The Effect of Vitamin D Supplementation on Pain and Physical Function in Patients with Knee Osteoarthritis


Observational data suggest vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). Vitamin D supplementation may be a promising cost-effective treatment. Yet, randomized clinical trials (RCTs) to date investigating the effectiveness of vitamin D supplementation in knee OA have found controversial results. Recent systematic reviews with aggregate data from these RCTs suggest that current evidence does not support vitamin D supplementation for slowing structural progression of the disease, however, further research is needed to clarify the effects on patient-reported outcomes. The aim of this study is to identify patient-level predictors of treatment response to vitamin D supplementation on pain and physical function, in order to see whether particular patient subgroups are more likely to benefit from vitamin D treatment than others. A systematic literature search will be conducted for randomized clinical trials comparing vitamin D supplementation with other control treatments in individuals with knee osteoarthritis. Authors of original trials will be contacted to obtain individual patient data from each study


The primary outcomes will include long-term (≥12 months) pain and physical function. Secondary outcomes will include medium-term (≥ 6 months and < 12 months) and short-term (<6 months) pain and physical function, as well as patient global assessment and quality of life. Potential treatment effect modifiers to be examined in the subgroup analyses include age, gender, body mass index, baseline knee pain severity and physical function, baseline vitamin D level, radiographic disease stage, presence of bone marrow lesions on MRI, and presence of clinical signs of local inflammation or effusion-synovitis. Both one-step and two-step modelling methods will be used to determine the possible modifiable effect of each subgroup of interest.


This is an ongoing project and the protocol is in preparation.

Protocol and publications


X. (Xingzhong) Jin 1
B. (Benny) Antony 2
X. (Xia) Wang 3
T. (Timothy) E. McAlindon 4
N. (Nigel) Arden 5
R. (Rajeshwar) Nath Srivastava 6
M. (Marienke) van Middelkoop 7
S. (Sita) M.A. Bierma-Zeinstra 7
W. (Weiya) Zhang 8
C. (Changhai) Ding 2

1. The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, the University of Sydney, Australia
2. Menzies Institute for Medical Research, University of Tasmania, Australia
3. Institute of Bone & Joint Research, the University of Sydney, Australia
4. Tufts Medical Center, United States
5. Nuffield Department Orthopaedic, Rheumatology and musculoskeletal sciences, University of Oxford, United Kingdom
6. Department of Orthopedic Surgery, King George Medical University, India
7. Department of General Practice, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
8. Faculty of Medicine & Health Sciences, University of Nottingham, United Kingdom