Osteoporosis, a debilitating condition which affects almost 20 million people in the U.S. alone, is characterized by a loss of bone tissue to the extent of structural failure. We propose that a functional level of bone mass is only attained and maintained as a result of a mechanically engendered osteogenic stimulus countering a net systemic drive towards resorption. If the functional stimulus is removed or weakened (as in disuse osteoporosis), or if the systemic stimulus is strengthened (as in calcium deficiency or post-menopausal osteoporosis), bone mass will decline, progressively increasing the individual's susceptibility to fracture. We wish to investigate the extent to which a bone suffering from disuse osteoporosis can be restored to its """"""""normal"""""""" mass by """"""""appropriate"""""""" mechanical stimuli. The objective of this three-year study is to compare the potential of two types of load bearing (dynamic or static) to inhibit and/or reverse the advancement of osteoporosis. The functionally isolated turkey ulna preparation will be developed as a model for disuse osteoporosis. In previous work using this model, we have observed a 15 to 20 percent loss of bone mass following only eight weeks of functional deprivation. In the proposed series of experiments, we intend to follow this initial period of disuse with an additional eight week period of mechanical stimulation. During this latter loading period: a) one series of animals will be subjected to a constant, static load regime; b) a second series will be subjected to a short daily period of an intermittent (dynamic) load regime; and c) a final series will be subjected to uninterrupted disuse for the entire sixteen weeks. The course, progress and balance of the remodeling response to these three parameters will be assessed from post-mortem histology, microradiography, and the distribution of fluorescent labels given over the experimental period. The clinical relevance of this study is targetted towards the prevention and/or reversal of bone loss in the immobilized patient and the aging post-menopausal population. Our preliminary results are encouraging since they demonstrate that bone loss may be prevented by extremely short periods of dynamic load bearing. These experiments will establish the potential of load bearing to restore bone mass in bones already osteoporotic.
