Circulating osteoprotegerin in postmenopausal osteoporotic women: Marker of impaired glucose regulation or impaired bone metabolism

Objective: Osteoprotegerin (OPG) is closely related to insulin resistance and bone remodeling. However, no studies have examined the role of OPG in postmenopausal women with coexistent impaired glucose and bone regulation. The present study investigated the relationship of OPG to glucose homeostasis and insulin resistance in postmenopausal osteoporotic women with different types of glucose tolerance. Methods: In all, 114 postmenopausal osteoporotic women were divided into three groups according to glucose tolerance status: 51 with normal glucose tolerance (NGT, group 1), 31 with impaired glucose tolerance (IGT, group 2), and 32 with type 2 diabetes mellitus (DM, group 3). Study participants were evaluated for metabolic parameters, OPG, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and bone mineral density parameters. Results: The OPG levels differed significantly across groups and increased from group 1 to group 3 in a continuous fashion (analysis of variance, P<0.0001). In post-hoc analysis, OPG was significantly lower in osteoporotic women with NGT, than participants with IGT and DM (P<0.05 and P<0.0001, respectively). OPG was positively associated with HOMA-IR (P<0.0001). No association between serum OPG levels and measures of BMD was observed. In a multiple regression analysis, OPG emerged as an independent predictor of HOMA-IR even after controlling for age, body mass index, and creatinine. Conclusions: OPG is significantly higher in postmenopausal osteoporotic women with impaired glucose regulation (IGT and DM) than women with NGT. OPG was independently associated with insulin resistance assessed by HOMA-IR. Thus, measurement of OPG may potentially be considered as a prediabetic state screening in postmenopausal osteoporotic women.