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Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year
Ralph Sakkers1, Dieke Kok, Raoul Engelbert
1Department of Orthopaedic Surgery, Wilhelmina Children's Hospital-University Medical Centre Utrecht, Utrecht, Netherlands. r.sakkers@wkz.azu.nl
Insights
Oral bisphosphonate olpadronate reduced long bone fractures by 31% in children with osteogenesis imperfecta. While effective for fracture risk, its long-term impact on the disease course requires further investigation.
Area of Science:
- Pediatric Endocrinology
- Orthopedics
- Pharmacology
Background:
- Osteogenesis imperfecta (OI) is a genetic disorder characterized by brittle bones.
- Previous non-randomized studies suggested bisphosphonates may benefit OI patients.
- This study investigated oral olpadronate's efficacy in pediatric OI.
Purpose of the Study:
- To evaluate the effect of oral olpadronate on fracture incidence in children with osteogenesis imperfecta.
- To assess changes in bone mineral content (BMC) and bone mineral density (BMD) with olpadronate treatment.
- To determine the impact of olpadronate on functional outcomes and bone resorption markers in pediatric OI.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 34 children with OI.
- Participants received either oral olpadronate (10 mg/m2 daily) or a placebo for 2 years, alongside calcium and vitamin D supplements.
- Primary endpoints included long bone fractures, BMC, BMD, and functional outcomes; analyses were intention-to-treat.
Main Results:
- Olpadronate treatment significantly reduced the relative risk of long bone fractures by 31% (p=0.01).
- The olpadronate group demonstrated significantly greater increases in spinal BMC and BMD compared to placebo.
- No significant effects were observed on functional outcomes, anthropometrics, vertebral height, or urinary bone resorption markers.
Conclusions:
- Daily oral olpadronate at 10 mg/m2 effectively reduces long bone fracture risk in children with osteogenesis imperfecta.
- The study provides evidence for olpadronate's benefit in improving bone density in pediatric OI.
- Further research is necessary to determine if bisphosphonates can alter the overall natural progression of osteogenesis imperfecta.
Background:
Non-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial.
Methods:
34 children recruited from the Dutch national centre for osteogenesis imperfecta were randomly assigned olpadronate (10 mg/m2 daily; n=16) or placebo (n=18) for 2 years. All children also received calcium and vitamin D supplements. Primary endpoints were incident fractures of long bones and changes in bone mineral content (BMC), bone mineral density (BMD), and functional outcome. Anthropometry, vertebral height, and urinary markers of bone resorption were also studied. Analyses were by intention to treat.
Findings:
Fracture follow-up was complete for all the children, including two who withdrew from the study (one from each group). Olpadronate treatment was associated with a 31% reduction in relative risk of fracture of long bones (hazard ratio 0.69 [95% CI 0.52-0.91], p=0.01). The olpadronate group showed significantly greater increases than the placebo group in spinal BMC (difference between groups 2.24 g/year [0.20-4.29], p=0.03) and spinal BMD (difference between groups 0.054 g/cm2 per year [0.012-0.096], p=0.01). There were no detectable effects on functional outcome, anthropometrics, or vertebral height and no differences between the groups in changes in urinary markers of bone resorption.
Interpretation:
Oral treatment with olpadronate at a daily dose of 10 mg/m2 results in a reduction of fracture risk of long bones in children with osteogenesis imperfecta. However, the issue of whether bisphosphonates will alter the natural course of osteogenesis imperfecta remains unresolved, and further studies are needed.
