Objective: The aim of this study to was to evaluate the effect of fibroblast growth factor-23 (FGF-23), osteoprotegerin (OPG), receptor activator nuclear kB ligand (RANKL), and vitamin D hormones on bone loss in patients with hyperprolactinemia due to pituitary prolactinoma.,Methods: We recruited 46 premenopausal female patients with prolactinoma and age and sex-matched healthy controls (Group 3, n = 20) for this cross-sectional study. Prolactinoma patients were divided into 2 groups as patients newly diagnosed (Group 1, n = 26) and those under cabergoline treatment (Group 2, n = 20). Anthropometric and metabolic variables; hormonal profiles; and osteocalcin, deoxypyridinoline (DOP), and bone mineral density measurements were performed for all participants. FGF-23, OPG, and RANKL levels were analyzed in all groups.,Results: FGF-23, OPG, calcium, phosphorus, and parathormone levels were similar between all groups despite significantly higher levels in the control group in terms of vitamin D and RANKL levels than in patients. Bone loss was found more in Group 2, particularly observed in Z scores of femur and spinal bone (P<.05). Correlation analysis revealed a negative correlation between FGF-23 and femur neck T score (r = -0.0433, P =.05) in patients with active prolactinoma. A positive correlation was also observed between parameters of DOP and OPG (r = 0.673, P =.02). In patients with remission there were a negative correlation between prolactin and luteinizing hormone (r = -600, P =.08). Additionally, a negative correlation was found between osteocalcin and osteoprotegerin in patients in remission (r = -0.73, P =.01).,Conclusion: Our data indicated that FGF-23 and OPG levels do not play a critical role on the development of bone decrease in patients with hyperprolactinemia. However, further prospective studies in larger numbers of participants should be designed to clarify this issue.