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Published on: April 14, 2016
Optimizing bone health with bisphosphonate therapies in pediatric osteogenesis imperfecta: a network meta-analysis of
Ying-Yu Wang1, Yu-Cheng Su2, Pei-Chun Lai3
1Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan.
Insights
Pamidronate improved bone density, zoledronic acid improved Z-scores, but both had limitations in treating pediatric osteogenesis imperfecta (OI). Further trials are needed for fracture prevention and optimal bisphosphonate therapy.
Area of Science:
- Pediatric Endocrinology
- Metabolic Bone Diseases
- Pharmacological Treatments
Background:
- Optimal bisphosphonate treatment for pediatric osteogenesis imperfecta (OI) is not well-established.
- This study addresses the uncertainty by comparing various bisphosphonate therapies in children with OI.
Purpose of the Study:
- To conduct a network meta-analysis (NMA) comparing the effectiveness of different bisphosphonate therapies for pediatric OI.
- To evaluate outcomes including bone mineral density, Z-scores, bone turnover markers, fracture rates, and adverse events.
Main Methods:
- A PRISMA-guided network meta-analysis (NMA) of randomized controlled trials (RCTs) involving oral or intravenous bisphosphonates in pediatric OI.
- Primary outcomes: changes in lumbar spine areal bone mineral density (LS-aBMD) and Z-scores at 1 and 2 years, and fracture events.
- Secondary outcomes: bone turnover markers (uNTX/Cr) and adverse event rates at 1 and 2 years.
Main Results:
- The NMA included 9 RCTs with 595 children. At 2 years, pamidronate showed the greatest LS-aBMD improvement versus placebo. Zoledronic acid yielded superior LS Z-scores at 1 and 2 years but had higher adverse event rates.
- Olpadronate was the only bisphosphonate to reduce total fracture numbers compared to placebo. Alendronate maintained bone turnover marker reduction at 2 years.
Conclusions:
- Pamidronate demonstrated superior LS-aBMD improvements, while zoledronic acid showed the most significant Z-score gains but increased adverse events.
- Evidence gaps exist for fracture prevention and bone turnover markers, necessitating large-scale, head-to-head trials comparing oral and IV bisphosphonates for pediatric OI.
Abstract:
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.
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