title: Vitamin K supplementation for the primary prevention of osteoporotic fractures: is it cost-effective and is future research warranted?
abstract: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. It would be a cost-effective intervention at commonly used thresholds, but high uncertainty around the cost-effectiveness estimates persists. Further research on the effect of vitamin K on fractures is warranted.
  
  
  BACKGROUND
  Vitamin K might have a role in the primary prevention of fractures, but uncertainties about its effectiveness and cost-effectiveness persist.
  
  
  METHODS
  We developed a state-transition probabilistic microsimulation model to quantify the cost-effectiveness of various interventions to prevent fractures in 50-year-old postmenopausal women without osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and calcium (at the same doses). An additional analysis explored replacing vitamin K(2) with vitamin K(1) (5 mg/day).
  
  
  RESULTS
  Adding vitamin K(2) to vitamin D(3) with calcium reduced the lifetime probability of at least one fracture by 25%, increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95% credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 95% and the population expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin K(1) to vitamin D and calcium reduced the lifetime probability of at least one fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4) and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the EVPI was $414.9 billion. The efficacy of vitamin K was the most important parameter in sensitivity analyses.
  
  
  CONCLUSIONS
  Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. Given high uncertainty around the cost-effectiveness estimates, further research on the efficacy of vitamin K on fractures is warranted.
authors.affiliation: Department of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Gajic-Veljanoski
authors.forename: A M
authors.initials: AM
authors.lastname: Bayoumi
authors.forename: G
authors.initials: G
authors.lastname: Tomlinson
authors.forename: K
authors.initials: K
authors.lastname: Khan
authors.forename: A M
authors.initials: AM
authors.lastname: Cheung
mesh_terms: D050071:Bone Density Conservation Agents / Q000191:economics / Q000627:therapeutic use*; D002118:Calcium / Q000191:economics / Q000627:therapeutic use; D002170:Canada / Q000453:epidemiology; D002762:Cholecalciferol / Q000191:economics / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D019587:Dietary Supplements; D016527:Drug Costs / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination; D005260:Female; D017048:Health Care Costs / Q000706:statistics & numerical data*; D006801:Humans; D008875:Middle Aged; D017059:Models, Econometric; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy / Q000191:economics; D058866:Osteoporotic Fractures / Q000191:economics / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D016896:Treatment Outcome; D010837:Vitamin K 1 / Q000191:economics / Q000627:therapeutic use; D024482:Vitamin K 2 / Q000191:economics / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D024482:Vitamin K 2; D002762:Cholecalciferol; D010837:Vitamin K 1; D002118:Calcium