Growth of long bones in renal failure: Roles of hyperparathyroidism, growth hormone and calcitriol

Growth of long bones in renal failure: Roles of hyperparathyroidism, growth hormone and calcitriol.BackgroundThe treatment of secondary hyperparathyroidism (2°HPT) associated with chronic renal failure adversely affects skeletal growth.MethodsWe assessed epiphyseal growth plate morphology by quantitative histology and measured mRNA levels for selected markers of chondrocyte proliferation and differentiation by in situ hybridization in the growth plate cartilage of subtotally nephrectomized rats with either mild or advanced 2°HPT.ResultsThe width of the growth plate cartilage in the proximal tibia and mRNA levels for PTH/PTHrP receptor were unchanged in rats with mild 2°HPT, however, they were markedly less in nephrectomized rats with advanced 2°HPT than in intact controls. Treatment with growth hormone 10IU/kg/day increased growth plate thickness both in mild and in advanced 2°HPT and raised mRNA levels for type II and type X collagen in rats with advanced 2°HPT. The administration of calcitriol 50ng/kg/day attenuated these responses in animals with advanced 2°HPT. Overall, PTH/PTHrP receptor mRNA levels did not correspond to the serum levels of PTH indicating that PTH/PTHrP receptor expression is down-regulated in renal failure by a PTH-independent mechanism.ConclusionCalcitriol counteracts the trophic actions of growth hormone on epiphyseal growth plate cartilage and modifies chondrocyte differentiation in vivo, and these mechanisms may contribute to disturbances in longitudinal bone growth in renal failure