Effects of 1 alpha-hydroxyvitamin D3 on various stages of predialysis renal bone disease

Biochemical parameters of mineral metabolism and bone histomorphometric measurements--both static and dynamic--were studied in 27 to 29 patients with chronic renal failure before (T0) and after 3 months treatment (T3) with 1 alpha-hydroxyvitamin D3 (1 alpha (OH)D3; average daily dose 0.55 micrograms). In none of the biopsies was a positive aluminum stain found. Fourteen patients had an osteoblast seams length (Ob.Pm) of less than 4% (Group I) and high osteoid parameters, whereas 13 patients (Group II, Ob.Pm greater than 4%) also had clear histological signs of hyperparathyroidism. Group II had lower creatinine clearance and serum calcium, but higher iPTH values. Treatment with 1 alpha (OH)D3 resulted in a substantial suppression of secondary hyperparathyroidism in Group II, with a fall in Ob.Pm, the cancellous bone perimeter occupied by tetracycline double label and osteoclast perimeter (Oc.Pm). In Group II treatment resulted in the development of a positive correlation between Ob.Pm and the number of osteoclasts (N.Oc). With treatment the (thionine) mineralization front rose in both groups, but osteoid seams length did not fall. When calculated for both groups together, before and after treatment serum calcium was negatively correlated with osteoid seams length, while a positive correlation was found with the mineralization front. This study provides an indication that, in progressive renal bone disease in which aluminum intoxication has been excluded, hyperosteoidosis precedes the development of secondary hyperparathyroidism. Furthermore, the study shows that treatment with 1 alpha (OH)D3 suppresses secondary hyperparathyroidism and results in a moderate increase of mineralization.