Significant generalized osteopenia develops during childhood or adolescence in some 40% of JRA patients. Attainment of life long peak bone mass occurs during adolescence for females and has been shown to be decreased in many JRA patients. There are neither accepted treatments nor controlled trials addressing osteopenia in JRA patients. Observational studies in JRA patients document high prevalence of suboptimal dietary intake of calcium (Ca) and vitamin D, significantly lower gastrointestinal Ca absorption and low bone formation rate. In JRA patients, daily oral supplementation of 1000 mg of Ca (Ca carbonate) and 400 I.U. of vitamin D for 24 months will result in at least a 10% greater increase in total body bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA) compared to treatment with placebo and 400 I.U. vitamin D and this increased BMD will persist for at least 18 months after cessation of the trial. In addition, this project will determine the effect of Ca supplementation on bone physiology by measuring by measuring serum and urinary bone related minerals (Ca, phosphorus), hormones (parathyroid and vitamin D's), bone formation markers (osteocalcin, skeletal alkaline phosphatase), and bone resorption markers (urinary Ca/creatinine and pyridinoline crosslinks). The effects of variants of the vitamin D receptor allele on bone physiology and response to Ca supplementation will also be determined. 185 of the proposed study population of 192 JRA patients meeting eligibility criteria have been enrolled in this prospective, randomized, double-blind, placebo-controlled, 24-month clinical trial (RCT). The participants will also be evaluated 6 and 18 months following the RCT for persistence of treatment effect. To assess effectiveness of randomization and ongoing equality of treatment groups, baseline anthropometrics, pubertal status, physical activity and trial medication compliance will be performed. The baseline characteristics of the treatment groups were compared after a statistician not involved in the study randomized 125. The treatment groups were similar in all demographic parameters except for age at time of enrollment. This statistician adjusted the enrollment for subsequent participants and has balanced the treatment groups for age at enrollment. In addition to standard pill counts, compliance will be assessed (qualitative and quantitative) by the use of microelectronic monitoring and recording of medication container opening. This compliance data will be utilized during the trial to improve patient compliance and in analysis as a covariate affecting outcome.
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