title: Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory.
  
  
  OBJECTIVE
  To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels.
  
  
  METHODS
  A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013.
  
  
  METHODS
  Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years.
  
  
  METHODS
  Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI).
  
  
  RESULTS
  Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text].
  
  
  CONCLUSIONS
  Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01176344; anzctr.org.au Identifier: ACTRN12610000495022.
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Xingzhong
authors.initials: X
authors.lastname: Jin
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Graeme
authors.initials: G
authors.lastname: Jones
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Flavia
authors.initials: F
authors.lastname: Cicuttini
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Anita
authors.initials: A
authors.lastname: Wluka
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Weiyu
authors.initials: W
authors.lastname: Han
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Benny
authors.initials: B
authors.lastname: Antony
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia3Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Tania
authors.initials: T
authors.lastname: Winzenberg
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Leigh
authors.initials: L
authors.lastname: Blizzard
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia2Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia4Arthritis Research Institute and Department of Rheumatology.
authors.forename: Changhai
authors.initials: C
authors.lastname: Ding
mesh_terms: D018771:Arthralgia / Q000188:drug therapy*; D002356:Cartilage / Q000033:anatomy & histology / Q000187:drug effects*; D002762:Cholecalciferol / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007719:Knee Joint; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood / Q000188:drug therapy*; D010147:Pain Measurement; D013648:Tasmania; D013977:Tibia; D014739:Victoria; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D