GROWTH OF LONG BONES IN RENAL-FAILURE - ROLES OF HYPERPARATHYROIDISM,GROWTH-HORMONE AND CALCITRIOL

Background The treatment of secondary hyperparathyroidism (2 degrees H PT) associated with chronic renal failure adversely affects skeletal g rowth. Methods. We assessed epiphyseal growth plate morphology by quan titative histology and measured mRNA levels for selected markers of ch ondrocyte proliferation and differentiation by in situ hybridization i n the growth plate cartilage of subtotally nephrectomized rats with ei ther mild or advanced 2 degrees HPT. Results. The width of the growth plate cartilage in the proximal tibia and mRNA levels for PTH/PTHrP re ceptor were unchanged in rats with mild 2 degrees HPT, however, they w ere markedly less in nephrectomized rats with advanced 2 degrees HPT t han in intact controls. Treatment with growth hormone 10 IU/kg/day inc reased growth plate thickness both in mild and in advanced 2 degrees H PT and raised mRNA levels for type II and type X collagen in rats with advanced 2 degrees HPT. The administration of calcitriol 50 ng/kg/day attenuated these responses in animals with advanced 2 degrees HPT. Ov erall, PTH/PTHrP receptor mRNA levels did not correspond to the serum levels of PTH indicating that PTH/PTHrP receptor expression is down-re gulated in renal failure by a PTH-independent mechanism. Conclusion. C alcitriol counteracts the trophic actions of growth hormone on epiphys eal growth plate cartilage and modifies chondrocyte differentiation in vivo, and these mechanisms may contribute to disturbances in longitud inal bone growth in renal failure.