Purpose of investigation: Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are bone turnover modulators expressed by osteoblasts. The aim of this study was to assess the relationship between the circulating OPG/RANKL system, age and bone mass, in fertile age and postmenopausal women. Methods: In this cross-sectional observational study on 48patients (fertile age, n = 22; postmenopause, n = 26), we investigated the correlation between serum OPG and RANKL, age and bone mineral density (BMD). Serum concentrations of OPG and RANKL were determined by enzyme-linked immunosorbent assay(ELISA); estimate BMD evaluation was performed with heel quantitative ulrasonometry (QUS). Results: Serum OPG significantly increased (p=0.003) and serum RANKL significantly decreased (p = 0.002), in the postmenopausal group compared to fertile agewomen. A significant correlation of serum OPG with age (r_s = 0.39, p = 0.047) and BMD (r_s = 0.45, p =0.023) in postmenopausalwomen, and between RANKL and BMD (r_s = 0.48, p = 0.024) in fertile age was found. Conclusion: These data demonstrate in vivo that the OPG/RANKL system is significantly associated with menopausal status and could play a role in postmenopausal osteoporosis.