Quantitative Histological Studies on the Pathogenesis of Uremic Bone Disease*

Abstract

Twenty-two patients with chronic uremia were separated into 3 groups on the basis of quantitative bone histology: 1) mild (10 patients); 2) osteomalacic (6); and 3) fibrotic (6). In the mild group there was an increase in forming surface; in the osteomalacic group, a delayed onset of mineralization; in the fibrotic group, increases in marrow fibrosis, bone formation and resorption. Since duration of renal disease was much shorter in the mild group, it was considered a precursor of the other 2 groups. In addition there were positive correlations between a number of bone parameters and duration of renal disease. Since duration of renal disease was similar in the osteomalacic and fibrotic groups, one did not appear to be an intermediate form of the other. The mineralization defect was confined to the osteomalacic group, but was not due to hypocalcemia, since serum calcium was normal and did not differ among the 3 groups. Most of the changes in the mild and fibrotic groups (increases in forming surface, resorbing surface and marrow fibrosis) could be ascribed to excess parathyroid hormone (PTH). In some uremic patients there was an inverse relationship between resorbing surface and serum calcium as would be expected in secondary hyperparathyroidism. In others, however, serum calcium and resorbing surface were directly related, suggesting that PTH secretion may have been determined by factors in addition to serum calcium.