The candidate is a pediatric nephrology fellow with advanced training in clinical epidemiology and a long-standing interest in clinical research. This application proposes a comprehensive, interdisciplinary program that will provide the candidate with the skills and experience necessary for her development into an independent investigator in pediatric renal epidemiology. The training component of this program includes a preceptorship with Dr. Brian Strom, Director of the Center for Clinical Epidemiology and Biostatistics, and completion of the formal course work and dissertation leading to a Ph.D. degree in Epidemiology. The research component proposes a study of bone disease among children with nephrotic syndrom (NS), the most common chronic renal disease of childhood. This study will examine the determinants of bone disease using the tools of clinical epidemiology in conjunction with state-of-the-art methods of laboratory evaluation of bone mineralization. The growing skeleton may be particularly vulnerable to the inhibitory effects of glucocorticoids on one formation. The clinical significance of decreased bone mineralization in children has not been addressed, either in terms of decrements in peak adult bone mass or tendency to fracture. Most children with NS require prolonged treatment with high-dose glucocorticoids. The primary hypotheses of this study are that children with NS and normal renal fuction will have decreased bone mineralization; the pattern of glucocorticoid therapy will affect the degree of osteopenia; and peak adult bone mass will be decreased. A cross sectional study will assess bone mineralization with dual dual energy x-ray absorptiometry in 200 children with a history of NS and 200 healthy controls. The candidate's pilot data demonstrates the study is feasible and suggests bone mineralization is decreased in children with NS. Glucocorticoid exposure will be quantitated and correlated with bone mineralization. A multivariate analysis will explore for effect modification and adjust for possible confounding effects of impaired growth and sexual maturation, calcium intake, vitamin D status, physical activity, and cyclosporin therapy. A fracture questionnaire will determine the fracture incidence which will be compared with fracture incidence reference data. A repeat bone mineralization measure will be obtained 6 months later in the NS subjects in order to explore the relationships among changes in bone mineralization, concurrent steroid exposure, and biomarkers of bone turnover. The study will identify patients at risk for clinically significant osteopenia. If the results demonstrate that bone mineralization does not recover or the fracture incidence is increased a clinical trial of therapy for optimizing bone mass among children with NS may be indicated.
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