The association of serum 25-hydroxyvitamin D status and statin-associated musculoskeletal symptoms
Morioka, Travis Y
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Objectives: In this study, we investigated the relationship between serum vitamin D status and the prevalence of musculoskeletal pain among individuals on statin therapy. We hypothesized that lower serum vitamin D concentration would be associated with a higher odds of self-reported musculoskeletal pain among statin users. Background: HMG-CoA reductase inhibitors, or statins, are widely used lipid-lowering drugs that significantly reduce morbidity and mortality associated with heart disease. Statin use is associated with a higher prevalence of self-reported musculoskeletal pain in the general population. Non-blinded studies have shown improvement in statin-associated myalgia symptoms and increased tolerance to statin therapy after treatment of vitamin D deficiency. Methods: We performed secondary data analyses using the National Health and Nutrition Examination Survey (NHANES) 2001-2004. Employing SAS and SUDAAN, we carried out logistic regression to evaluate whether vitamin D deficiency modified the relationship between statin use and musculoskeletal pain. Based on a priori assumptions, we adjusted for the effects of demographics, selected disease states, and health habits in the logistic regression model. We also explored concentration-related trends of the effect of vitamin D on musculoskeletal pain. Results: Among 5941 participants age 40 years and older, the mean serum vitamin D concentration was 23.5 ng/mL [95% Confidence Interval (CI) 22.4, 24.2]. There was no significant difference in the mean serum vitamin D concentration between statin users (23.3 ng/mL, 95% CI 22.3, 24.3) and non-statin users (23.5 ng/mL, 95% CI 22.8, 24.2). Statin users had higher odds [adjusted odds ratio (aOR) 1.57, 95% CI 1.15, 2.13)] of self-reported musculoskeletal pain in any area (specifically including the lower extremities, lower back, upper extremities, and upper back) compared with non-users. Vitamin D deficiency was not a predictor of musculoskeletal pain (aOR 0.95, 95% CI 0.70, 1.28) in the overall sample. However, we found vitamin D deficiency to have a significant interaction with statin use for the outcome of musculoskeletal pain (p for interaction = 0.01). After stratifying the sample according to statin use, we found that compared to statin users with a vitamin D concentration of 15 ng/mL or higher, those using statins with vitamin D concentration less than 15 ng/mL demonstrated substantially higher odds of musculoskeletal pain (aOR 2.56, 95% CI 1.25, 5.25). Assessment of vitamin D as a continuous variable did not reveal a concentration-related trend between increasing vitamin D concentrations and musculoskeletal pain (p for trend = 0.4). Conclusions: After controlling for multiple confounders, our analyses showed that serum vitamin D concentration less than 15 ng/mL was associated with musculoskeletal pain among statin users. However, among those not using statins, no association between serum vitamin D levels and self-reported musculoskeletal pain was demonstrated. We showed that vitamin D deficiency modifies the relationship between statio use and musculoskeletal pain. Treating vitamin D deficiency has other proven benefits including, bone health and skeletal muscle function. Our data suggests it may be reasonable to identify and treat vitamin D deficiency in patients who report musculoskeletal pain, using statins.
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