Detailed quantitative histologic studies of trabecular bone in slowly-growing ovariectomized rats are planned. Osteopenia and histologic indices of bone turnover will be characterized as a function of time postovariectomy. The effect of endocrine and pharmacologic agents that suppress bone turnover on the development of osteopenia in ovariectomized rats will also be evaluated. The knowledge derived from these studies could lead to testing of rational concepts of therapy in primates to minimize osteopenia following loss of ovarian function. Prevention of postmenopausal bone loss would alleviate orthopedic problems by reducing the incidence of vertebral, wrist, and hip fractures in the elderly female population. Trabecular bone of the proximal tibial metaphysis and lumbar vertebral body will be studied by standard bone histomorphometric techniques. The first experiment will characterize changes in trabecular bone mass and histologic indices of bone turnover in ovariectomized rats from 2-78 weeks postovariectomy. Terminal serum calcium, phosphorus, and estradiol will also be measured. The second experiment will evaluate the same parameters in ovariectomized rats treated daily with estrogen (17B-estradiol) or intermittently with ethane-1-hydroxy-1, 1-diphosphonate (EHDP) for 10, 26, or 52 weeks. It is hypothesized that bone loss in ovariectomized rats is exponential and is associated with increased bone turnover. It is further hypothesized that estrogen replacement slows bone turnover and thereby diminishes the rate of bone loss after ovariectomy. The final hypothesis is that suppression of bone turnover by EHDP will coincidentally diminish the rate of bone loss in ovariectomized rats. Validation of these hypotheses, if confirmed in experimental animals or human volunteers with adult bone remodeling, may provide a rationale for non-estrogenic treatment in the prevention of postmenopausal bone loss. Such a finding would benefit numerous postmenopausal women whose medical histories contain contraindications for estrogen therapy.
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