Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis
Authors: Xingzhong Jin, Graeme Jones, Flavia Cicuttini, Anita Wluka, Zhaohua Zhu, Weiyu Han, Benny Antony, Xia Wang, Tania Winzenberg, Leigh Blizzard, Changhai Ding
Journal: JAMA (2016)

<h3>Importance</h3> Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> Participants were randomly assigned to receive monthly treatment with oral vitamin D<sub>3</sub>(50 000 IU; n = 209) or an identical placebo (n = 204) for 2 years. <h3>Main Outcomes and Measures</h3> 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). <h3>Results</h3> 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) (<i>P</i> &lt; .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%}];<i>P</i> = .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}];<i>P</i> = .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}];<i>P</i> = .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}];<i>P</i> = .06). Adverse events (≥1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (<i>P</i> = .04). <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01176344; anzctr.org.au Identifier:ACTRN12610000495022