Vitamin D supplementation for the management of knee osteoarthritis: A randomized controlled trial
C. Ding Osteoarthritis and Cartilage VOLUME 24, SUPPLEMENT 1, S49, APRIL 01, 2016
Purpose: Observational studies suggest potential benefits of vitamin D supplementation for knee osteoarthritis (KOA), but current trial evidence is contradictory.
The aim of this study was to compare the effects of vitamin D supplementation versus placebo on knee pain, knee cartilage volume and other structural changes in symptomatic KOA patients with low vitamin D levels.
Methods: A multicentre randomized, double-blind, placebo-controlled clinical trial in Australia. 413 patients (mean age 63.2 years, 51% females) with symptomatic KOA according to American College of Rheumatology criteria and low 25-hydroxyvitamin D (25OHD) (12.5 to 60 nmol/L) were included. Patients were randomly assigned to either monthly 50,000IU vitamin D3 (n = 209) or identical placebo (n = 204) for two years. Primary outcomes were change in tibial cartilage volume on MRI and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score from baseline to month 24. Secondary outcomes included knee pain by visual analogue scale (VAS), WOMAC function, and cartilage defects, bone marrow lesions (BMLs) and joint effusion-synovitis on MRI.
Results: 25OHD level increased more in the vitamin D group (40.6 vs. 6.7 nmol/L, p<0.001) over two years. There were no significant differences in annual tibial cartilage volume change (−3.44% vs. −4.23%, p = 0.132) or WOMAC pain score (−49.9 vs. −35.1, p = 0.102) though vitamin D group had less loss of cartilage volume and more improvement in knee pain. In secondary analyses, the vitamin D group had greater improvement in knee pain by VAS (−15.4 mm vs. −8.9 mm, p = 0.048) and WOMAC function (−170.2 vs. −97.3, p = 0.008) and more frequently achieved a 50% improvement in WOMAC pain (50% vs. 39%, p = 0.036). There were more OMERACT-OARSI responders in the vitamin D group than the place group (35% vs. 25%, p = 0.029). There were no significant differences in changes of tibiofemoral cartilage defects or BMLs; however, fewer of those receiving vitamin D had increases in BMLs (17% vs. 27%, p = 0.031). There was less increase in effusion-synovitis volume in the vitamin D group than controls (0.26 ml versus 2.20 ml, p = 0.02). The likelihoods of achieving a minimal clinical important improvement in total (relative risk: 1.22; p = 0.05) and suprapatellar (relative risk: 1.27 p.a.; p = 0.03) effusion-synovitis were significantly higher in vitamin D group compared to placebo. Adverse events were similar but numerically higher in the vitamin D group.
Conclusions: In patients with symptomatic KOA with low serum 25OHD, vitamin D supplementation over two years did not meet either primary endpoint. Secondary analyses suggest modest benefits on knee pain, physical function, BMLs and effusion-synovitis. Vitamin D supplementation has a higher responder rate than placebo.