A 3-year study of prevention of postmenopausal bone loss: conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone.

The aim of this study was to investigate the effects of tibolone in the prevention of postmenopausal bone loss over 3 years, and to compare these with the effects of sequential hormone replacement therapy. Forty early postmenopausal women were randomized to a 21-day regimen of conjugated equine estrogens (CEE, Premarin) plus sequential medroxyprogesterone acetate (MPA, Prodafem), or tibolone (Livial) daily. In total, 36 women completed 12 months and were considered for the intent-to-treat analysis, 34 completed 24 months and 23 completed 36 months. Main drop-out reasons were: lost to follow-up (n = 9) and minor side-effects (n = 4). Bone mineral density was measured at baseline and after 6, 12, 24 and 36 months, using dual-energy X-ray absorptiometry at the lumbar spine and the upper femur (neck, trochanter, total hip). In both groups, bone loss was prevented. Treatment with tibolone demonstrated significant increases in bone density at the spine (+4.6%; p < 0.01), at the total hip (+3.2%; p < 0.01) and at the trochanter (+4.5%; p < 0.01), whereas the CEE/MPA group showed a non-significant increase of bone mineral density at the lumbar spine (+2.6%) but no increases at the hip. Between-group differences in bone mineral density changes were significant (p < 0.05) for the total hip and the trochanter at 36 months. This increase of bone mineral density was not accompanied by changes in insulin-like growth factor-I (IGF-I) or insulin-like growth factor binding protein-3 (IGFBP-3) in either group. Osteocalcin, alkaline phosphatase and urinary ratios of hydroxyproline/creatinine and calcium/creatinine significantly decreased in both groups. In conclusion, sequential CEE/MPA prevented cortical and trabecular bone loss, with a transient increase of bone mineral density only during the first 6 months. Tibolone not only prevented cortical and trabecular bone loss, but further increased bone mineral density at the lumbar spine and at the hip throughout the 3 years of treatment, suggesting a sustained positive effect on bone mass.