Background
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
Methods
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.
Status
This is an ongoing project and the protocol is in preparation.