1-ALPHA-HYDROXY-VITAMIN-D2 - A NEW LOOK AT AN OLD COMPOUND

Calcitriol is effective in suppressing PTH levels in haemodialysis pat ients with hyperparathyroidism but has a low therapeutic index. There is a search for other vitamin D sterols that suppress PTH but cause le ss hypercalcaemia. We review evidence that 1 alpha-hydroxy-vitamin D-2 (1 alpha-D-2) may be an effective and safer alternative to calcitriol . In vitamin D-deficient rats, 1 alpha-D-2 is equipotent to 1 alpha-D- 3, which is converted to calcitriol before it acts; but, in normal rat s, 1 alpha-D-2 is much less toxic at high doses. In osteopenia models, either steroid-induced or following ovariectomy, 1 alpha-D-2 is equal to or more effective than 1 alpha-D-3 in preventing bone loss but cau ses less hypercalciuria. Studies in osteoporotic women reveal minimal hypercalciuria with 1 alpha-D-2 at doses up to 4 mu g/day, data sugges ting greater safety than reported with calcitriol or 1 alpha-D-3. Prel iminary data in haemodialysis patients with secondary hyperparathyroid ism demonstrate the efficacy of 1 alpha-D-2 in suppressing PTH levels with minimal untoward effects on serum Ca and no effects on serum P. T aken together, these observations suggest that 1 alpha-D-2 deserves st rong consideration as a therapeutic agent for secondary hyperparathyro idism associated with end-stage renal disease.