CALCIUM SUPPLEMENTATION FOR BONE MINERALIZATION IN JUVENILE ARTHRITIS

约40%的JRA患者在儿童或青春期出现严重的全身性骨质疏松。 达到终生峰值骨量发生在青春期的女性，并已被证明是在许多JRA患者下降。目前既没有公认的治疗方法，也没有针对JRA患者骨质减少的对照试验。 在JRA患者中的观察性研究记录了钙（Ca）和维生素D的次优膳食摄入的高患病率，显著降低胃肠道Ca吸收和低骨形成率。在JRA患者中，每日口服补充1000 mg Ca（碳酸钙）和400 I.U.与安慰剂和400 I.U.治疗相比，24个月的维生素D治疗将导致通过双能X射线吸收测定法（DXA）测量的全身骨矿物质密度（BMD）增加至少10%。维生素D和这种增加的BMD将在试验停止后持续至少18个月。 此外，本项目将通过测量血清和尿液中骨相关矿物质（钙、磷）、激素（甲状旁腺和维生素D）、骨形成标志物（骨钙素、骨骼碱性磷酸酶）和骨吸收标志物（尿钙/肌酐和吡啶啉交联）来确定钙补充剂对骨生理学的影响。 还将确定维生素D受体等位基因的变体对骨生理学和对钙补充的反应的影响。在192例符合合格标准的JRA患者的拟定研究人群中，有185例已入组这项前瞻性、随机、双盲、安慰剂对照、为期24个月的临床试验（RCT）。 还将在RCT后6个月和18个月评价受试者的治疗效果持续性。 为了评估随机化的有效性和治疗组的持续平等性，将进行基线人体测量、青春期状态、体力活动和试验药物依从性。 在未参与研究的统计学家随机分配125名患者后，比较治疗组的基线特征。除入组时的年龄外，治疗组的所有人口统计学参数均相似。 该统计学家调整了后续受试者的入组，并根据入组时的年龄平衡了治疗组。 除了标准药丸计数外，还将通过使用微电子监测和记录药物容器打开情况来评估依从性（定性和定量）。 该依从性数据将在试验期间用于改善患者依从性，并作为影响结局的协变量用于分析。

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.