Osteogenic effectiveness of exercise loads and timing

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(a pilot study)
Osteoporosis increases bone fragility, contributes in the United States to 1.5 million bone breaks and over 17 billion dollars in health care costs per year and to reduced quality of life. It is imperative to develop therapies that increase bone strength and build bone in areas where the mechanical stresses are the highest particularly in older individuals in whom osteogenesis is reduced. Only physical activity and several hormones including the parathyroid hormone (PTH) secreted intermittently, growth hormone (GH) insulin-like growth factor-I (IGF-I) and estradiol (E2), were found capable of such site-specific strengthening of bones. Therapeutic approaches with bisphosphonates have only antiresorptive action and reduce fracture risk by only 40 to 60% ; with fluoride allow bone deposition in inappropriate locations, and with E2 have other undesirable side effects. The problems with the use of exercise and bone anabolic hormones in the prevention or treatment of osteoporosis are that the parameters of mechanical loading effective for increased bone formation, including the necessity for dynamic loading, suprathreshold stresses, and rapid mechanoreceptor desensitization, were (1) developed in animal models where loading was confined to a segment of the skeleton rather than elicited by exercise where dynamic loading is accompanied by increased secretion of PTH, GH and IGF-I; and (2) have to date not been translated to humans. Therefore the global hypothesis of this proposal is that the best approach to site-specific strengthening of bones in osteopenic postmenopausal individuals is to use dynamic exercise of the intensity, duration, and timing that most effectively increases secretion of PTH, GH, and IGF-I. Our specific aims are to determine (1) effective mechanical loading (2) shortest effective exercise duration; and (3) effective temporal distribution of exercise to elicit increases in plasma concentration of PTH, GH, and IGF-I and in markers of bone formation osteocalcin (OS), osteoprotegerin (OPG), carboxyterminal propeptide of type I procollagen (PICP) and bone-specific alkaline phosphatase (ALKP);. Measurements of markers of bone resorption, immunoactive carboxyterminal telopeptide of type I collagen (ICTP) in plasma and urinary N-telopeptide of type I collagen (NTX) will also be performed.

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