title: Skeletal effects of bazedoxifene paired with conjugated estrogens in ovariectomized rats.
abstract: 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 0.3mg/kg, CE 2.5mg/kg, or combined BZA/CE (BZA 0.1, 0.3, or 1.0mg/kg with CE 2.5mg/kg) over 12months 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 1.0mg/kg/day with CE 2.5mg/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, 12months 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.
authors.affiliation: Pfizer Inc, 500 Arcola Rd, Collegeville, PA 19426, USA. Barry.Komm@pfizer.com
authors.forename: Barry S
authors.initials: BS
authors.lastname: Komm
authors.forename: Fay
authors.initials: F
authors.lastname: Vlasseros
authors.forename: Rana
authors.initials: R
authors.lastname: Samadfam
authors.forename: Luc
authors.initials: L
authors.lastname: Chouinard
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Smith
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D009929:Organ Size; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene