title: The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial.
abstract: BACKGROUND
  Homocysteine has been postulated as a novel, potentially reversible risk factor for osteoporosis and related fractures. We evaluated whether homocysteine-lowering therapy with B-vitamins in patients with symptomatic cerebrovascular disease reduced the incidence of osteoporotic fractures.
  
  
  METHODS
  VITAmins To Prevent Stroke (VITATOPS) was a prospective randomised double-blind placebo-controlled trial in which 8,164 patients with recent (within 7 months) stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of either placebo (n = 4,075) or B-vitamins (folic acid 2 mg, vitamin B6 25 mg, vitamin B12 500 μg; n = 4,089). Patients were reviewed every six months. Any osteoporotic fracture and osteoporotic hip fractures were secondary outcome events, and were reviewed by a masked adjudication committee. Analysis was by intention to treat. Logistic regression was used to identify independent predictors of fracture.
  
  
  RESULTS
  Participants had a mean age of 62.6 years (SD 12.5 years) and 64% were male, 42% of Western European descent and 75% were functionally independent (Oxford Handicap Scale of two or less). After a median duration of 2.8 years therapy and 3.4 years follow-up, there was no significant difference in the incidence of any osteoporotic fracture between participants assigned B-vitamins (67 [1.64%]) and placebo (78 [1.91%]; risk ratio [RR] 0.86, 95% confidence interval [CI] 0.62-1.18) or the incidence of hip fractures (34 [0.83%] B-vitamins vs. 36 [0.88%] placebo; RR 0.94, 95% CI 0.59-1.5). There was no significant impact of B-vitamin therapy on time to first fracture. Baseline homocysteine levels did not predict any osteoporotic fracture (p =0.43). Independent predictors of any osteoporotic fracture were female sex, age > 64 years, Western European ethnicity and use of anti-osteoporosis medication at randomization (all p < 0.01).
  
  
  CONCLUSIONS
  Once daily treatment with B-vitamins had no effect on incidence of osteoporotic fractures during a median of 3.4 years follow-up in patients with cerebrovascular disease. A modest effect of B-vitamin therapy is not excluded due to the low numbers of fracture outcome events.
authors.affiliation: Department of Medicine, Hawke's Bay Hospital, Hastings, New Zealand. john.gommans@hbdhb.govt.nz.
authors.forename: John
authors.initials: J
authors.lastname: Gommans
authors.forename: Qilong
authors.initials: Q
authors.lastname: Yi
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
authors.forename: Helen
authors.initials: H
authors.lastname: Rodgers
mesh_terms: D000368:Aged; D015415:Biomarkers; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control; D011446:Prospective Studies; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D014803:Vitamin B Complex