ABSTRACT
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.