Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial.

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. For the vitamin D arm, 73 participants were randomized, 64 completed, and 73 were analyzed in the primary analyses; the study focused on the more severely affected knee in each participant.

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. The regimen did not include calcium supplementation.

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 thickness, bone marrow lesion size, or radiographic joint space width. Serious and overall adverse events were similar between groups.

Single-center design and a modest active-arm sample size limit generalizability. Attrition occurred in the vitamin D arm (73 randomized, 64 completed), and several structural and subgroup findings were secondary or subset analyses, which reduces certainty around small effects.