Vitamin D status modifies the association between statin use and musculoskeletal pain: A population based study
Introduction
Statin use is associated with a higher risk for musculoskeletal pain [1]. Vitamin D status has been proposed to modify the effect of statin use on musculoskeletal pain, with deficient vitamin D increasing the risk of statin-associated musculoskeletal symptoms [2]. However, prior studies have included statin-users only, and have yielded mixed results [2], [3], [4], [5], [6]. Therefore, it remains uncertain whether vitamin D deficiency modifies the effect of statin use by increasing the risk of musculoskeletal pain beyond that associated with statin use or vitamin D deficiency alone, or, alternatively, whether any association exists after adjustment for important confounders. We aimed to examine the effect of vitamin D on the relationship between statin use and musculoskeletal pain in the general population.
Section snippets
Methods
For this cross-sectional study we analyzed data from the National Health and Nutrition Examination Survey (NHANES), an ongoing, cross-sectional survey that uses a complex, stratified, multistage, probability-cluster design to select a representative sample of the civilian, non-institutionalized US population. All participants gave written informed consent. Public use data files were obtained from the NHANES website, and our analyses of these de-identified data were approved for exemption by the
Results
Among 5907 participants ≥40 years, 1057 participants, representing 19.6 million individuals, reported statin use. The distribution of serum 25(OH)D for participants is depicted in Fig. 1. The mean serum 25(OH)D for the overall study population (23.6 ng/mL; 95% confidence interval [CI], 22.9–24.3) did not differ from the mean serum 25(OH)D among statin users (23.4 ng/mL; 95% CI, 22.3–24.4). Table 1 shows that participants with 25(OH)D <15 ng/mL, compared to those with higher levels of vitamin D,
Discussion
In this cross-sectional study of 5907 individuals, we found that vitamin D deficiency modified the effect of statin on musculoskeletal pain among adults ≥40 years. Specifically, individuals with 25(OH)D <15 ng/mL who were using a statin had a nearly 2 times greater odds of musculoskeletal pain within the past month compared to those with 25(OH)D <15 ng/mL who did not use a statin. In contrast, among adults who had serum 25(OH)D ≥15 ng/mL, use of statins was not associated with musculoskeletal
Conclusion
In this cross-sectional nationally-representative study of 5907 individuals, we found that among adults ≥40 years with vitamin D deficiency (25(OH)D<15 ng/mL), use of a statin was associated with a nearly 2 times greater odds of reporting musculoskeletal pain compared to non-statin users. However, among individuals with vitamin D levels ≥15 ng/mL, no association between statin use and musculoskeletal pain was observed. Our findings support the hypothesis that vitamin D deficiency modifies the
Funding sources
Dr. Buettner was supported by K23 Career Development Award (K23AR055664). Dr. Bertisch was supported by K23 Career Development Award (K23AT005104). This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources) and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102 and financial contributions from Harvard University and its affiliated academic
Disclosures
The authors' affiliated organizations and funding sources had no involvement in the study design; collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the article for publication. Dr. Buettner and Beth Israel Deaconess Medical Center have applied for a patent for the combination of statin and vitamin D as a prophylactic treatment in migraine. All other authors have no indicated no financial conflicts of interests.
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