Abstract
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.
Highlights
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]
Serum OPG concentration was negatively correlated with lumbar spine (r = −0.123, P < 0.001), femoral neck (r = −0.351, P < 0.001), and total hip bone mineral density (BMD) (r = −0.287, P < 0.001) in total cohort
The negative correlations between serum OPG levels and BMDs of lumbar spine, femoral neck, and total hip are higher for women (r = −0.299, P < 0.001; r = −0.400, P < 0.001; r = −0.342, P < 0.001, respectively), and lower for men
Summary
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]. Recent studies showed that low BMD is a risk factor for fracture in patients with predialysis or dialysis CKDs [4,5,6]. A prospective, population-based Bruneck Study showed that OPG was an independent risk factor for the progression of atherosclerosis and for the onset of cardiovascular diseases [13]. A cross-sectional study showed that serum OPG levels were positively associated with a high coronary artery calcification score, and could be used as a marker for severe coronary artery calcification in predialysis patients with diabetes [14]
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