Increased survival of children with SLE into adulthood has resulted in the emergence of morbidities not previously well studied. Effective evaluation of this morbidity requires longitudinal study designs with attention to disease severity at onset and timing of disease onset relative to growth and development. Thus, a primary goal is to develop a well characterized Northern California longitudinal pediatric and adolescent SLE cohort demonstrating diversity across age (minimum seven years), ethnicity, and gender with a corresponding longitudinal tissue bank. The cohort will serve as a resource for the future study of many aspects of long-term outcome in this population. The career development component of this application includes completion of the UCSF Master in Clinical Research degree program with a focus on learning methods designed to analyze repeated measurements, multiple variables, and molecular epidemiology, all important skills for analyzing longitudinal multi- system disease data-sets. The scientific component of this application addresses the development of osteoporosis in pediatric onset SLE. Coincident timing of disease onset and achievement of normal peak bone mass may result in an increased risk for future osteoporosis and fracture. Annual measurements of SLE-associated reductions of bone mineral density (BMD) assessed utilizing dual energy X-ray absorptiometry (DEXA) and single energy quantitative computed tomography (QCT) will be correlated with disease-, treatment- and host-related factors and corresponding markers of bone metabolism. The relationship between skeletal maturation assessed by bone age and longitudinal changes of BMD will be determined by evaluating the timing and level of peak bone mass, and the contribution of the timing of disease to reductions of BMD. The findings of this project may result in the development of bone age- specific treatment regimens for pediatric SLE, and ultimately will contribute to improving the quality of adult life for individuals with childhood-onset SLE. Furthermore, development of this well characterized SLE cohort will serve as an important future resource and builds a foundation for studying many lifelong effects of childhood-onset SLE.
