Effect of 16 months of treatment with tibolone on bone mass, turnover, andbiomechanical quality in mature ovariectomized rats

Tibolone (Org OD14) is a tissue-specific steroid with estrogenic effects on the bone and vagina but not endometrium. or breast and has been shown to p revent ovariectomy-induced bone loss in young and old rats. We evaluated th e effect of long-term tibolone treatment on bone parameters in mature ovari ectomized (OVX) rats. Six-month-old rats were allotted to one of six groups (n = 8). Sham-operated and control OVX groups received vehicle, whereas ot her groups (all OVX) received tibolone (125, 250, or 500 mug/day orally) or 17 alpha -ethinylestradiol (EE; 24 mug/day orally) for 16 months. Treatmen t with tibolone prevented ovariectomy-induced bone loss in peripheral (femu r and tibia) and axial (L1-L2 and L4) skeleton. In peripheral skeleton, tib olone and EF prevented loss of bone mass and quality to a similar extent. T ibolone dose-dependently inhibited trabecular bone volume loss in L1-L2 and tibia, and at 500 mug/day it inhibited 88% of L1-L2 and 55% of tibial volu me loss (p less than or equal to 0.05 in each case). Tibolone, 500 mug, res ulted in 10% greater cortical strength of femur (p less than or equal to 0. 05) and 60% greater compressive strength of L4 (p less than or equal to0.05 ) compared with vehicle-treated OVX rats. Tibolone and EE inhibited bone re sorption and turnover, assessed by urinary deoxypyridinoline/ creatinine an d plasma osteocalcin, respectively. We conclude that 16 months of tibolone treatment prevents ovariectomy-induced deterioration of axial and periphera l skeleton and preserves cortical and trabecular bone strength by reducing bone resorption.