The changes in circulating osteoprotegerin after hormone therapy in postmenopausal women and their relationship with oestrogen responsiveness on bone

Abstract

Oestrogen replacement reduces the increased rate of bone remodelling after the menopause. Osteoprotegerin (OPG) is a negative regulator of osteoclast-mediated bone resorption. In vitro studies have shown that oestrogen stimulates OPG production. However, the role of OPG in physiological bone remodelling and its regulation by oestrogen in vivo remain controversial. In this study, we analysed the association between changes in serum OPG levels and bone turnover status before and after hormone therapy (HT) in healthy postmenopausal women. Ninety-nine healthy postmenopausal women of Korean ethnicity, aged 42-64 years (52.3 +/- 4.9 years, mean +/- SD) were enrolled in our study. Serum OPG levels were assessed by a highly sensitive sandwich-type enzyme immunoassay. Serum concentrations of osteocalcin (OC) and carboxyterminal telopeptides (CTx) were determined by electrochemiluminescence immunoassays. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry (DEXA). Baseline levels of OPG correlated neither a the bone formation marker, serum OC, nor with a bone resorption marker, serum CTx. No significant association of baseline OPG was found with baseline BMD measured at the lumbar spine and femoral neck. Serum OPG levels measured after 3 months and 1 year of HT decreased significantly compared to baseline (P < 0.001 in both). The changes in circulating OPG at 3 months of HT correlated with the changes in both serum OC (r = 0.226, P = 0.029) and serum CTx (r = 0.214, P = 0.038) at 3 months after HT. However, there was no significant association between the changes in circulating OPG after 3 months of HT and BMD values of the lumbar spine or femoral neck after 1 year of HT. Our results suggest that baseline OPG levels do not reflect bone turnover status and that serial measurements of serum OPG after HT are not a useful predictor of the long-term effects of oestrogen on bone density. The decrease in serum concentrations of OPG after HT may occur to compensate for the action of oestrogen in suppressing bone resorption.