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A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease management Thornton J; Ashcroft D; O'Neill T; Elliott R; Adams J; Roberts C; Rooney M; Symmons DHealth Technol Assess 2008[Mar]; 12 (3): iii-ix, xi-xiv, 1-208OBJECTIVES: To review outcome measures and treatment costs in children with juvenile idiopathic arthritis (JIA) and low bone mineral density (BMD) and/or fragility fractures. To review evidence for effectiveness and safety of bisphosphonates and calcium and/or vitamin D in these children. To assess long-term bone health in adults with JIA. DATA SOURCES: Major databases were searched up to July 2005 for effectiveness studies and up to January 2005 for costs. REVIEW METHODS: A structured search strategy was conducted. For the evaluation of long-term bone health, outcome data were derived from two cohorts of adult patients with JIA. As there were few published cost data, an ongoing UK longitudinal study (CAPS) provided background data on the cost of managing JIA. RESULTS: Sixteen studies (78 children with JIA) were included. At baseline, the children had BMD below the expected values for age- and sex-matched children; treatment with bisphosphonates increased BMD with mean percentage increases in spine BMD varying from 4.5 to 19.1%. None of the studies with control groups compared results between the intervention and control groups, they only compared each group with its own baseline. Overall, studies were heterogeneous in design, of variable quality and with no consistency in methods of assessing and reporting outcomes. Hence, data could not be combined or an effect size calculated. A further 43 papers were included in the safety review; side-effects were generally transient. Two studies assessed treatment with calcium and/or vitamin D; BMD was increased from 0.75 to 0.830 g/cm2 after 6 months and BMD Z-score from -2.8 to -2.3 after 6 months and -2.4 after 1 year. There are relatively few long-term studies on the occurrence of low BMD and fragility fractures in children with JIA, with most studies only following children for 1 or 2 years. However, the long- and short-term data indicate that children with JIA have a lower BMD and more fractures than children without JIA. There are very few data on long-term bone health from adults who have JIA, but studies indicate that low BMD persists into adulthood, although adults in remission from JIA may attain the same BMD as healthy adults. From the available data, any predictors of low BMD and fractures in children and adults with JIA remain uncertain. No studies were found that discussed the costs of treating children with JIA and low BMD and/or fragility fractures. In CAPS, 297 of 457 children with JIA attended a 12-month follow-up visit. The mean annual total cost per child in the first year after diagnosis was 1649 pounds (standard deviation 1093 pounds, range 401-6967 pounds). The highest cost component was appointments with paediatric rheumatologists. The study is continuing to accrue and follow up patients and further analyses will be undertaken as the study progresses. CONCLUSIONS: BMD, adjusted for size, should be assessed as the primary outcome in studies of bone health in children with JIA. Quantitative computed tomography could be used where equipment is available as it offers the advantage of measuring volumetric density. Bisphosphonates are a promising treatment for osteoporosis in children with JIA, but the quality of the current evidence is poor. The accurate assessment of outcome is crucial. There are still uncertainties about the use of bisphosphonates in children, including whether the positive effects of treatment continue over time, the length of treatment and the maximal bone mass gain that can be achieved. Adults with JIA may have persistent low BMD compared with an otherwise healthy population together with an increased risk of fracture. There are no studies evaluating the costs of treating children with JIA and low BMD and/or fragility fractures. There are few data evaluating the costs of treating JIA in general. In the first 12 months after diagnosis, children with all JIA disease subtypes consume large, but highly variable, quantities of health service resources, the largest component being the consultant rheumatology appointments. Data from a larger cohort, over a longer period, are required to substantiate these results further. Further research is needed to assess more clearly the role and permit licensing of bisphosphonates for treatment of children, and in particular, longer-term studies.|*Disease Management[MESH]|Absorptiometry, Photon[MESH]|Adolescent[MESH]|Adult[MESH]|Aged[MESH]|Arthritis, Juvenile/*complications/economics[MESH]|Calcium/therapeutic use[MESH]|Child[MESH]|Diphosphonates/therapeutic use[MESH]|Female[MESH]|Fractures, Bone/drug therapy/*prevention & control[MESH]|Humans[MESH]|Male[MESH]|Middle Aged[MESH]|Risk Assessment[MESH]|Risk Factors[MESH]|Time Factors[MESH]|Vitamin D/therapeutic use[MESH] |
