STRUCTURAL EFFECTS OF RENAL OSTEODYSTROPHY DURING GROWTH

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DESCRIPTION (provided by applicant): Renal osteodystrophy (ROD) is a multifactorial disorder of bone metabolism in renal disease, resulting in thinning of cortical bone. Despite the widespread use of treatments to decrease bone resorption, fracture rates in young adults on dialysis are 100-fold greater than in the general population. Skeletal development is characterized by marked expansion and accumulation of bone. The growing skeleton may be particularly vulnerable to the structural effects of ROD, resulting in irreversible deficits in skeletal architecture and peak bone mass. Unlike traditional densitometric measures of bone mass, peripheral quantitative computed tomography (pQCT) permits the discrete assessment of trabecular and cortical bone density and dimensions, and bone strength can be reliably estimated. Therefore, pQCT is an ideal tool to study the structural effects of ROD during growth. Accurate characterization of the structural bone deficits and the risk factors for poor skeletal development in pediatric renal disease have not been addressed and are the focus of this study. The hypotheses are (a) cortical dimensions and strength are impaired in children with renal failure, (b) the bone deficit is associated with delayed growth and development, and with the underlying renal disease and therapies, and (c) the recovery and reconstitution of bone structure following renal transplantation is modulated by skeletal maturation, immunosuppressive therapies, and allograft function. In healthy children, bone mass is highly correlated with growth and maturation; therefore, to understand the extent of bone deficits in children with renal disease, these analyses will require a contemporary control group of similar age, gender, and ethnicity. This study is a multi-center prospective cohort study of bone accretion (dimensions, density and strength) in children with mild-to-severe renal failure, in dialysis patients, and in renal transplant recipients, compared to healthy controls. The study will be conducted in the pediatric GCRC facilities of the Children's Hospital of Philadelphia and the Children's Hospital Medical Center of Cincinnati. These sites both have large clinical pediatric nephrology programs and have extensive experience in studies of bone mineralization in childhood. The protocol will examine the effects of renal disease severity, delayed bone age, faltering growth, decreased muscle strength, hyperparathyroidism, immunosuppression (glucocorticoids, cyclosporine, tacrolimus), and ROD therapies. The protocol will also examine baseline measures of bone turnover as predictors of bone mineral accretion during growth and will examine the utility of routine dual energy x-ray absorptiometry in the assessment of ROD in children. The accurate characterization of the structural effects of ROD is necessary in order to identify and evaluate appropriate therapies to optimize peak bone mass and decrease fracture risk in a population that will continue to require renal replacement therapies throughout adulthood.