Overcoming these problems will require safe and effective countermeasures not only to prevent bone loss, but also to maintain the functional-mechanical integrity of the tissue during prolonged space flight. A necessary prerequisite for development of those countermeasures is the identification of appropriate cellular targets for both processes. Those cellular targets have not yet been fully characterized.
Osteoclasts are clearly the agents driving bone loss due to unloading.
Thus, they present an obvious countermeasure target for modulating bone loss in space flight and in other hypodynamic loading situations. Available pharmacological strategies to inhibit osteoclastic resorption have a high likelihood of success, though definitive long-term data for remodeling suppression after unloading do not exist. Changes in osteocyte integrity result from long-term loss of normal mechanical loading. If the normal remodeling response of bone to impaired osteocytes is suppressed, as would be the case with treatment using an anti-resorptive agent, then regions of osteocytes can die, leading to the accumulation of devitalized bone. To test these hypotheses, we will undertake a series of long-term immobilization experiments in a canine model, with biphosphonate treatment to prevent bone loss.