Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis

Abstract

Aims: To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions. Methods: Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis. Results: Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles. Conclusions: Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role.

Bone health in children and adolescents after allogeneic stem cell transplantation

“…38 Bisphosphonate therapy also has been used successfully in children. 39 However, the therapeutic approach in children should always begin with the correction of nutritional and hormonal deficiencies, including sex steroids and growth hormone. Bisphosphonates should be used cautiously and only by physicians familiar with this treatment.…”

Optimizing Bone Health in Children and Adolescents

“…Bisphosphonates inhibit osteoclastmediated bone resorption and have been used to increase BMD and reduce fracture risk in children with osteogenesis imperfecta, [119][120][121] cerebral palsy, 122 and connective tissue disorders 123,124 and children treated with corticosteroids. 123,[125][126][127] Pilot studies have also been conducted in adolescents with anorexia nervosa.…”

Linhas escleróticas metafisárias em crianças e adolescentes em uso de alendronato

“…[3][4][5][6][7] The main indications of bisphosphonates in childhood include: therapeutic failure of the treatment of low bone density for the chronologic age (Z score lower than or equal to -2.0 standard deviations); intolerance to the conventional treatment with calcium and vitamin D; or presence of fractures. 8,9 Its beneficial effects on bone density gain are well known; however, its long-term effects are unknown. Adverse effects, such as abdominal pain, diarrhea, nausea, dyspepsia, esophagitis, and exanthema have been described.…”