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Lookup NU author(s): Dr Terry AsprayORCiD, Dr Stephen Tuck
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© 2026 American Medical Association.Importance: Osteogenesis imperfecta causes multiple fractures throughout life, causing substantial morbidity. Objective: To determine whether the parathyroid hormone analogue teriparatide followed by zoledronic acid reduces the risk of fractures in adults with osteogenesis imperfecta. Design, Setting, and Participants: Multicenter open-label, parallel-group, randomized clinical trial, conducted between May 17, 2017, and March 21, 2025, in adults attending one of 27 referral centers with a clinical diagnosis of osteogenesis imperfecta. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone turnover by serum procollagen type 1 N-terminal propeptide and C-terminal telopeptide of type 1 collagen. Fractures were confirmed by skeletal imaging. Several measures of health-related quality of life were assessed. Interventions: Those in the active group received 20 μg of teriparatide daily by subcutaneous injection for 2 years followed by an infusion of 5 mg of zoledronic acid. In the standard care group, bisphosphonates and other bone-targeted medicines could be used but teriparatide and other bone anabolic drugs were prohibited. Main outcomes and measures: The primary end point was the number of participants with imaging-proven incident fractures adjudicated by reviewers blinded to treatment allocation. Secondary end points included the total number of fractures, changes in BMD, biochemical markers of bone turnover, and health-related quality of life. Results: Of the 350 individuals randomized, 176 were allocated to receive teriparatide plus zoledronic acid, 174 to standard care, and 1 withdrew, leaving 349 evaluable participants. The mean age was 43.7 years (188 females [53.9%]). Most had type I osteogenesis imperfecta caused by pathogenic variants in the type 1 collagen genes. In the teriparatide plus zoledronic acid group 65 of 176 (36.9%) had incident fractures compared with 63 of 173 (36.4%) in the standard care group (absolute risk reduction, -1.57%; 95% CI, -9.90% to 5.89%; hazard ratio, 0.97; 95% CI, 0.68 to 1.38). Lumbar spine and total hip BMD increased significantly more with teriparatide plus zoledronic acid than standard care. Several quality-of-life measures favored teriparatide plus zoledronic acid. Adverse events were similar in both groups. Conclusions and Relevance: This randomized clinical trial among adults with osteogenesis imperfecta found that teriparatide plus zoledronic acid did not reduce fracture risk compared with standard care despite significantly increasing BMD, suggesting the importance of reduced bone quality rather than low bone density in the pathogenesis of fracture.
Author(s): Hald JD, Weir CJ, Keerie C, Dewar L, Maclean M, Milne L, Keen R, Walsh JS, Poole KES, Langdahl BL, Lindsay JR, Ghouri N, Hollick R, Aspray T, Crowley RK, Cohen-Solal M, Hassan-Smith Z, Tuck S, Curtis EM, Harvey NC, Eekhoff EMW, Feenstra J, Hampson G, Stone M, Turton J, Patel P, Siddiqi M, Munro R, Roy M, Paskins Z, Narayanan D, Malcolm E, Javaid MK, Osborne P, Tang JCY, Lam W, Moore D, Black HA, Duckworth AD, Makaram NS, Guo T, Stenhouse G, Ralston SH
Publication type: Article
Publication status: Published
Journal: JAMA
Year: 2026
Pages: epub ahead of print
Online publication date: 14/05/2026
Acceptance date: 13/04/2026
ISSN (print): 0098-7484
ISSN (electronic): 1538-3598
Publisher: American Medical Association
URL: https://doi.org/10.1001/jama.2026.6889
DOI: 10.1001/jama.2026.6889
PubMed id: 42133304
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