Effect of Vitamin D Supplementation on Depressive Symptoms in Patients With Knee Osteoarthritis

Shuang Zheng, Liudan Tu, Flavia Cicuttini, Weiyu Han, Zhaohua Zhu, Benny Antony, Anita Wluka, Tania Winzenberg, Tao Meng, Dawn Aitken, Leigh Blizzard, Graeme Jones, Changhai Ding

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20 Citations (Scopus)


Objectives: To determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depressive symptoms in patients with knee osteoarthritis (OA) and vitamin D deficiency. Design: A prespecified secondary analysis of a multicentre, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive oral vitamin D3 (50,000 IU, n = 209) or placebo (n = 204) monthly for 24 months. In addition, participants who completed the trial were classified into 2 groups according to their serum 25(OH)D levels at month 3 and 24 as follows: not consistently sufficient (serum 25(OH)D ≤ 50 nmol/L at month 3 and/or 24), and consistently sufficient (serum 25(OH)D > 50 nmol/L at both month 3 and 24). Multilevel mixed-effect models were used to compare differences of change in PHQ-9 scores between groups. Setting and Participants: This clinical trial was conducted in participants with symptomatic knee OA and vitamin D deficiency from June 2010 to December 2013 in Tasmania and Victoria, Australia. Measures: The primary outcome was the depressive symptoms change over 24 months, which was measured using the Patient Health Questionnaire (PHQ-9, 0-27). Results: Of 599 participants who were screened for eligibility, 413 participants were enrolled (mean age: 63.2 years; 50.3% female) and 340 participants (intervention n = 181, placebo n = 159, 82.3% retention rate) completed the study. The baseline prevalence of depression (PHQ-9 score ≥5) was 25.4%. Depressive symptoms improved more in the vitamin D supplementation group compared to the placebo group [β: −0.66, 95% confidence interval (CI): −1.22 to −0.11, P for difference =.02] and in the participants who maintained vitamin D sufficiency compared to those who did not (β: −0.73, 95% CI: −1.41 to −0.05, P for difference =.04) over 24 months. Conclusions/Implications: These findings suggest that vitamin D supplementation and maintaining adequate vitamin D levels over 24 months may be beneficial for depressive symptoms in patients with knee OA.

Original languageEnglish
Pages (from-to)1634-1640.e1
Number of pages8
Issue number12
Publication statusPublished - Dec 2019


  • depressive symptoms
  • osteoarthritis
  • vitamin D deficiency
  • Vitamin D supplementation

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