Modulation of endochondral bone formation: roles of growth hormone, 1,25-dihydroxyvitamin D and hyperparathyroidism

Impairment of linear growth occurs invariably in children with chronic rena l failure. Recombinant human growth hormone and 1,25-dihydroxyvitamin D (ca lcitriol) are widely utilized to improve linear growth in children. Large d oses of calcitriol, however, have been shown to suppress chondrocyte prolif eration and may lead to the development of adynamic bone. Substantial reduc tions of growth have been shown in children with chronic renal failure trea ted with intermittent calcitriol therapy. These findings suggest that calci triol can modify chondrocyte proliferation and/or differentiation in epiphy seal growth plate cartilage and may counteract the effects of growth hormon e therapy in increasing linear growth in children with chronic renal failur e. Parathyroid hormone related peptide (PTHrP) and its receptor (PTH/PTHrP receptor) play critical roles in regulating chondrocyte differentiation in the growth plate. The expression of PTH/PTHrP receptor mRNA is downregulate d in animals with chronic renal failure and advanced secondary hyperparathy roidism; calcitriol and growth hormone therapy may modify the expression of PTH/PTHrP receptor. This article summarizes the separate and combined effe cts of growth hormone and calcitriol on endochondral bone formation in chro nic renal failure and secondary hyperparathyroidism.