Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial.
What this study found
Vitamin D supplementation raised 25-hydroxyvitamin D levels but did not provide meaningful clinical or structural benefit for knee osteoarthritis over 2 years. Mean plasma 25-hydroxyvitamin D increased from 22.7 to 38.5 ng/mL in the vitamin D group versus 21.9 to 24.7 ng/mL with placebo, and 61.3% versus 8.3% reached at least 36 ng/mL by month 24 (P<.001). However, knee pain fell by about 2 points in both groups with no significant time-treatment interaction (P=.22), and cartilage volume loss was about 4% over 2 years in both groups with no significant between-group differences in cartilage…
- Study & population
- Randomized, placebo-controlled, single-center trial in adults aged 45 years or older with symptomatic radiographic knee osteoarthritis (Kellgren-Lawrence grades 2-4) and at least mild knee pain.
- Intervention
- Oral cholecalciferol (vitamin D3) 2000 IU daily was given initially for 2 years, with 2000-IU dose adjustments at 4, 8, and 12 months to target a 25-hydroxyvitamin D level of 36 to 100 ng/mL.
- Key limitation
- Single-center design and a modest active-arm sample size limit generalizability.
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Open PDFOriginal abstract
IMPORTANCE Knee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression. OBJECTIVE To determine whether vitamin D supplementation reduces symptom and structural progression of knee OA. DESIGN, SETTING, AND PATIENTS A 2-year randomized, placebo-controlled, double-blind, clinical trial involving 146 participants with symptomatic knee OA (mean age, 62.4 years [SD, 8.5]; 57 women [61%], 115 white race [79%]). Patients were enrolled at Tufts Medical Center in Boston between March 2006 and June 2009. INTERVENTION Participants were randomized to receive either placebo or oral cholecalciferol, 2000 IU/d, with dose escalation to elevate serum levels to more than 36 ng/mL. MAIN OUTCOME MEASURES Primary outcomes were knee pain severity (Western Ontario and McMaster Universities [WOMAC] pain scale, 0-20: 0, no pain; 20, extreme pain), and cartilage volume loss measured by magnetic resonance imaging. Secondary end points included physical function, knee function (WOMAC function scale, 0-68: 0, no difficulty; 68, extreme difficulty), cartilage thickness, bone marrow lesions, and radiographic joint space width. RESULTS Eighty-five percent of the participants completed the study. Serum 25-hydroxyvitamin D levels increased by a mean 16.1 ng/mL (95% CI, 13.7 to 18.6) in the treatment group and by a mean 2.1 mg/mL (95% CI, 0.5 to 3.7) (P < .001) in the placebo group. Baseline knee pain was slightly worse in the treatment group (mean, 6.9; 95% CI, 6.0 to 7.7) than in the placebo group (mean, 5.8; 95% CI, 5.0 to 6.6) (P = .08). Baseline knee function was significantly worse in the treatment group (mean, 22.7; 95% CI, 19.8 to 25.6) than in the placebo group (mean, 18.5; 95% CI, 15.8 to 21.2) (P = .04). Knee pain decreased in both groups by a mean -2.31 (95% CI, -3.24 to -1.38) in the treatment group and -1.46 (95% CI, -2.33 to -0.60) in the placebo group, with no significant differences at any time. The percentage of cartilage volume decreased by the same extent in both groups (mean, -4.30; 95% CI, -5.48 to -3.12 vs mean, -4.25; 95% CI, -6.12 to -2.39) (P = .96). There were no differences in any of the secondary clinical end points. CONCLUSION AND RELEVANCE Vitamin D supplementation for 2 years at a dose sufficient to elevate 25-hydroxyvitamin D plasma levels to higher than 36 ng/mL, when compared with placebo, did not reduce knee pain or cartilage volume loss in patients with symptomatic knee OA. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00306774.