Cortical and trabecular bone changes associated with tibolone in postmenopausal women: A randomized, open-label study compared with estrogen therapy and placebo.

BACKGROUND: Postmenopausal bone loss affects both cortical and trabecular compartments, with oxidative stress implicated in its pathogenesis. Tibolone is a tissue-selective hormone therapy with potential skeletal and antioxidative effects, but its structural impact compared to estrogen is understudied. This study evaluated the effects of tibolone on cortical and trabecular bone parameters in postmenopausal women, compared with estrogen therapy and placebo, using three-dimensional dual-energy X-ray absorptiometry (3D-DXA). METHODS: This 12-month, randomized, open-label trial included postmenopausal women aged 45-59 years, assigned to one of three groups: tibolone (2.5 mg/day), conjugated estrogens (0.625 mg/day) plus medroxyprogesterone acetate, or placebo. Bone parameters were measured at baseline, 6, and 12 months using 3D-SHAPER software. Oxidative stress markers were assessed concurrently. Longitudinal changes were analyzed using mixed-design (two-way repeated-measures) ANOVA. RESULTS: Of 92 randomized participants, 71 completed the study (tibolone n=22, estrogen n=27, placebo n=22). Changes in areal BMD did not exceed the least significant change of DXA measurements. Numerical increases in trabecular volumetric BMD and cortical thickness were observed in the tibolone group over 12 months, whereas numerical declines were noted in the placebo group and variable changes in the estrogen group; however, no statistically significant between-group differences were detected. Lipid peroxidation decreased in the tibolone and estrogen groups, while other oxidative stress markers remained largely unchanged. Adverse events were mild, with no statistically significant differences across groups. CONCLUSION: In this exploratory randomized study, no statistically significant between-group differences in cortical or trabecular bone parameters were detected over 12 months, and the observed changes in areal BMD did not exceed the least significant change of conventional DXA measurements. Therefore, the present study cannot establish clinically meaningful skeletal changes with tibolone. The numerical patterns observed with 3D-DXA should be considered hypothesis-generating and require confirmation in larger, adequately powered, and longer-term studies.