中国高原地区老年男性退行性骨质疏松患者氧化应激相关因子和骨代谢指标的相关性:非随机对照临床试验方案

摘要

背景:低氧是影响和调节骨生长代谢的重要因素,因此高原低氧地区老年人骨质疏松患者较多.与氧化应激有关的低氧诱导因子可诱导血管内皮生长因子、胰岛素样生长因子及内皮素等多种因子表达异常,但是否能影响骨代谢指标的变化尚不清楚.目的:试验探讨高原地区老年男性退行性骨质疏松患者氧化应激相关因子和骨代谢指标的相关性.方法:试验为前瞻性,单中心,非随机,对照临床试验方案.试验计划纳入中国青海大学附属医院中国高原低氧地区老年退行性骨质疏松患者120例设为骨质疏松组,同时收集120位健康老年人作为对照组.于入院后1 d采用酶联免疫吸附法检测两组血清氧化应激相关因子低氧诱导因子1α,2α,血管内皮生长因子、骨钙素及抗酒石酸酸性磷酸酶5 b水平变化,采用双能X射线骨密度仪检测L1-4椎体、右侧股骨颈和股骨大转子共3个区域的骨密度变化.试验的主要观察指标为入院后1 d血清低氧诱导因子1α水平变化;次要观察指标为入院后1 d血清低氧诱导因子2α,血管内皮生长因子及骨钙素及抗酒石酸酸性磷酸酶5 b水平变化;入院后1 d氧化应激指标低氧诱导因子1α,2α,血管内皮生长因子和骨代谢指标骨钙素及抗酒石酸酸性磷酸酶5 b水平的相关性.试验经青海大学附属医院伦理委员会批准[审批单位:青海大学附属医院,审批号:QHY1402G].研究符合世界医学会制定的《赫尔辛基宣言》的要求.参与者本人对试验方案和过程均知情同意,并签署知情同意书.试验于2015年1月开始进行患者招募,样本及数据收集时间为2015年1月至2018年2月,结果指标分析时间及试验完成时间为2018年3月.文章结果将以科学会议报告,或在同行评议的期刊上发表传播.试验已在中国临床试验注册中心注册(注册号:ChiCTR-ROC-17012848).讨论:文章希望通过此试验证实高原地区老年男性退行性骨质疏松患者氧化应激相关因子和骨代谢指标具有相关性,以进一步明确高原地区老年男性退行性骨质疏松的发病危险因素,从而为该地区人群骨质疏松发生及发展的预防提供帮助.%BACKGROUND: Hypoxia is an important factor that affects bone formation and regulates bone growth. Therefore, many elderly patients living in high-altitude hypoxic areas exhibit osteoporosis. Oxidative stress-related hypoxia-inducible factors can induce abnormal expression of various factors including vascular endothelial growth factor (VEGF),insulin-like growth factor, and endothelin. However, it remains unclear whether these factors influence changes in bone metabolic markers.OBJECTIVE: To investigate the correlation between oxidative stress-related factors and bone metabolic markers in elderly male patients with degenerative osteoporosis who reside in the high-altitude hypoxic area of China.METHODS: This is a prospective, single-center, non-randomized, controlled trial. One hundred and twenty elderly male patients with degenerative osteoporosis residing in the high-altitude area of China who receive treatment at the Affiliated Hospital of Qinghai University of China are included as osteoporosis group; 120 healthy elderly males who concurrently receive physical examination are included as control group. One day after admission, serum levels of hypoxia-inducible factor 1-alpha (HIF-1α), HIF-2α, VEGF, osteocalcin, and tartrate-resistant acid phosphatase 5 b (TRACP 5 b) were measured using an enzyme-linked immunosorbent assay. Bone mineral density in L1-4 segments, right femoral neck, and the greater trochanter of the femur was detected using dual-energy X-ray absorptiometry. The primary outcome measure of this study is serum HIF-1α levels at 1 day after admission. Secondary outcome measures include serum levels of HIF-1α, HIF-2α, VEGF, osteocalcin, and TRACP 5 b at 1 day after admission, as well as the correlation between serum levels of oxidative stress indicators (HIF-1α, HIF-2α, and VEGF) and bone metabolic markers (osteocalcin and TRACP 5 b) at 1 day after admission. This study was approved by the Ethics Committee of the Affiliated Hospital of Qinghai University of China (approval No. QHY1402G). The study is performed in accordance with the Declaration of Helsinki.Participants are informed of the study protocol and procedures, and signed an informed consent. Participant recruitment,blood sampling, and data collection are performed during January 2015 to February 2018. Outcome measure analysis and trial completion will be in March 2018. Results will be disseminated through presentations at scientific meetings and/or by publication in peer-reviewed journals. This trial was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR-ROC-17012848).DISCUSSION: Findings from this study aim to validate the correlation between oxidative stress-related factors and bone metabolic markers in elderly male patients with degenerative osteoporosis who reside in the high-altitude area of China.We intend to confirm risk factors of degenerative osteoporosis in elderly males living in high-altitude hypoxic areas, thus providing guidance for preventing osteoporosis occurrence and development in high-altitude hypoxic areas of China.