Association of Serum Osteoprotegerin Levels with Bone Loss in Chronic Kidney Disease: Insights from the KNOW-CKD Study

PLOS ONE, Dec 2019

Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density. This study examined the association between serum osteoprotegerin levels and bone loss in patients with chronic kidney disease, a condition associated with increased risk of mineral and bone disorders. The bone mineral densities of the lumbar spine, total hip, and femur neck were assessed by dual-energy X-ray absorptiometry; serum osteoprotegerin levels were measured at baseline for 1,423 patients enrolled in the prospective KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Patients aged ≥50 years and with a T-score ≤ –2.5 were diagnosed as having osteoporosis. Multivariable linear regression analysis indicated independent association between serum osteoprotegerin levels and decreased bone mineral density in the lumbar spine (B: –0.489, 95% confidence interval [CI]: –0.883 to –0.095, P = 0.015), and total hip (B: –0.349, 95% CI: –0.672 to –0.027, P = 0.027). However, bone mineral density of the femur neck was not associated with serum osteoprotegerin levels in women. After adjustments, no independent association was found between serum osteoprotegerin levels and bone mineral density in men. In multivariable logistic regression analysis, serum osteoprotegerin levels were associated with increased risk of osteoporosis in women (odds ratio [OR]: 4.72, 95% CI: 1.35 to 16.52, P = 0.015), but not in men (OR: 0.21; 95% CI: 0.04 to 1.31, P = 0.095). To summarize, in female patients with chronic kidney disease, increased serum osteoprotegerin levels were independently associated with decreased bone mineral density in the lumbar spine and total hip, and with increased risk of osteoporosis. Therefore, the measurement of serum osteoprotegerin concentration might be useful as a surrogate marker for determining bone loss in patients with chronic kidney disease, especially for women, although not so much for men.

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Association of Serum Osteoprotegerin Levels with Bone Loss in Chronic Kidney Disease: Insights from the KNOW-CKD Study

November Association of Serum Osteoprotegerin Levels with Bone Loss in Chronic Kidney Disease: Insights from the KNOW-CKD Study Chang Seong Kim 1 2 3 Eun Hui Bae 1 2 3 Seong Kwon Ma 1 2 3 Seung Hyeok Han 0 1 3 Kyu Hun Choi 0 1 3 Joongyub Lee 1 3 Dong Wan Chae 1 3 Kook-Hwan Oh 1 3 Curie Ahn 1 3 Soo Wan Kim 1 2 3 1 3 0 Depatment of Internal Medicine, Yonsei University College of Medicine , Seoul , Korea , 3 Medical Research Collaborating Center, Seoul National University Hospital and Seoul National University College of Medicine , Seoul , Korea , 4 Department of Internal Medicine, Seoul National University , Seoul , Korea 1 Funding: This research was supported by grants 2011E3300300, 2012E3301100 and 2013E3301600 from Research of Korea Centers for Disease Control and Prevention, by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2084), by Basic Science Research Program through the National 2 Department of Internal Medicine, Chonnam National University Medical School , Gwangju , Korea 3 Editor: Hideharu Abe, Tokushima University Graduate School , JAPAN Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density. This study examined the association between serum osteoprotegerin levels and bone loss in patients with chronic kidney disease, a condition associated with increased risk of mineral and bone disorders. The bone mineral densities of the lumbar spine, total hip, and femur neck were assessed by dual-energy X-ray absorptiometry; serum osteoprotegerin levels were measured at baseline for 1,423 patients enrolled in the prospective KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Patients aged 50 years and with a T-score ±2.5 were diagnosed as having osteoporosis. Multivariable linear regression analysis indicated independent association between serum osteoprotegerin levels and decreased bone mineral density in the lumbar spine (B: ±0.489, 95% confidence interval [CI]: ±0.883 to ±0.095, P = 0.015), and total hip (B: ±0.349, 95% CI: ±0.672 to ±0.027, P = 0.027). However, bone mineral density of the femur neck was not associated with serum osteoprotegerin levels in women. After adjustments, no independent association was found between serum osteoprotegerin levels and bone mineral density in men. In multivariable logistic regression analysis, serum osteoprotegerin levels were associated with increased risk of osteoporosis in women (odds ratio [OR]: 4.72, 95% CI: 1.35 to 16.52, P = 0.015), but not in men (OR: 0.21; 95% CI: 0.04 to 1.31, P = 0.095). To summarize, in female patients with chronic kidney disease, increased serum osteoprotegerin levels were independently associated with decreased bone mineral density in the lumbar spine and total hip, and with increased risk of osteoporosis. Therefore, the measurement of serum osteoprotegerin concentration might be useful as a surrogate marker for determining bone loss in patients with chronic kidney disease, especially for women, although not so much for men. - OPEN ACCESS Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (2016R1A2B4007870) and by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A01051769), Chonnam National University Hospital Institute for Biomedical Science (CRI14008-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Introduction Patients with mild to moderate chronic kidney disease (CKD), or end-stage renal disease have an increased risk for fracture because reduced kidney function is associated with bone loss [ 1, 2 ]. The Kidney Disease: Improving Global Outcomes guidelines suggest that bone mineral density (BMD) screening should not be performed routinely for CKD patients due to a lack of association between BMD and fractures in CKD patients with mineral bone disease [3]. However, recent studies showed that low BMD is a risk factor for fracture in patients with predialysis or dialysis CKDs [4±6]. Therefore, assessment of bone loss using BMD may provide information to help anticipate fractures in this high-risk population. Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor super family, and a decoy receptor for the receptor activator of nuclear factor-κB (RANK) ligand, which is predominantly expressed by osteoblasts and by the vascular endothelium. OPG plays a critical role in the regulation of bone turnover [ 7 ]. OPG specifically inhibits osteoclastic bone resorption and vascular calcification by interfering with binding of the RANK ligand to RANK, as well as promotes the surv (...truncated)


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Chang Seong Kim, Eun Hui Bae, Seong Kwon Ma, Seung Hyeok Han, Kyu Hun Choi, Joongyub Lee, Dong Wan Chae, Kook-Hwan Oh, Curie Ahn, Soo Wan Kim, Representatives of the KNOW-CKD Investigator Group. Association of Serum Osteoprotegerin Levels with Bone Loss in Chronic Kidney Disease: Insights from the KNOW-CKD Study, PLOS ONE, 2016, Volume 11, Issue 11, DOI: 10.1371/journal.pone.0166792