The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

Abstract

Abstract : Current osteoporosis therapies are able to treat the symptoms of osteoporosis, however little progress has been made toward understanding and addressing the underlying mechanisms contributing to age-related bone loss, or the ability to adapt to mechanical loading (exercise). Degeneration in peripheral nerve function with age may be one of these mechanisms, as neuropeptides affect the function of osteoblasts and osteoclasts in vitro, and nerve deactivation causes bone loss in vivo. This research investigates mechanisms by which peripheral sensory nerves influence bone maintenance and mechanotransduction using capsaicin-injected mice as a model of decreased peripheral sensory nerve function. We hypothesize that decreased sensory nerve function will result in increased functional adaptation of bone. In Aim 1 we investigated the relationship between peripheral sensory nerve function and bone structure. We found that capsaicin treatment resulted in a small but statistically significant decrease in trabecular and cortical bone structure. In Aim 2 we will determine the bone adaptation response of capsaicin- and vehicle-treated mice to increased mechanical loading. We hypothesize that capsaicin-treated mice will have an increased bone adaptation response to mechanical loading. The proposed research will establish the role of peripheral sensory nerves in age-related decreases in bone s ability to adapt to exercise. These studies may lead to novel therapies aimed at preserving healthy bone turnover with age. This research will be the basis for future studies investigating the interaction of peripheral nerves and bone, and peripheral nerve function as a potential mechanism of age-related bone loss.