Optimizing bone health with bisphosphonate therapies in pediatric osteogenesis imperfecta: a network meta-analysis of randomized trials

Summary

This study compares the efficacy of various bisphosphonate treatments for pediatric osteogenesis imperfecta (OI) in terms of lumbar spine areal bone mineral density (LS-aBMD), Z-scores, bone turnover markers (BTMs), fracture rates, and adverse events.

Purpose

The optimal bisphosphonate treatment for pediatric OI remains uncertain. This study aims to analyze the comparative effectiveness of different bisphosphonate therapies for children with OI.

Methods

A network meta-analysis (NMA) was conducted following PRISMA guidelines, screening clinical trials involving oral or intravenous bisphosphonate therapy in pediatric OI. The primary outcomes included changes in LS-aBMD and Z-scores over 1 and 2 years and fracture events. Secondary outcomes included BTM (uNTX/Cr) over 1 and 2 years and adverse event rates.

Results

The NMA included 9 RCTs with 595 children. For LS-aBMD changes, no bisphosphonates showed differences at 1 year; at 2 years, all active treatments improved LS-aBMD compared to placebo, with pamidronate showing greatest improvement (208.73 mg/cm², 95% CI 60.48, 356.98; CoE, moderate). Zoledronic acid demonstrated superior LS Z-scores at both 1 year (1.63 points, 95% CI 0.07, 3.19; CoE, low) and 2 years (1.37 points, 95% CI 0.95, 1.79; CoE, low). In the limited fracture analysis, only olpadronate reduced total fracture numbers compared to placebo (− 1.65, 95% CI − 3.05, − 0.26; CoE, moderate). For BTMs, all treatments reduced 1-year uNTX/Cr versus placebo, with only alendronate maintaining reduction at 2 years (− 182.38 nmol/mmol, 95% CI − 283.67, − 81.09; CoE, moderate). Zoledronic acid showed higher adverse event rates versus placebo (5.49, 95% CI 1.66, 18.19; CoE, low).

Conclusion

Among various bisphosphonates, pamidronate demonstrated superior improvements in LS-aBMD, while zoledronic acid achieved the most substantial Z-score gains but exhibited increased adverse event rates. Evidence gaps, particularly in direct comparative trials, limit definitive conclusions regarding fracture prevention and bone turnover markers. Future large-scale head-to-head trials comparing oral and intravenous formulations are essential to establish evidence-based treatment protocols for pediatric osteogenesis imperfecta.

Trial registration.

This research is registered with PROSPERO, registration number CRD42024571408.