Renal osteodystrophy affects nearly an children with chronic renal failure, and growth retardation is a major clinical consequence; accordingly, recombinant human growth hormone (rhGH) has recently been used to enhance linear growth in pediatric patients with end-stage renal disease. Little is known, however, about the effects of rhGH therapy on bone formation and parathyroid gland function in children with renal osteodystrophy. Indeed, most studies have failed to consider whether the type of renal bone disease influences the response to rhGH in children or contributes to the suboptimal response in those undergoing regular dialysis. In the past, secondary hyperparathyroidism was the most common skeletal lesion of renal osteodystrophy in children, but a larger proportion of patients in recent years have histological and/or biochemical evidence of adynamic bone. This disorder is characterized by reduced rates of bone formation, normal or moderately elevated serum PTH levels, and no evidence of bone aluminum deposition. The impact of this disorder on linear growth in children is uncertain, and the role of rhGH as a modifier of PTH-dependent bone turnover in pediatric renal osteodystrophy is currently unknown. This current proposal will characterize the roles of rhGH and calcitriol as modifiers of bone formation and parathyroid gland function in children with selected types of renal bone disease; separate studies will be done for patients with low-turnover and high-turnover skeletal lesions. Bone formation will be evaluated by in cancellous bone by quantitative histomorphometry, and parathyroid gland function will be assessed by in vivo dynamic tests of PTH release. In addition, expression of mRNAs for collagen, alkaline phosphatase and PTH/PTHrP receptor will be determined by in situ hybridization in cancellous bone and in growth plate cartilage in bone biopsy samples from the iliac crest. These studies will provide new information about tissue specific modifiers of cancellous bone formation and endochondral bone formation in children with renal osteodystrophy.
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