The study was conducted on 40 women in the early postmenopausal period, aged 52.3±3.1 years with primary osteoporosis unmanageable in treatment, divided into 2 groups based on a randomized list. Group I (n-20) was administered orally fluoride 0.25 mg kg-1 24 h-1 with modified transdermal hormone therapy/HRT, and group II (n-20) was administered orally fluoride and supplement hormonal therapy (HST) in 21 therapeutic cycle. The serum concentrations of osteocalcin (OC), procollagen (PICP), insulin-like growth factor I (IGF-1), prolactin basic (PRL) and prolactin after metoclopramide (PRL/ MCP) 4 times by using radioimmunoassy methods, before treatment and after 1, 3, 12 months of treatment. Bone mineral density (BMD) L2 – L4 was determined before treatment and at 12 month with a dualenergy x-ray absorptiometry scanner (Lunar DPX-1Q). In group I women receiving fluoride and transdermal HRT IGF-1 increased significantly while the concentrations of OC and PICP significantly decreased after 3 and 12 months of treatment but no statistically significant changes in the PRL concentration occurred. In group II women receiving orally fluoride and HST, a significant decrease in the concentration of IGF-1, OC after 3 and 12 months and a significant increase in the concentration of PRL and PRL/ MCP after 1, 3 and 12 months of treatment compared with the baseline values appeared. The concentration of type I procolagen (PICP) showed no statistically significant changes. Increase in bone mineral density was statistically significant L1, L2 (p < 0.05), L3, L4 (p < 0.01) compared with the baseline in the group receiving transdermal HRT. In women receiving fluoride and orally HST increase in the bone mineral density for L1 and L2 was non-insignificant, whereas for L3 and L4 it was significantly higher compared with the baseline (p < 0.05).