Vitamin D Deficiency Prevalent Among Patients with Rheumatic Disease

Elvis Hysa, MD

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A high prevalence of vitamin D serum deficiency or insufficiency was observed in patients with inflammatory and autoimmune rheumatic diseases, which may be linked to adverse muscle health outcomes, according to research published in Nutrients.¹

Vitamin D is known for its role in regulating plasma concentrations of calcium and phosphate, which aid in maintaining a healthy mineralized skeleton. However, it is also an important feature in the modulation of the immune system and inflammatory responses, which may be a beneficial factor in immune-related disorders.²

“Vitamin D status has been also found to have a significant association with muscle health. Many studies have consistently shown that vitamin D deficiency (plasma concentrations < 10 ng/mL) or insufficiency (plasma concentrations < 30 ng/mL) are linked to various negative effects on muscle health including the loss of muscle strength, musculoskeletal pain, sarcopenia and increased risk of falls,” wrote a team of investigators led by Elvis Hysa, MD, a rheumatologist associated with the Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa.¹ “The body of evidence suggests that this hormone might exert a protective role on muscle health not only in terms of muscle regeneration and mitochondrial health but also by exhibiting anti-inflammatory properties."

To better understand the impact of impaired vitamin D status on muscle function and its function in inflammatory and autoimmune rheumatic diseases, investigators conducted a comprehensive search using data from PubMed and Medline to identify relevant studies involving vitamin D, rheumatic diseases, and the muscles. Conference abstracts from the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) were also reviewed. Although the review focused on evidence published within the last 5 years, investigators chose to incorporate any significant studies from earlier years as well. Eligible studies were those that linked vitamin D to muscle health among these inflammatory and autoimmune diseases.

Results of the database searches revealed a high prevalence of vitamin D deficiency or insufficiency among this patient population. These included idiopathic inflammatory myopathies (IIMs), polymyalgia rheumatica, and a variety of autoimmune connective tissue diseases such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). IIMs were of particular interest to investigators as they represent a group of muscle disorders defined by chronic inflammation that can lead to progressive muscle weakness.

These studies demonstrated vitamin D insufficiency was linked to reduced muscle strength, increased pain, higher disease activity, fatigue, and worsened disease outcomes.However, the quality of evidence as well as the different associations for the diseases were heterogeneous.

SSc was shown to have the greatest amount of data evaluating the impact of vitamin D among autoimmune connective tissue diseases. Among patients with SLE, 92% demonstrated pathological reduced serum levels, which could be a consequence of the disease process itself and/or due to clinicians advising patients to avoid sunlight. Vitamin D insufficiency and deficiency among patients with RA was associated with poorer locomotive functions, which could be indicative of the vitamin’s impact on muscle health. Most of the studies involving patients with RA showed a potential link between vitamin D deficiency and the development of the rheumatic disease, as well as an inverse correlation between vitamin D status and disease activity.

Data showed adequate levels of vitamin D serum concentrations aid in protective effects on muscle health. Several translational and clinical studies indicated active metabolites play an active role in not only reducing inflammation, but also enhancing muscle regeneration, mitochondrial function, and intra-cellular metabolism. However, interventional studies identified and included in the analysis were limited and investigators mentioned a need for more robust longitudinal studies to confirm these findings. Future research can also help to establish optimal vitamin D supplementation strategies personalized to particular patient populations.

“While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold,” investigators concluded.¹

References

1. ^{Hysa E, Gotelli E, Campitiello R, et al. Vitamin D and Muscle Status in Inflammatory and Autoimmune Rheumatic Diseases: An Update. Nutrients. 2024;16(14):2329. Published 2024 Jul 19. doi:10.3390/nu16142329}
2. ^{Cutolo, M.; Smith, V.; Paolino, S.; Gotelli, E. Involvement of the secosteroid vitamin D in autoimmune rheumatic diseases and COVID-19. Nat. Rev. Rheumatol. 2023, 19, 265–287.}