Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial | Geriatrics | JAMA | JAMA Network
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Original Investigation
March 8, 2016

Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial

Author Affiliations
  • 1Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
  • 2Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
  • 3Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia
  • 4Arthritis Research Institute and Department of Rheumatology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
JAMA. 2016;315(10):1005-1013. doi:10.1001/jama.2016.1961
Abstract

Importance  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.

Design, Setting, and Participants  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.

Interventions  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.

Main Outcomes and Measures  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 (−3.4% in the vitamin D group vs −4.2% in the placebo group [between-group difference, 0.8% {95% CI, −0.2% to 1.8%}]; P = .13) or WOMAC pain score (−49.9 in the vitamin D group vs −35.1 in the placebo group [between-group difference, −14.8 {95% CI, −32.5 to 2.9}]; P = .10). There were no significant differences in change of tibiofemoral cartilage defects (0.3 in the vitamin D group vs 0.5 in the placebo group [between-group difference, −0.2 {95% CI, −0.4 to 0.1}]; P = .21) or change in tibiofemoral bone marrow lesions (−0.1 in the vitamin D group vs 0.3 in the placebo group [between-group difference, −0.5 {95% CI, −0.9 to 0.0}]; P = .06). Adverse events (≥1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04).

Conclusions and Relevance  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.

Trial Registration  clinicaltrials.gov Identifier: NCT01176344; anzctr.org.au Identifier: ACTRN12610000495022

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