A B S T R A C T

In the current investigation, the potential alleviating effects of tianeptine against bone loss induced in ovariectomized (OVX) rats was determined. Two weeks following a bilateral ovariectomy operation, tianeptine treatment (12.5 and 25 mg/kg/twice/d) was initiated and continued for twenty-eight consecutive days. Changes in serum and urinary bone turnover biomarkers and osteoclastogenesisinducing factors were estimated. The femoral bone mineral content was estimated using inductivelycoupled-plasma mass spectrometry. Morphometric alterations of distal femoral bones were observed in the cortical and trabecular structures using micro-CT. Finally, femur bones were assessed for histopathological changes. The lack of estrogen significantly increased the levels of bone turnover biomarkers and inflammatory mediators. Mineral concentrations in the femoral bones were reduced in the OVX group. Furthermore, the femoral bone micro-architecture determined using micro-CT and histopathology were significantly altered by estrogen deficiency. Tianeptine, particularly the higher dose, corrected the elevated levels of bone metabolic products and pro-inflammatory cytokines. Tianeptine also improved mineral concentrations in femoral bones and the disturbed morphometric and histopathological features in OVX rats. In conclusion, tianeptine alleviated the osteoporotic changes in OVX animals, which may be via inhibition of the hypothalamic–pituitary–adrenal axis stress and osteoclastogenesis-provoking factors, suggesting attenuation of bone matrix degradation and osteoclast stimulation.