title: Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls.
abstract: Our objective was to conduct a systematic review on the benefits and harms of calcitriol and alfacalcidol in the reduction of fracture and fall risk. Randomized controlled trials (RCTs) comparing these agents to placebo or calcium and reporting fracture and fall incidence were retrieved from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Two reviewers independently determined study eligibility, assessed trial quality, and extracted data. Twenty-three RCTs were included (2139 participants), and 16 trials had sufficient data for meta-analysis. Vertebral fractures were not significantly reduced based on the combined results of 13 trials; however, subgroup analyses demonstrated a significant reduction with alfacalcidol [odds ratio (OR) = 0.50, 95% confidence interval (CI), 0.25-0.98], but not with calcitriol. There was a significant reduction in nonvertebral fractures (six trials, OR = 0.51, 95% CI, 0.30-0.88), and falls (two trials, OR = 0.66, 95% CI, 0.44-0.98). There was an increased risk of hypercalcemia (OR = 3.63, 95% CI, 1.51-8.73) and a trend toward an increased risk of hypercalciuria. There is evidence to suggest that these agents may reduce the incidence of nonvertebral fractures and falls; however, their benefit on vertebral fracture reduction may depend on the type of active vitamin D. Hypercalcemia and hypercalciuria are potential side effects.
authors.affiliation: Clinical Epidemiology Program, Ottawa Health Research Institute, 1053 Carling Avenue, ASB 1-006, Ottawa, Ontario, Canada, K1Y 4E9. odonnell.sioban1@gmail.com
authors.forename: Siobhan
authors.initials: S
authors.lastname: O'Donnell
authors.forename: David
authors.initials: D
authors.lastname: Moher
authors.forename: Kelli
authors.initials: K
authors.lastname: Thomas
authors.forename: David A
authors.initials: DA
authors.lastname: Hanley
authors.forename: Ann
authors.initials: A
authors.lastname: Cranney
mesh_terms: D000058:Accidental Falls / Q000517:prevention & control*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002117:Calcitriol / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D050723:Fractures, Bone / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D016239:MEDLINE; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; D010919:Placebos; D002117:Calcitriol; D002118:Calcium; C008088:alfacalcidol