Osteoporosis has become a major health problem as the life expectancy of the general population has risen rapidly in recent years. Post-menopausal women are at greater risk because of accelerated bone loss induced by estrogen deficiency superimposed on age related bone loss. One of the important etiological factors in postmenopausal osteoporosis is the interaction between estrogen and PTH. PTH is known to be an important initiator of bone remodeling and persistent elevation of PTH, such as in hyperparathyroidism, presents as a risk factor for the development of osteoporosis. However, intermittent administration of PTH has been shown to be a promising regimen for improve bone mass in both the animals and humans. The dichotomy of this issue is not fully understood, especially in the estrogen deficient population. This project attempts to understand further the dualistic role of PTH as a catabolic and anabolic hormone in animal models of estrogen deficiency. The proposed study will have the following specific aims.
Specific Aim 1. To differentiate the anabolic action of continuous elevation of PTH from its catabolic action.
Specific Aim 2. To demonstrate the interactions of dietary calcium intakes with continuous and intermittent PTH administration under estrogen deficiency state, and Specific Aim 3. To study the interactions of PTH, cytokines and anti-resorptive agents at both tissue and subcellular levels in a mouse model of estrogen deficiency.
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