Long-term effects of 1,25-dihydroxy vitamin D3 and 24,25-dihydroxy vitamin D3 in renal osteodystrophy

Twenty-three patients with end-stage renal failure on maintenance haemodialysis were treated with 1,25-dihydroxy vitamin D3 or 24-25-dihydroxy vitamin D3 for 3-32 months (total 232 patient months). Treatment with 1,25-dihydroxy vitamin D3 was marked by symptomatic, biochemical and histological improvements in the majority of patients. In contrast, treatment with 24,25-dihydroxy vitamin D3 produced no biochemical or histological improvements and such patients developed severe symptomatic bone disease. Successful renal transplantation resulted in rapid improvement in symptoms, biochemistry and bone histology in nine of 10 patients irrespective of whether prior treatment was with 1,25-dihydroxy vitamin D3, 24,25-dihydroxy vitamin D3 or both. During treatment with 1,25-dihydroxy vitamin D3 progressive reduction in dosage was required in the majority of patients because of hypercalcaemia, which was rapidly corrected by stopping treatment for a few days. Hypercalcaemia did not occur until serum alkaline phosphatase (AP) and amino terminal parathyroid hormone (N-PTH) had fallen towards normal. Treatment failure was uncommon in 1,25-dihydroxy vitamin D3-treated patients and was characterized by the early development of hypercalcaemia. Addition of 24,25-dihydroxy vitamin D3 in such patients rendered the hypercalcaemia more manageable but did not lead to any further improvement in biochemistry or bone histology. Treatment with 24,25-dihydroxy vitamin D3 was accompanied by the development of severe symptomatic bone disease in the majority of patients and a characteristic pattern of biochemical abnormalities with hypocalcaemia and rises in AP and N-PTH. Substitution of 1,25-dihydroxy vitamin D3 treatment for 24,25-dihydroxy vitamin D3 in these patients resulted in prompt improvement in clinical, biochemical and histological abnormalities. Successful renal transplantation was accompanied by rapid resolution of clinical, biochemical and histological features of renal osteodystrophy irrespective of whether previous treatment was with 1,25-dihydroxy vitamin D3 or 24,25-dihydroxy vitamin D3. Hypophosphataemia was common in the early months after renal transplantation without evidence of continuing hyperparathyroidism. The studies have confirmed that 1,25-dihydroxy vitamin D3 is effective in controlling clinical, biochemical and histological features of renal osteodystrophy while 24,25-dihydroxy vitamin D3 did not have a useful therapeutic effect in the dose used.