Impaired growth, delayed ossification, and reduced osteoclastic activity in the growth plate of calcium-supplemented rats with renal failure

Linear growth is reduced in prepubertal children with adynamic renal osteod ystrophy, suggesting that the proliferation and/or differentiation of epiph yseal growth plate chondrocytes is abnormal in this disorder. To examine th is issue, in situ hybridization and histochemistry were used to measure sel ected markers of endochondral bone formation and bone resorption in the pro ximal tibia of subtotally nephrectomized rats fed a high calcium diet to in duce biochemical changes consistent with adynamic osteodystrophy. Blood ion ized calcium concentrations were higher and serum PTH levels were lower in nephrectomized, calcium-supplemented rats than in either intact or nephrect omized control animals. Linear growth and tibial length were reduced, but m essenger RNA levels for type II collagen, type X collagen, and the PTH/PTHr P receptor did not differ from control values in nephrectomized rats given supplemental calcium. In contrast, both the width of epiphyseal cartilage a nd the height of the zone of hypertrophic chondrocytes were greater in calc ium-supplemented nepkrectomized rats. These morphological changes were asso ciated with decreases in histochemical staining for tartrate-resistant acid phosphatase and lower levels of messenger RNA expression for the matrix me talloproteinase MMP-9/gelatinase B immediately adjacent to the epiphyseal g rowth plate. Diminished chondroclastic/osteoclastic activity alters growth plate morphology and adversely affects linear bone growth in calcium-supple mented, nephrectomized rats.