Renal osteodystrophy (ROD) is an early and universal disorder of bone metabolism in chronic renal insufficiency (CRI). As CRI progresses, abnormal bone metabolism results in sclerosis of trabecular bone, thinning of cortical bone and increased cortical porosity. Despite widespread ROD therapies, fracture rates on dialysis are markedly increased. CRI also results in gonadal dysfunction. Estrogen deficiency and ROD have similar detrimental effects on cortical bone loss, but opposing effects on trabecular bone. Unlike traditional densitometric measures of bone mass, peripheral quantitative computed tomography (pQCT) permits discrete assessment of trabecular and cortical bone density and dimensions, and bone strength can be reliably estimated. PQCT is an ideal tool to study the skeletal effects of CRI. The NIDDK recently established the Chronic Renal Insufficiency Cohort (CRIC) study to determine risk factors for CRI progression and cardiovascular disease in mild to severe CRI. This prospective cohort, ages 21-74 years, will undergo annual visits, providing an unparalleled opportunity to determine the effects of CRI on bone structure. The hypotheses of this ancillary bone study are that (a) cortical bone volume and density are significantly decreased in CRI, resulting in early and substantial reductions in bone strength, and (b) the progression of cortical and trabecular bone loss is associated with renal dysfunction, hyperparathyroidism, sex hormone deficiencies, decreased muscle strength, comorbidities, and concurrent medications. In healthy adults, bone structure and density undergo gender-specific changes with aging; therefore, this study requires a control group of similar age and gender. This prospective cohort study of bone structure in CRIC participants at the UPENN site will employ dual energy x-ray absorptiometry (DXA) and pQCT to assess bone dimensions, density and strength. The study will examine the effects of renal disease severity, hypogonadism, muscle strength, hyperparathyroidism, comorbid conditions and medications. The protocol will characterize sex hormone deficiencies in this cohort, determine the prevalence and incidence of vertebral fracture, examine baseline measures of bone turnover and regulators of osteoclastogenesis as predictors of bone loss, and will examine the utility of routine DXA in the assessment of ROD. Accurate characterization of bone structure in CRI is necessary to identify risk factors for fragility, and to evaluate potential therapies.
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