Lasofoxifene (CP-336,156), a Selective Estrogen Receptor Modulator, Prevents Bone Loss Induced by Aging and Orchidectomy in the Adult Rat

It has been well documented that selective estrogen receptor modulators (SERMs) can prevent bone loss in ovariectomized rats and postmenopausal women. The purposes of this study were to determine the effects of a potent and orally active SERM, lasofoxifene (CP-336,156), on bone mass, bone strength, total serum cholesterol, prostate weight, and histology in adult male orchidectomized (ORX) rats. Sprague Dawley male rats at 10 months of age were divided into 6 groups, with 10 rats/group. The first group was necropsied on day 0 and served as basal controls. The remaining rats were either sham operated (n = 10) and treated orally with vehicle, or ORX (n = 40) and treated with either vehicle or lasofoxifene at 1, 10, or 100μ g/kg·day for 60 days. Total serum cholesterol, prostate weight and histology, distal femoral bone mineral density (DFBMD) by dual energy x-ray absorptiometry, and static and dynamic bone histomorphometry of the third lumbar vertebral body were determined. Maximal load and stiffness of the ...