2026-05-14 エディンバラ大学
＜関連情報＞
- https://www.ed.ac.uk/news/treatment-shift-needed-for-brittle-bone-disease
- https://jamanetwork.com/journals/jama/fullarticle/2849063
骨形成不全症に対するテリパラチドとゾレドロン酸の併用療法 無作為化臨床試験 Teriparatide Plus Zoledronic Acid for Osteogenesis Imperfecta A Randomized Clinical Trial
Jannie Dahl Hald, PhD; Christopher J. Weir, PhD; Catriona Keerie, PhD;et al
Journal of the American Medical Association Published:May 14, 2026
DOI:10.1001/jama.2026.6889
Teriparatide Plus Zoledronic Acid vs Usual Care for Treating Osteogenesis Imperfecta
Visual Abstract.
Key Points
Question Can intervention with the parathyroid hormone analogue teriparatide followed by zoledronic acid reduce the risk of fractures in adults with osteogenesis imperfecta?
Findings In this randomized clinical trial, 65 of 176 participants (36.9%) allocated to receive teriparatide plus zoledronic acid had incident fractures compared with 63 of 173 participants (36.4%) allocated to receive standard care. This difference was not significant, despite significantly greater increases in bone density with teriparatide plus zoledronic acid.
Meaning Increasing bone density with teriparatide plus zoledronic acid did not prevent fractures in osteogenesis imperfecta, emphasizing that defects in bone quality may be more important than low bone density in the pathogenesis of fracture.
Abstract
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.
Trial Registration isrctn.org Identifier: ISRCTN15313991
