6% and by 5.6 ± 9.9% at the tibia but did not change in the other two groups. Bone stiffness and failure load, as estimated by finite element analysis, did not change in the teriparatide group but increased in the other two groups at both sites. Together, these findings suggest that the use of denosumab and teriparatide in combination improves HR-pQCT measures of bone quality more than either drug alone and may be of significant clinical benefit in the treatment of postmenopausal osteoporosis.
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J. Bone Miner. Res. · Jun 2014
Randomized Controlled TrialPamidronate attenuates muscle loss after pediatric burn injury.
Children who are burned >40% total body surface area lose significant quantities of both bone and muscle mass because of acute bone resorption, inflammation, and endogenous glucocorticoid production, which result in negative nitrogen balance. Because administration of the bisphosphonate pamidronate within 10 days of the burn injury completely prevents the bone loss, we asked whether muscle protein balance was altered by the preservation of bone. We reviewed the results from 17 burned pediatric subjects previously enrolled in a double-blind randomized controlled study of pamidronate in the prevention of post-burn bone loss and who were concurrently evaluated for muscle protein synthesis and breakdown by stable isotope infusion studies during the acute hospitalization. ⋯ Muscle fiber diameter was significantly greater in the pamidronate subjects and leg strength at 9 months post-burn was not different between subjects who received pamidronate and normal physically fit age-matched children studied in our lab. Leg strength in burned subjects who served as controls tended to be weaker, although not significantly so. If substantiated by a larger study, these results suggest that bone may have a paracrine mechanism to preserve muscle and this finding may have implications for the treatment of sarcopenia in the elderly.