LUPUS ATHEROSCLEROSIS PREVENTION STUDY (LAPS) SUPPLEMENT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。狼疮联盟（关节炎基金会的一部分）资助了狼疮动脉粥样硬化预防研究（LAPS）[见附录F]，这是一项前瞻性，随机双盲安慰剂对照试验，阿托伐他汀与安慰剂，有两个结果：1)预防动脉粥样硬化（通过基线和2年螺旋CT冠状动脉钙化测量确定）和2)评估他汀类药物对SLE的免疫调节作用（通过每季度评估疾病活动度测量确定）。该试验提供了评估另一个结果的机会，他汀类药物对皮质类固醇诱导的骨质疏松症的影响。超过90%的SLE患者将接受慢性强的松治疗；骨质疏松性骨折是SLE中最常见的肌肉骨骼系统损伤。在以往的纵向研究中，我们发现70%的SLE患者存在骨质疏松，强的松是主要的危险因素。来自其他研究的数据强烈表明，阿托伐他汀对骨质疏松症有有益作用，可能是通过对BMP-2启动子的作用介导的。在这个申请中，我们要求临床研究中心为参加LAPS试验的200名参与者的基线和一年DEXA扫描提供资金。假设：由于阿托伐他汀组骨质疏松的改善或预防，或安慰剂组骨质疏松的进展，一年后阿托伐他汀组和安慰剂组的骨密度将有1.9%或更大的差异。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Alliance for Lupus (part of the Arthritis Foundation) has funded the Lupus Atherosclerosis Prevention Study (LAPS) [See Appendix F], a prospective, randomized double-blind placebo-controlled trial of atorvastatin vs. placebo, with two outcomes: 1) prevention of atherosclerosis (determined by baseline and 2-year measures of coronary calcification by helical CT) and 2) assessment of the immunomodulatory effects of statins on SLE (determined by assessment of disease activity measure on a quarterly basis). This trial affords the opportunity to assess another outcome, the effect of statins on corticosteroid-induced osteoporosis. Over 90% of the SLE patients participating will be on chronic prednisone; osteoporotic fractures are the most common musculoskeletal system damaged in SLE. In past longitudinal studies, we have found that 70% of SLE patients have osteoporosis and that prednisone is the major risk factor. Data from other investigation strongly suggests that atorvastatin has a beneficial effect on osteoporosis, likely mediated by an effect on the BMP-2 promotor. In this application, we are requesting that the Clinical Research center fund baseline and one-year DEXA scans in the 200 participants in the LAPS trial. SPECIFIC AIMS Hypothesis: There will be a 1.9% or greater difference between atorvastatin and placebo arms in bone mineral density at one year, due either to improvement in or prevention of osteoporosis in the Atorvastatin arm, or to progression in the placebo arm.