The Effects of Obesity on Bone Structure and Strength

High body weight is protective against hip and spine fracture, but has been found to increase the risk of humerus, foot and ankle fracture. Increasing understanding of the actions of adipokines on bone suggests that there may be complex effects on different aspects of bone geometry and microarchitecture and that these effects may vary depending on whether adipokines act directly on bone cells or through the central nervous system and between cortical and trabecular compartments. Previous research is limited by the use of areal dual-energy x-ray absorptiometry (DXA) scans which may be inaccurate in obese populations due to increased body thickness. The aim of this study is to investigate the effect of obesity on bone mineral density, bone geometry, bone microarchitecture and bone strength of the hip, lumbar spine, distal radius and tibia. This is an observational, cross-sectional study of normal weight and obese individuals matched by age, gender, height, postcode and smoking. The total number of subjects will be 240; men and premenopausal women ages 25 to 40 years and men and postmenopausal women ages 55 to 75 years. DXA, high-resolution peripheral computed tomography (HR-pQCT), quantitative computed tomography (QCT) and finite element analysis will be used to assess bone structure and strength. Biochemical markers of bone turnover and hormones related to bone metabolism will also be measured in order to identify potential mediators of the effects of obesity on bone structure and strength. A sub-study has been included to evaluate the interaction of fracture risk and cardiovascular risk in obese and non-obese individuals. There is evidence of an interaction between bone mineral density (BMD) and cardiovascular risk and test the hypothesis that there are common pathways linking BMD and cardiovascular risk, including fat secretion of inflammatory cytokines e.g. interleukin-1 and adipokines e.g. leptin and adiponectin. Ultrasound based assessments of vascular function will be used to assess cardiac risk and relate these measures to bone density. Obese individuals have lower circulating levels of 25OHD. This may be due to poor nutritional intake, reduced sunlight exposure or the vitamin D being stored in fat tissue. The investigators will measure levels of 25OHD in lean, overweight and obese men and women to examine whether 25(OH)D is related to age or gender and whether low 25OHD in obesity affects bone health in subsets of lean, overweight and obese participants of different ages.