Long-term administration of vitamin D steroles in incipient and advanced renal failure: Effect on bone histology

In 36 patients with incipient and advanced renal failure (C(Cr) 80-20 ml/min x 1.73 m²), serum chemistry including ionized Ca, serum PTH and fractional intestinal absorption of Ca (whole body counter; two-dose-technique; ⁴⁷Ca p.o. and i.v. to correct for urinary and endogenous fecal loss were measured. Quantitative bone histology after in vivo tetracycline double labeling was evaluated from undecalcified sections before and 18 months after therapy with vitamin D₃ or 5,6-trans-25-OH-CC in a dose sufficient to raise intestinal absorption and/or urinary excretion of Ca. Intestinal absoption of Ca was impaired in some patients at a GFR of 60 ml/min/1.73 m². After up to 10 000 U/d 5,6-trans-25-OH-CC and 8000 IU/d vitamin D₃, respectively, fractional intestinal absorption of Ca rose and was normalized in all patients. There was a concomitant rise in urinary Ca. Serum PTH fell, but did not always return into the normal range. Ionized Ca rose in all patients. Bone histology was evaluated in 17 of these 36 patients informed consent was obtained. The mass of mineralized bone (Vv) rose in 7/17 patients, pointing to a positive calcium balance. Volumetric density of osteoid (Vvos) and surface density of osteoid (Svos) fell in 10/17 patients concomitant with an increase in the fraction of mineralizing seams and a decrease in the number of lamellae in osteoid seams. Osteoclastic resorption (O(Cl) fell as did the fraction of woven osteiod seams. However, woven osteoid failed to disappear completely and osteoclastic resorption stayed elevated in some patients. 5,6-trans-25-OH-CC and vitamin D₃, in doses that normalized intestinal absorption of Ca, failed to restore completely bone histology to normal although mineralization and collagen texture of osteoid were consistently improved. The dose response characteristics to vitamin D of different abnormalities of Ca metabolism appear to be non-uniform.