Osteoprotegerin, RANKL and bone turnover in postmenopausal osteoporosis

Background Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) play a critical role in the regulation of bone turnover, but the relative importance of these two cytokines in the pathogenesis of postmenopausal osteoporosis is controversial. Aim To investigate the relationship between circulating levels of OPG, RANKL, bone turnover and bone mineral density (BMD) in postmenopausal women. Methods A cross-sectional study of 185 women with osteoporosis and 185 age-and sex-matched control subjects was undertaken. Measurements were made of plasma OPG, RANKL, interleukin-6 (IL-6), sex steroids, calciotropic hormones, biochemical markers of bone turnover, BMD and anthropometry. Health questionnaires were administered. Results Plasma RANKL was significantly higher (p<0.0001) in women with osteoporosis (0.66 +/- 0.67 pmol/l) than in control subjects (0.37 +/- 0.38 pmol/l), as was plasma OPG (18.70 +/- 9.70 pmol/l in women with osteoporosis, 10.44 +/- 5.85 pmol/l in control subjects; p<0.0001). OPG/RANKL ratio was higher in women with osteoporosis (51.3) than in control subjects (36.6). The women with osteoporosis also had significantly higher biochemical markers of bone turnover, IL-6 and parathyroid hormone and lower 25-hydroxyvitamin D and oestradiol than the control subjects. Multiple regression analysis showed that lumbar spine and femoral neck BMD in postmenopausal women were best predicted by OPG and RANKL, giving an R-2 value of 15.5% and 14.9%, respectively. Conclusions This study indicates that the circulating levels of OPG and RANKL are inversely related to BMD and contribute to the development of osteoporosis in postmenopausal women.