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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZDK1-GRB-4 (M1))
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Kusek, John W
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Children's Hospital of Philadelphia
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Leonard, Mary B; Shults, Justine; Long, Jin et al. (2016) Effect of Low-Magnitude Mechanical Stimuli on Bone Density and Structure in Pediatric Crohn's Disease: A Randomized Placebo-Controlled Trial. J Bone Miner Res 31:1177-88
Jemielita, T O; Leonard, M B; Baker, J et al. (2016) Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays. Osteoporos Int 27:617-26
Baker, Joshua F; Von Feldt, Joan Marie; Mostoufi-Moab, Sogol et al. (2015) Insulin-like Growth Factor 1 and Adiponectin and Associations with Muscle Deficits, Disease Characteristics, and Treatments in Rheumatoid Arthritis. J Rheumatol 42:2038-45
Lo Re 3rd, Vincent; Lynn, Kenneth; Stumm, Emily R et al. (2015) Structural Bone Deficits in HIV/HCV-Coinfected, HCV-Monoinfected, and HIV-Monoinfected Women. J Infect Dis 212:924-33
Lee, Dale Y; Wetzsteon, Rachel J; Zemel, Babette S et al. (2015) Muscle torque relative to cross-sectional area and the functional muscle-bone unit in children and adolescents with chronic disease. J Bone Miner Res 30:575-83
Avitabile, Catherine M; Leonard, Mary B; Brodsky, Jill L et al. (2015) Usefulness of insulin like growth factor 1 as a marker of heart failure in children and young adults after the Fontan palliation procedure. Am J Cardiol 115:816-20
Tsampalieros, A; Berkenstock, M K; Zemel, B S et al. (2014) Changes in trabecular bone density in incident pediatric Crohn's disease: a comparison of imaging methods. Osteoporos Int 25:1875-83
Baker, Joshua F; Davis, Matthew; Alexander, Ruben et al. (2013) Associations between body composition and bone density and structure in men and women across the adult age spectrum. Bone 53:34-41
Reese, Peter P; Cappola, Anne R; Shults, Justine et al. (2013) Physical performance and frailty in chronic kidney disease. Am J Nephrol 38:307-15
Prosnitz, Aaron R; Leonard, Mary B; Shults, Justine et al. (2013) Changes in vitamin D and parathyroid hormone metabolism in incident pediatric Crohn's disease. Inflamm Bowel Dis 19:45-53

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