Secondary hyperparathyroidism (2-HPT) remains the predominant lesion of renal osteodystrophy in pediatric patients treated with maintenance dialysis, despite daily calcitriol therapy. On the other hand, adynamic renal osteodystrophy often occurs after intermittent calcitriol therapy, and linear growth declines particularly in pre-pubertal children who develop adynamic bone after intermittent calcitriol. Both calcitriol and the use of calcium-containing phosphate binding agents have been implicated in the pathogenesis of adynamic bone. The relationship between PTH and bone formation rate is altered by intermittent calcitriol therapy. This change may reflect differences in the skeletal response to PTH in various types of renal osteodystrophy, but calcitriol-mediated increases in serum calcium levels may also contribute. Whether treatment of 2-HPT with other vitamin D sterols that lower parathyroid hormone (PTH) levels with lesser increases in serum calcium preserves the relationship between PTH levels and bone formation has not been evaluated. In addition, the impact of such treatment on the relative amounts of large amino-terminally truncated PTH fragments, such as PTH(7-84) has not been studied. Indeed, recent evidence suggests that these fragments affect the results obtained using the current available immunoradiometric (IRMA) PTH assays. The current application will compare the suppressive effect of treatment with calcitriol and one-alpha-hydroxy vitamin D2 (1aD2) on bone formation and parathyroid gland function in children with bone biopsy proven 2-HPT and treated with peritoneal dialysis. Also the response to these two vitamin D sterols will be assessed in patients given calcium carbonate or a new calcium-free phosphate-binding agent, sevelamar. Thus, patients will be randomized using a 2x2 factorial design to one of four treatment groups for eight months: 1aD2 plus calcium carbonate, 1aD2 plus sevelamar, calcitriol plus calcium carbonate and calcitriol plus sevelamar. Bone formation will be evaluated in cancellous bone by quantitative histomorphometry, and parathyroid gland function will be assessed by in vivo dynamic tests of PTH release. Serum PTH levels will be measured by two different immunoradiometric assays. In addition, expression of the mRNA encoding for collagen types II and X, alkaline phosphatase and the PTH/PTHrP receptor will be determined by in situ hybridization in growth plate obtained from iliac crest bone biopsy. The result of the study should provide new information on the regulation of bone formation and PTH by different vitamin D sterols in patients with 2-HPT.
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