Skeletal effects of bazedoxifene paired with conjugated estrogens in ovariectomized rats

A novel approach to menopausal therapy is the tissue selective estrogen complex (TSEC) that partners bazedoxifene (BZA) with conjugated estrogens (CE). We examined the effects of daily treatment with BZA 0.3 mg/kg, CE 2.5 mg/kg, or combined BZA/CE (BZA 0.1, 0.3, or 1.0 mg/kg with CE 2.5 mg/kg) over 12 months on bone mass, bone architecture and strength, and biochemical markers of bone turnover in ovariectomized (OVX) female Sprague-Dawley rats vs OVX control rats. Total cholesterol and uterine weights were also evaluated. All BZA/CE dose combinations prevented ovariectomy-induced increases in bone turnover and significantly increased bone mineral density (BMD) at the lumbar spine, proximal femur, and tibia compared with OVX controls. All BZA/CE doses evaluated also prevented many of the ovariectomy-induced changes of the static and dynamic parameters of the cortical compartment of the tibia and the cancellous compartment of the L1 and L2 vertebrae. All BZA/CE doses increased biomechanical strength at the lumbar spine (L4) compared with OVX animals. The co-administration of BZA 0.3 and 1.0 mg/kg/day with CE 2.5 mg/kg/day showed a dose-dependent reduction in uterine wet weight compared with administration of CE alone. All BZA/CE doses significantly lowered total cholesterol levels compared with OVX controls. In conclusion, 12 months of treatment with BZA/CE in OVX rats effectively maintained BMD, bone microstructure, and bone quality; and the pairing of BZA with CE prevented CE-induced uterine stimulation.

Research highlights► A TSEC pairing BZA and CE was evaluated in OVX rats over 12 months. ► BZA/CE significantly increased BMD at the lumbar spine, proximal femur, and tibia. ► BZA/CE prevented many ovariectomy-induced changes in cortical and cancellous bone. ► BZA/CE increased biomechanical strength at the lumbar spine vs OVX controls. ► Co-administration of BZA and CE prevented CE-induced uterine stimulation.