CALCIUM SUPPLEMENTATION FOR BONE MINERALIZATION IN JUVENILE ARTHRITIS

约40%的JRA患者在儿童期或青春期出现明显的全身性骨质减少。女性在青春期达到终身骨量峰值，在许多JRA患者中骨量下降。目前还没有针对JRA患者骨质减少的公认治疗方法和对照试验。对JRA患者的观察性研究表明，他们普遍存在膳食钙（Ca）和维生素D摄入量不理想、胃肠道钙吸收显著降低和骨形成率低的情况。在JRA患者中，每日口服补充1000毫克钙（碳酸钙）和400国际单位维生素D，持续24个月，与安慰剂和400国际单位维生素D治疗相比，双能x射线吸收仪（DXA）测量的全身骨密度（BMD）增加至少10%，并且这种增加的BMD将在试验结束后持续至少18个月。此外，本项目将通过测定血清和尿骨相关矿物质（钙、磷）、激素（甲状旁腺和维生素d）、骨形成标志物（尿钙/肌酐和吡啶多啉交联）来确定钙补充对骨生理的影响。维生素D受体等位基因变异对骨骼生理和钙补充反应的影响也将被确定。

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 serum and urinary bone related minerals (ca, phosphorus), hormones (parathyroid and vitamin Ds), bone formation markers (urinary Ca/creatininine and pyridonoline crosslinks). The effects of variants of the vitamin D receptor allele on bone physiology and response to Ca supplementation will also be determined.