title: 1 alpha-Hydroxy-vitamin D2: a new look at an 'old' compound.
abstract: Calcitriol is effective in suppressing PTH levels in haemodialysis patients with hyperparathyroidism but has a low therapeutic index. There is a search for other vitamin D sterols that suppress PTH but cause less hypercalcaemia. We review evidence that 1 alpha-hydroxy-vitamin D2 (1 alpha-D2) may be an effective and safer alternative to calcitriol. In vitamin D-deficient rats, 1 alpha-D2 is equipotent to 1 alpha-D3, which is converted to calcitriol before it acts; but, in normal rats, 1 alpha-D2 is much less toxic at high doses. In osteopenia models, either steroid-induced or following ovariectomy, 1 alpha-D2 is equal to or more effective than 1 alpha-D3 in preventing bone loss but causes less hypercalciuria. Studies in osteoporotic women reveal minimal hypercalciuria with 1 alpha-D2 at doses up to 4 micrograms/day, data suggesting greater safety than reported with calcitriol or 1 alpha-D3. Preliminary data in haemodialysis patients with secondary hyperparathyroidism demonstrate the efficacy of 1 alpha-D2 in suppressing PTH levels with minimal untoward effects on serum Ca and no effects on serum P. Taken together, these observations suggest that 1 alpha-D2 deserves strong consideration as a therapeutic agent for secondary hyperparathyroidism associated with end-stage renal disease.
authors.affiliation: Medical and Research Services, West Los Angeles Veterans Affairs, Medical Center (Wadsworth Division), CA 90073, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Coburn
authors.forename: A U
authors.initials: AU
authors.lastname: Tan
authors.forename: B S
authors.initials: BS
authors.lastname: Levine
authors.forename: R B
authors.initials: RB
authors.lastname: Mazess
authors.forename: D M
authors.initials: DM
authors.lastname: Kyllo
authors.forename: J C
authors.initials: JC
authors.lastname: Knutson
authors.forename: C W
authors.initials: CW
authors.lastname: Bishop
mesh_terms: D000818:Animals; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D051381:Rats; D006435:Renal Dialysis / Q000009:adverse effects
chemical_list: D004872:Ergocalciferols; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; C042533:1 alpha-hydroxyergocalciferol; C008088:alfacalcidol