Teriparatide plus zoledronic acid may increase BMD but may not Reduce Fractures in Osteogenesis Imperfecta: Study
Researchers have found in a new randomized clinical trial in adults with osteogenesis imperfecta that teriparatide plus zoledronic acid significantly increased bone mineral density (BMD) but did not reduce fracture risk compared with standard care. The findings suggest that impaired bone quality, rather than low bone density alone, plays a key role in fracture risk in osteogenesis imperfecta. The study was published in JAMA by Jannie D. and colleagues.
In order to determine if an aggressive combination treatment can prevent skeletal failure in the at-risk cohort, the researchers carried out an open-label, parallel-group randomized clinical trial through an international consortium of 27 elite referral centers. The longitudinal study involved adult subjects within a multiyear period beginning from May 17, 2017, to March 21, 2025. The design of the clinical trial divided the study participants into two groups: active intervention group and standard care control group. Participants allocated to the active intervention group were given a daily subcutaneous dose of 20 micrograms of parathyroid hormone analog teriparatide over a span of 2 years before getting a single intravenous dose of 5 mg of zoledronic acid.
On the other hand, subjects enrolled in the standard care control group were treated with standard treatments such as conventional bisphosphonates; however, any use of bone anabolic drugs was completely banned. Changes in the skeletal structure were assessed with dual-energy X-ray absorptiometry (DXA) in order to measure bone mineral density (BMD), along with serum procollagen type 1 N-terminal propeptide and C-terminal telopeptide levels in monitoring metabolic bone remodeling.
Key findings:
- The international clinical trial was successful in randomizing a total baseline sample of 350 adult subjects with a definite diagnosis of osteogenesis imperfecta.
- After the exclusion of exactly 1 subject, the total analytical cohort was found to consist of 349 evaluable subjects aged on average 43.7 years, out of which 188 females (53.9%).
- Among those exposed to the experimental treatment, exactly 65 out of 176 subjects (36.9%) were identified with new imaging-based fractures during the study period.
- Out of 173 subjects in the standard control group, exactly 63 (36.4%) subjects developed new fractures with no significant difference in the therapy.
- The calculated absolute risk reduction and hazard ratio were 0% (95% CI, -9.90 to 5.89%) and 0.97 (95% CI, 0.68 to 1.38), respectively.
This randomized controlled trial conducted on adults with OI concluded that the combination of teriparatide and zoledronic acid failed to decrease fracture risks compared to standard treatment although there was a significant increase in bone mineral density, highlighting the role of poor bone quality as opposed to low bone density in fracture etiology. The results serve as an indispensable basis for contemporary metabolic bone science, demonstrating the necessity of correction of bone matrix defects as opposed to merely piling up minerals.
Reference:
Hald JD, Weir CJ, Keerie C, et al. Teriparatide Plus Zoledronic Acid for Osteogenesis Imperfecta: A Randomized Clinical Trial. JAMA. 2026;336(2):116–124. doi:10.1001/jama.2026.6889
