title: Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Arthritis Research Campaign Epidemiology Unit, Division of Epidemiology and Health Sciences, University of Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Thornton
authors.forename: D M
authors.initials: DM
authors.lastname: Ashcroft
authors.forename: M Z
authors.initials: MZ
authors.lastname: Mughal
authors.forename: R A
authors.initials: RA
authors.lastname: Elliott
authors.forename: T W
authors.initials: TW
authors.lastname: O'Neill
authors.forename: D
authors.initials: D
authors.lastname: Symmons
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000150:complications*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002648:Child; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D010013:Osteogenesis Imperfecta / Q000150:complications / Q000188:drug therapy; D010024:Osteoporosis / Q000150:complications / Q000188:drug therapy*
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates