BUILDING BONE IN OSTEOPOROSIS WITH PTH AND ESTROGEN

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At present, there are no drugs approved for the treatment of osteoporosis. While antiresorptive agents appear to be effective in preventing the disease, it is generally agreed that their ability to increase bone mass is modest at best. In order to be viable in the therapy of established osteoporosis, agents will need to have a strong anabolic effect. Studies in vivo in man and animals show that parathyroid hormone (PTH) administered in relatively low doses intermittently stimulates bone formation. This is in contrast to its well established ability to stimulate bone resorption when it is given in high doses continuously. The mechanisms of those paradoxical effects of PTH are poorly understood, but the results of recent studies in vitro suggest that the anabolic effects may be related to the ability of PTH to stimulate osteoblasts to produce insulin-like growth factor (IGF-I). Evidence has accumulated that estrogen acts directly to decrease osteoclastic bone resorption and may also have effects on the osteoblast that are essential to normal bone formation. It is well established that estrogen replacement therapy (ERT) prevents the accelerated bone loss that occurs in most women after the menopause. Furthermore, ERT, by definition, seeks only to restore normal estrogenic function, which when present aids in maintaining both bone and mineral balance. The purpose of the proposed investigation is to determine the efficacy of the combined administration of synthetic human parathyroid hormone fragment, 1-34, (HPTH 1-34) and estrogen- progesterone replacement in the treatment of postmenopausal women with osteoporosis. We hypothesize that such treatment will increase bone mass and effect a distribution of vertebral bone mineral that favors increased strength more than treatment with individual constituent agents alone. The osseous effects of combined PTH 1-34 - estrogen therapy will be monitored with conventional dual energy x-ray absorptiometry measurements of the spine, hip and forearm, as well as a new, experimental approach using three-dimensional quantitative computed tomography to assess vertebral bone mineral distribution. Other outcome measures will include serial measurement of bone markers including serum alkaline phosphatase and osteocalcin, and urine pyridinoline crosslinks.