Review finds vitamin D lacks disease-modifying effect in rheumatic diseases

A new review from the International Osteoporosis Foundation (IOF) Osteoimmunology Working Group, published in Osteoporosis International, provides a comprehensive evaluation of the role of vitamin D in inflammatory rheumatic diseases. The authors conclude that that while vitamin D deficiency is common and clinically important, current evidence does not support a direct disease-modifying effect.

The review, "Vitamin D in inflammatory rheumatic diseases: still a challenge," examined data from randomized controlled trials, observational studies, systematic reviews, and meta-analyses involving conditions such as rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthritis, systemic sclerosis, and Sjögren's disease. It found that between 40% and 80% of patients with inflammatory rheumatic diseases have insufficient vitamin D levels, with deficiency associated with higher disease activity, fatigue, pain, and poorer musculoskeletal outcomes. While vitamin D supplementation consistently corrected deficiency safely and showed modest benefits in disease activity in some patients, particularly in those with low baseline vitamin D levels, the evidence overall was heterogeneous and inconsistent.

Importantly, large, randomized trials and Mendelian randomization studies did not confirm a causal role for vitamin D in preventing disease onset or sustaining remission.

Vitamin D remains an important component of comprehensive care for patients with inflammatory rheumatic diseases, particularly for bone and muscle health. However, despite promising biological mechanisms and observational associations, the current evidence indicates that vitamin D supplementation should not be viewed as a stand-alone disease-modifying therapy."

Professor Patricia Clark, corresponding author, Faculty of Medicine UNAM, Mexico

Professor Osvaldo Messina, IRO Clinical Research and Regenerative Medicine Center, Argentina, and co-chair of the Osteology Working Group, added. "Our review underscores the need for better-designed randomized trials to clarify who may benefit most. There is a need for future large-scale studies that can stratify patients according to baseline vitamin D deficiency and genetic background to better understand the causal mechanisms and the long-term effect of vitamin D repletion in inflammatory rheumatic diseases."

The authors emphasize that maintaining serum 25-hydroxyvitamin D concentrations of at least 30 ng/mL remains advisable for skeletal health, in line with recommendations from the International Osteoporosis Foundation and other international bodies. However, whether higher vitamin D levels provide clinically meaningful immunological benefits remains uncertain.

Several unresolved questions in the field were also noted, including:

• Whether vitamin D deficiency contributes directly to disease mechanisms or primarily reflects chronic inflammation;
• The optimal serum vitamin D thresholds for immune modulation;
• The long-term effects and safety of higher-dose supplementation strategies.

Professor Eugene McCloskey, University of Sheffield, UK and Chair of the IOF Committee of Scientific Advisors, acknowledged the significant contribution of the authors and the IOF Osteoimmunology Working Group in compiling and critically evaluating the current evidence base, noting that: "The review helps to clarify the ongoing challenges and future research priorities in this complex field."