Oral Bisphosphonate Therapy for Osteogenesis Imperfecta: A Systematic Review and Meta‐Analysis of Six Randomized Placebo‐Controlled Trials

OBJECTIVE: To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients with osteogenesis imperfecta (OI). METHODS: Studies were eligible for inclusion if they were randomized controlled trials of directly comparing oral bisphosphonate therapy with placebo‐group in OI patients. Data synthesis regarding to bone mineral density as measured by dual‐energy X‐ray absorptiometry (DEXA), decreased fracture incidence, change in biochemical markers of bone and mineral metabolism, bone histology, growth, bone pain, quality of life, and others were assessed, and meta‐analysis done when possible. RESULTS: From 98 potential references and six randomized controlled studies a total of 263 participants receiving oral bisphosphonates and 143 placebo treatments contributed data to meta‐analysis. Pooled meta‐analysis of three studies suggested that there was significant difference between bisphosphonate treated group and placebo in number of patients with at least one fracture (mean difference 0.53, 95% confidence interval 0.32–0.89, P = 0.02). Pooled meta‐analysis of two studies suggested that significant difference was noted between bisphosphonate treated group and placebo in mean percentage change in spine BMD (T‐score) (mean difference 28.43, 95% confidence interval 7.09‐49.77, P = 0.009). The similar effect was shown in the term of mean change (Z‐score) in spine BMD. CONCLUSIONS: Significant improvement in lumbar areal BMD in patients affected with OI has been shown when treated with oral bisphosphonates, even though only a small population was enrolled. We cannot draw a definite conclusion that the increase in BMD can be translated into fracture reduction and clinical functional improvement. The optimal method, dose, type, initiation, and duration of oral bisphosphonates therapy still remains unclear. Well‐designed, adequately‐powered, placebo‐controlled RCTs investigating the effects of oral bisphosphonates on fractures reduction and improvement in quality of life in both children and adults are studied here.