Relationships among serum receptor of nuclear factor-κB ligand, osteoprotegerin, high-sensitivity C-reactive protein, and bone mineral density in postmenopausal women: osteoimmunity versus osteoinflammatory

Objective: The aim of this study was to investigate the correlations among circulating osteoprotegerin (OPG), the receptor activator of nuclear factor-kappa B ligand (RANKL), high-sensitivity C-reactive protein (hsCRP), and bone mineral density (BMD) in healthy postmenopausal women. Methods: In a population-based study, highly specific enzyme-linked immunosorbent assay methods were used to evaluate the sera of 382 healthy Iranian postmenopausal women (mean age +/- SD, 58.7 +/- 7.5 y) for RANKL, OPG, hsCRP, degradation products of C-terminal telopeptides of type I collagen, and osteocalcin. BMD was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray absorptiometry. Results: Circulating levels of OPG (r = 0.30, P < 0.001) and the RANKL/CPG ratio (r = -0.17, P < 0.001) were significantly associated with age. The geometric mean of hsCRP was 1.89 mg/L (SE, 1.05) in the population studied. There was a significant correlation between log(hsCRP) levels and body mass index (BMI; r = 0.36, P < 0.001). Multivariate linear analyses revealed that age (beta = -0.295, P < 0.001), BMI (beta = 0.464, P < 0.001), RANKL (beta = -0.105, P = 0.014), and OPG (beta = 0.098, P = 0.029) were the independent determinants for lumbar BMD (R-2 = 0.35). Age (beta = -0.250, P < 0.001), BMI (beta = 0.486, P < 0.001), and RANKL (beta = -0.110, P = 0.009) were independently correlated with femoral neck BMN (R-2 = 0.36). Age- and BMI-adjusted analysis by quartiles of log-transformed hsCRP did not reveal an association with BMD, serum levels of biochemical markers of bone turnover, RANKL, or OPG. Conclusions: The circulating levels of the RANKL/CPG osteoimmunity system have an association with BMD, but subclinical systemic inflammation may not be involved in bone mass in healthy postmenopausal women.