Endocrine Abstracts

Raloxifene is a new selective estrogen modulator. It has been shown to prevent bone loss and to reduce vertebral fracture risk in postmenopausal women. This study was designed to investigate effects of raloxifene and oestradiol on bone formation and resorption in intact and ovariectomized (ovx) rat models. In the intact model, a total of 24 adult female rats were divided into three groups: Controls subcutaneously received saline alone. Raloxifene (2 mg/kg) and oestradiol (30 microgram/kg) were injected to two groups of animals for a period of six weeks at two daily intervals. In the second model, rats (n=24) were ovx and allowed to recover for a period of at least three weeks. Control group received vehicle alone. Remaining rats were divided into two groups and injected with raloxifene (2 mg/kg) and oestradiol (30 microgram/kg) for six weeks. Urine samples were collected from all animals 24 hours after the last drug administration. Urinary deoxypyridinoline (DPD, a bone absorption marker) was measured by ELISA. Serum alkaline phosphatase (ALP) and osteocalcin levels were determined by autoanalyzer and immunoradiometric method, respectively. Lumbar vertebrae (L2) of all animals were dissected out and processed for histopathological evaluation. Removal of ovaries significantly elevated urinary DPD levels (p<0.01) compared to intact controls. Treatment of both intact and ovx rats with oestradiol resulted in significant decreases (p<0.01) in DPD values. Raloxifene administration had no significant effect in the intact rats, but it remarkably reduced bone turnover in the ovx animals (p<0.001). Both oestradiol and raloxifene produced conflicting effects on serum ALP and osteocalcin levels in both animal models. Both oestradiol and raloxifene reduced the necrotic effects of ovariectomy on the histology of L2. These findings suggest that raloxifene exerts its protective effects by reducing bone resorption, similar to that of oestradiol, in ovx rats.