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      Vitamin D Serum Levels in Patients with Statin-Induced Musculoskeletal Pain

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          Abstract

          Introduction

          Statin-associated muscle symptoms are common side effects of statin therapy. These symptoms include myopathy, myalgia, and rhabdomyolysis. Vitamin D has been associated with musculoskeletal health; thus, its deficiency may produce detrimental effects in this tissue. Indeed, one symptom of vitamin D deficiency is myalgia, and the normalization of low vitamin D levels can relieve it.

          Patients and Methods

          This cross-sectional study examined 1210 statin-treated patients to assess vitamin D status. These patients were divided into two groups: 287 with statin-associated muscle symptoms (SAMS) and 923 control patients without SAMS.

          Results

          We have found a significant association between deficient and insufficient vitamin D status and statin-associated muscle symptoms (SAMS). Vitamin D deficiency (<30 nmol/L) presents 77% (95% C.I. 71.6% to 81.7%) sensitivity and 63.4% (95% C.I. 60.2% to 66.5%) specificity in diagnosing SAMS. Odds ratio analysis showed that this association is moderate-strong both for deficient and for insufficient status.

          Conclusion

          We found a correlation between vitamin D deficiency and SAMS. Therefore, vitamin D levels may be useful for the diagnosis and management of SAMS.

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          Most cited references25

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          Vitamin D3: a helpful immuno-modulator.

          The active metabolite of vitamin D, 1α, 25-dihydroxyvitamin D3 [1,25(OH)(2) D3], is involved in calcium and phosphate metabolism and exerts a large number of biological effects. Vitamin D3 inhibits parathyroid hormone secretion, adaptive immunity and cell proliferation, and at the same time promotes insulin secretion, innate immunity and stimulates cellular differentiation. The role of vitamin D3 in immunoregulation has led to the concept of a dual function as both as an important secosteroid hormone for the regulation of body calcium homeostasis and as an essential organic compound that has been shown to have a crucial effect on the immune responses. Altered levels of vitamin D3 have been associated, by recent observational studies, with a higher susceptibility of immune-mediated disorders and inflammatory diseases. This review reports the new developments with specific reference to the metabolic and signalling mechanisms associated with the complex immune-regulatory effects of vitamin D3 on immune cells. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.
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            Management of Statin Intolerance in 2018: Still More Questions Than Answers

            Statin therapy is generally well tolerated and very effective in the prevention and treatment of cardiovascular disease, regardless of cholesterol levels; however, it can be associated with various adverse events (myalgia, myopathy, rhabdomyolysis, and diabetes mellitus, among others). Patients frequently discontinue statin therapy without medical advice because of perceived side effects and consequently increase their risk for cardiovascular events. In patients with statin intolerance, it may be advisable to change the dose, switch to a different statin, or try an alternate-day regimen. If intolerance is associated with all statins—even at the lowest dose—non-statin drugs and certain nutraceuticals can be considered. This review focuses on the definition of statin intolerance and on the development of clinical and therapeutic strategies for its management, including emerging alternative therapies.
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              Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages.

              Vitamin D3 [1α,25-(OH)(2)D(3)], involved in the regulation of body calcium homeostasis, promotes immature myeloid precursor cells differentiation into monocytes/macrophages. In this study we compared the regulatory interaction between 1α,25-(OH)(2)D(3) and tumor necrosis factor (TNF)-α or lipopolysaccharide (LPS) in the mRNA expression of interleukin (IL)-1β, (IL)-6, TNF-α, toll like receptors (TLR)-2 and (TLR)-4 in freshly isolated human monocyte (MonoT0) and in macrophages cultured for seven days (MØT7). Additionally, we detected the effect of 1α,25-(OH)(2)D(3) on macrophages chemotaxis. The expression of IL-1β, IL-6 and TNF-α, as well as TLR-2 and TLR-4 in MonoT0 and in MØT7 was examined by real time RT-PCR. Macrophages chemotaxis was analyzed by using horizontal chemotaxis agarose spot assay. We found that 1α,25-(OH)(2)D(3) influences macrophages chemotaxis and differently modulates the expression of IL-1β, IL-6, TNF-α and TLRs in the two different stages of monocytes/macrophage maturation. In conclusion our data add new information about the role of 1α,25-(OH)(2)D(3) on the expression of inflammatory mediators in human monocyte/macrophages, underlying the complex function of these cells. Investigating the differences in the pattern of expression of immune-mediators produced by MonoT0 and MØT7 may provide a new way to examine their biochemical and molecular function and may constitute a model system with well-defined behavior with respect to early or tardive events in the innate immune response. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2019
                25 March 2019
                : 2019
                : 3549402
                Affiliations
                1Spinal Unit, Emergency Hospital Cannizzaro, Catania, Italy
                2Research Center “The Great Senescence”, University of Catania, 95100 Catania, Italy
                3Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, Catania, Italy
                4Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy
                5Oasi Research Institute-IRCCS, Via Conte Ruggero, 73-94018 Troina, Italy
                Author notes

                Academic Editor: Mariann Harangi

                Author information
                http://orcid.org/0000-0003-0776-1411
                http://orcid.org/0000-0003-3655-4307
                http://orcid.org/0000-0001-8332-6863
                http://orcid.org/0000-0002-5659-662X
                http://orcid.org/0000-0002-7145-6377
                Article
                10.1155/2019/3549402
                6452565
                a5193f27-850d-423b-99f4-e81387dea37f
                Copyright © 2019 Manuela Pennisi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 December 2018
                : 27 January 2019
                Funding
                Funded by: Ministero dell'Istruzione, dell'Università e della Ricerca
                Categories
                Research Article

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