Effectiveness of vitamin D supplementation on knee osteoarthritis - A target trial emulation study using data from the Osteoarthritis Initiative cohort.

ABSTRACT

OBJECTIVE: To assess the real-world effectiveness of vitamin D supplementation in patients with knee osteoarthritis (KOA) by replicating a randomized controlled trial (RCT) design in an observational study. METHOD: This study emulated a target trial using data from the Osteoarthritis Initiative (OAI). Eligible participants were ≥45 years, had symptomatic KOA and did not take vitamin D supplements in the past 30 days. A participant can enter the trial more than once. Participants were included in vitamin D group if they took ≥1,000 IU/day for ≥4 days/week in the past 30 days at the first follow-up visit after baseline. The control group did not use vitamin D in the past 30 days. Optimal propensity score matching at 11 ratio was performed. The primary outcome was change in knee pain 2 years after baseline measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included WOMAC physical function and quantitative joint space width (JSW). Standardized mean difference (SMD) was used to compare the findings with previous RCTs. RESULTS: A total of 236 person-trials in the vitamin D group were pair-matched with a control. Compared to the control group, vitamin D supplementation did not reach significant changes in WOMAC pain (SMD = -0.04, 95%CI [-0.21, 0.13]), physical function and radiographic JSW over 2 years. The SMDs were consistent with the effect sizes reported in previous RCTs. CONCLUSION: Target trial emulation in the OAI cohort demonstrated findings close to published RCTs. This supports the future use of target trial emulation in evaluating other systemic therapies for KOA.