Osteoporosis is a widespread condition associated with over 250,000 hip fractures each year. Although more than 90% of these fractures occur in individuals over 70, little information is available on the effectiveness, benefits and side effects of therapy for osteoporosis of the hip in elderly women. We postulate that in women age 65 and over: (1) a) bisphosphonate therapy will maintain femoral bone mass, b) estrogen replacement therapy will independently aid in maintaining hip bone mineral density, and c) the combination of bisphosphonate and estrogen replacement therapy will have an additional positive effect in maintaining femoral bone mass; and (2) bisphosphonate will have the unique complementary benefit of increasing femoral and radial bone strength estimates. To investigate these hypotheses, we will conduct a four-arm, double-blind, placebo-controlled study in community-dwelling elderly women age 65 years and over. Initially, all participants will complete a two month """"""""run in"""""""" phase of daily oral combined continuous estrogen-progesterone therapy to optimize compliance and reduce drop-out following subsequent randomization. Following this """"""""run in"""""""" period, 368 women will be randomized to receive daily oral therapy with (1) bisphosphonate therapy (Alendronate 10 mg), (2) standard combined continuous estrogen-progesterone replacement therapy (Premarin 0.625 g and Provera 2.5 mg), (3) standard combined continuous estrogen-progesterone replacement therapy (Premarin .625 mg and Provera 2.5 mg) and bisphosphonate (Alendronate 10 mg), or (4) placebo. The major outcome variable ill be hip bone mineral density as assessed by Dual Energy X-Ray Absorptiometry. We will follow bone density of the femoral neck, total hip, trochanter, intertrochanter, and Ward's triangle in addition to vertebral, radial and total bone density and indices of bone metabolism at six month intervals for two years. We will estimate femoral and radial bone strength as predicted by integrated measures of density and cross- sectional moments of inertia. We will investigate whether such therapy (1) will prevent or reverse femoral bone loss, (2) will maintain or increase bone strength estimates, (3) has differential effects on hip, vertebral, or radial bone mass, (4) has differential effects on cortical and trabecular bone density, and (5) alters indices of bone mineral metabolism. Furthermore, we will determine if the response to therapy can be predicted by indices of bone mineral metabolism or vitamin D receptor alleles. Data derived from this study should provide the basic for an effective intervention to stabilize or increase femoral bone mass and reserve architectural integrity in elderly women.
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