Excessive bone loss occurs following spinal cord injury (SCI) leading to osteoporosis and an increased risk of low-impact fracture in up to 50% of all individuals with neurologically complete SCI. These fractures can be catastrophic as they limit mobility, worsen disability, and predispose to medical complications While the underlying cause of this bone loss remains to be clarified, it is distinct in severity and pattern from other known causes of osteoporosis including disuse and postmenopausal osteoporosis. In contrast, the metaphyses of the distal femur and proximal tibia (i.e., above and below the knee) are the most commonly fractured sites following SCI. Currently, little is known about the cause of, the natural history, or the specific factors that contribute to the severity of bone loss following SCI. Based on preliminary studies, we hypothesize that visceral fat is involved in the pathogenesis of SCI-induced bone loss and may be a mediator of osteoporosis severity and fracture risk in this population. We propose to investigate the relationship between visceral fat, circulating levels of fat derived hormones, and longitudinal change in bone mineral density in chronic SCI. Participants with SCI whose health behaviors (smoking, alcohol use) and comorbid illnesses are known due to enrollment in a longitudinal health study at VA Boston will be studied. This study will be the first large longitudinal study of bone loss in chronic SCI, and is both significant and innovative because it will be the first to use SCI as a clinical model to characterize adipose mediated bone loss occurring in isolation from mechanical loading. Defining the rate of bone loss at the distal femur and proximal tibia and assessing relationships with visceral fat will have important implications for the management and prevention of osteoporosis in SCI. If confirmed, these findings will lay the groundwork for novel clinical programs that target excess body weight and to promote mechanical stimulation of bone to improve bone mass and prevent osteoporotic fractures. PUBLIC HEALTH RELEVANCE: This project seeks to understand bone loss triggered by spinal cord injury. Rapid, severe bone loss occurs after the spinal cord injury leaving the bones brittle and easy to fracture. This bone loss is not well understood. But, it appears to be different from bone loss seen with aging in that it affects the knees more than the hips and spine. We believe that injury severity and the amount of stored central (visceral) fat are important factors in determining how much bone is lost following spinal cord injury. We will test this hypothesis by determining the amount of bone lost in subjects with more severe injury, those with less severe injury, and those without injury. We will also determine if people with SCI and greater amounts of visceral fat lose more bone than those with SCI and less fat and assess relationships with bone loss and hormones in the blood that are related to fat.