Review Article
Bone Health, Vitamin D and Lupus
Salud ósea, vitamina D y lupus
Clara Sangüesa Gómez, Bryan Josué Flores Robles, José Luis Andréu
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Sección de Enfermedades Autoinmunes Sistémicas, Servicio de Reumatología, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain
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Significant advances in treatment, achieving a more efficient control of inflammatory disease activity, have led to a progressive increase in the life expectancy of patients. Unfortunately, most of them gradually accumulate irreversible damage during the course of the disease, which compromises their quality of life and reduces life expectancy, the latter at the expense primarily of accelerated atherosclerosis. The development of osteoporosis and the appearance of associated fractures are very important components of irreversible damage, accrued in the medium and long term, and hypovitaminosis D<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">1</span></a> may be involved in its development.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Vitamin D is a steroid hormone that plays a crucial role in mineral metabolism and bone homeostasis, interacting with the parathyroid gland, kidney and gut. Although historically it has been classified as an essential diet-obtained vitamin, vitamin D can be synthesized in humans and most mammals endogenously, its main source being the conversion of 7-dehydrocholesterol to provitamin D3 in the skin through ultraviolet B radiation from the sun. Through exposure to ultraviolet light, provitamin D3 becomes previtamin D3, which is isomerized to vitamin D2 and transported to the bloodstream. In the liver, 25-hydroxylase converts vitamin D2 quickly into 25 (OH) D2 and 25 (OH) D3 (calcidiol), considered as storage forms of vitamin D. Both the 25 (OH) D2 and 25 (OH) D3 forms are released into the blood. In renal tubular cells, 1-alpha-hydroxylase converts 25 (OH) D3 into1,25 (OH)<span class="elsevierStyleInf">2</span> D3 or calcitriol, which is the biologically active compound, increasing intestinal absorption of calcium and phosphate, increasing bone mineralization and stimulating osteoclast differentiation. Activity of 1-alpha-hydroxylase is stimulated by PTH and hypocalcemia and is suppressed by serum calcitriol and phosphate. The presence of 1-alpha-hydroxylase in various tissues and in different cells of the immune system has been recently described, making possible, at least in theory, <span class="elsevierStyleItalic">in situ</span> production of calcitriol, with potential autocrine or paracrine effects.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Numerous studies in different regions of the world have shown that vitamin D insufficiency is a very common problem at all ages and results from the combination of a number of factors such as race, degree of sun exposure, latitude, aging and intake of vitamin D.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">3</span></a> In addition to the role of vitamin D deficiency in the development or severity of osteoporosis, information on the potential link between vitamin D deficiency and various autoimmune diseases, hypertension and some cancers<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">3</span></a> is accumulating. In recent years, the discovery of the vitamin D receptor (VDR) in immune cells as well as the fact that many of these cells endogenously produce calcitriol suggest that it may have four immunoregulatory properties. The inhibitory properties on cell proliferation, enhancement of cell differentiation, anti-inflammatory and immunomodulation roles of synthetic VDR agonists could be used to treat a variety of autoimmune diseases such as rheumatoid arthritis, SLE, multiple sclerosis and inflammatory bowel disease.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">5</span></a> Moreover, vitamin D deficiency could divert the immune response to a loss of tolerance<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">4</span></a> making the treatment of vitamin D deficiency particularly important in patients with lupus. In fact, a direct relationship between lupus activity and states of hypovitaminosis D has been proposed.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The objective of this narrative review is to analyze and integrate the latest relevant information on the implications of vitamin D deficiency in patients with SLE, both regarding bone health as well as the implications on autoimmunity and atherosclerosis.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Vitamin D Deficiency and Lupus</span><p id="par0025" class="elsevierStylePara elsevierViewall">Calcidiol concentration in serum is the most accepted indicator of the reserve of vitamin D in the body. However, this determination is not standardized and there is no general consensus regarding what serum reference values are. Although vitamin D insufficiency was initially defined as a mild form of vitamin D deficiency that leads to hyperparathyroidism and decreased bone mass without osteomalacia or hypocalcemia, currently vitamin D insufficiency has been redefined as a concentration below 70<span class="elsevierStyleHsp" style=""></span>nmol/L (30<span class="elsevierStyleHsp" style=""></span>ng/ml) without reference to the levels of PTH in July.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">7</span></a> Although there is controversy regarding the optimal level of vitamin D, current information from observational and biochemical studies and randomized clinical trials indicates that serum levels of at least 50<span class="elsevierStyleHsp" style=""></span>nmol/L are required to normalize PTH, minimize the risk of osteomalacia and ensure optimal cell function.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">There is a relationship between vitamin D deficiency and various autoimmune diseases. In fact, populations farthest from the equator are at increased risk of developing autoimmune diseases.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">9</span></a> We have solid evidence on the association between SLE or rheumatoid arthritis and vitamin D deficiency, although there is also probably an association with other chronic inflammatory rheumatic diseases.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">10</span></a> Studies in groups of patients with autoimmune rheumatic diseases have shown a high prevalence of low levels of vitamin D. Thus, 1029 patients with various autoimmune diseases such as scleroderma, polymyositis, dermatomyositis, antiphospholipid syndrome, rheumatoid arthritis or SLE had lower levels of calcidiol than healthy controls.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">11</span></a> However, one must take into account the heterogeneity of the cutoff points used in different studies and possible confounding factors associated with various diseases, such as glucocorticoid treatment, photosensitivity or recommendations to avoid sun exposure.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients with lupus often exhibit photosensitivity, implying a higher risk of developing vitamin D deficiency. Multiple studies investigating the possible association between the insufficiency or deficiency of vitamin D and lupus have shown that vitamin D insufficiency is a very common problem in this group of patients, with a wide range of prevalence, from 16% to 96%.<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">12–20</span></a> There are many factors potentially involved in the development of hypovitaminosis D, among which we find the advice to avoid sun exposure in patients with photosensitivity; the use of sun protection measures; renal failure; prolonged use of corticosteroids, antimalarials or antiepileptic drugs; or the presence of antibodies antivitamin D.</p><p id="par0040" class="elsevierStylePara elsevierViewall">As far back as in 1979 Canadian researchers determined calcitriol levels in 12 adolescents with SLE and found reduced levels in 7 patients. However, levels of calcidiol, which is the best marker of vitamin D available<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">21</span></a> was not informed.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In a cross-sectional study in 25 patients with SLE and 25 Caucasian women with fibromyalgia there were no significant differences between the 2 groups regarding calcidiol, calcitriol and PTH determinations, with half of the patients showing vitamin D deficiency.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">22</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In a Danish case–control study, calcidiol and calcitriol levels were measured in 21 patients with SLE, 29 patients with rheumatoid arthritis, 12 patients with osteoarthritis and 72 healthy controls; researchers found significantly lower calcidiol levels in lupus patients than in osteoarthritis patients or healthy controls while calcitriol levels between groups did not differ significantly.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">23</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In a cohort study of 123 patients with newly diagnosed SLE and 240 controls, a trend towards lower levels of vitamin D was detected in SLE patients compared with controls, with a significant difference between white subjects with the control group, after adjusting for age, sex, season and smoking. Overall, 67% of subjects had vitamin D deficiency, with a reduced mean concentration among black subjects (1 5.9<span class="elsevierStyleHsp" style=""></span>ng/ml) compared with Caucasians (31.3<span class="elsevierStyleHsp" style=""></span>ng/ml). In 22 patients, critically low levels were observed, below 10<span class="elsevierStyleHsp" style=""></span>ng/ml, the most powerful predictor of renal involvement (OR 13.3; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.01) followed by photosensitivity (OR 12.9; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.01).<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">6</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In our Mediterranean environment, Muñoz Ortego et al.,<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">24</span></a> reported a prospective cohort of 73 patients with SLE who were not receiving vitamin D, in which 68.5% had vitamin D levels below 30<span class="elsevierStyleHsp" style=""></span>ng/mL. Predictors found were daily use of sunscreen and a high rate of bone mass. Instead, they showed no association between low levels of vitamin D and lupus activity or accumulated damage.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">24</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In another Spanish cohort of 92 patients (90% female and 98% white) with lupus, Ruiz Irastorza et al.,<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">12</span></a> found a prevalence of deficiency and insufficiency of vitamin D of 15 and 75%, respectively. Predictors of adequate levels of vitamin D were treatment with vitamin D and calcium (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.049), female gender (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.001) and treatment with hydroxychloroquine (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.014). Photosensitivity and photoprotection were significantly associated with vitamin D insufficiency and deficiency, respectively. Vitamin D deficiency was associated with greater fatigue but vitamin D levels were not associated with the severity of SLE or duration of the disease.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Bone Health and Lupus</span><p id="par0070" class="elsevierStylePara elsevierViewall">The causes of bone loss in SLE include traditional risk factors of osteoporosis as well as side effects on bone because of long-term use of corticosteroids and immunosuppressive drugs. However, the disease itself may condition a reduced bone mass through mechanisms such as decreased mobility, deterioration of renal function, associated endocrine dysfunction or systemic proinflammatory stimulatory cytokine effect on bone resorption.<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">25,26</span></a> Recognizing the major contributing factors for bone loss in these patients could allow the early detection of osteoporosis and optimize bone health of patients, minimizing the risk of fracture.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Lupus patients exhibit decreased bone mineral density (BMD) and increased risk of fracture.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">25</span></a> By some estimates, the frequency of osteopenia and osteoporosis could range up to 50% and 23%, respectively.<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">26,27</span></a> Despite some inconsistent data between different cross-sectional studies, most of the available information supports the association between low BMD and lupus, even in young fertile women.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Teichman et al.,<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> studied lumbar spine and hip BMD in a group of 20 premenopausal women diagnosed with lupus of less than a year. Comparing this data with healthy controls of the same age, women newly diagnosed with SLE had significantly lower lumbar spine BMD but no significant differences were observed on the femoral neck.</p><p id="par0085" class="elsevierStylePara elsevierViewall">In a study conducted by Norwegian researchers<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">29</span></a> BMD similarly decreased at the lumbar spine, femoral neck and total hip when comparing 75 lupus patients with 75 patients with rheumatoid arthritis, even when stratifying for menopausal status. All patients in the study were white and mostly women. No significant differences in body mass index, use of disease-modifying drugs or cytotoxic agents in patients with low BMD were observed.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Kipen et al.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">30</span></a> assessed changes in BMD in 32 premenopausal women with SLE, with a mean age of 35 years, showing only minimal changes in lumbar spine and femoral neck BMD. Physical activity was a protective factor against BMD loss of the femoral neck.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In a similar study, Jardinet et al.,<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">31</span></a> observed a significant decrease in lumbar spine BMD from baseline from 1.22% per year in 35 women of childbearing age with SLE and a mean age of 30 years, after a mean follow-up of 21 months. However, they found no difference in the change in hip BMD. The patients had a significantly lower baseline BMD than age-matched healthy controls.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Jacobs et al.,<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">32</span></a> recently published a longitudinal study with the largest number of patients enrolled till date: 126 patients with SLE, 90% female, mean age 39 years. At baseline, 39.7% of patients had osteopenia and 6.3% osteoporosis. After a mean follow-up of 6 years, changes in lumbar spine (−0.08%/year) and hip BMD (−0.20%/year) were not significant compared to baseline. During follow-up, 70% of patients were treated with glucocorticoids. The multiple regression analysis showed that the decrease in lumbar spine BMD was significantly associated with glucocorticoid dose and reduced levels of vitamin D. The loss of bone mass in the hip was associated with lower levels of the vitamin, to a lower body mass index and the use of antimalarials at the start of follow-up.</p><p id="par0105" class="elsevierStylePara elsevierViewall">There are few studies evaluating fracture risk in patients with SLE. In a population of 702 women (mean age 33.2 years) with SLE followed for an average of 8 years, Ramsey-Goldman et al.,<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">33</span></a> showed that 12.3% of women had at least one fracture non-attributable to severe trauma after the diagnosis of SLE.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Vitamin D, Immune Response and Clinical Activity in Lupus</span><p id="par0110" class="elsevierStylePara elsevierViewall">Despite the numerous studies published on LES and vitamin D, a question to be answered is whether vitamin D deficiency aggravates the course of disease. This is the point most recent published studies have focused on, reflecting some inconsistency in the findings. These conflicting results could be explained by the diversity of the study populations, methodological variations or that some studies are underpowered due to the number of patients included.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">34</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The discovery of the VDR on most cells of the immune system suggests a number of immunomodulating actions related to vitamin D. <span class="elsevierStyleItalic">In vitro</span> studies have shown that calcitriol modulates both innate and adaptive immune responses. Vitamin D increases the chemotaxis and phagocytosis of macrophages and increases the production of IL-12 and IL-13, leading to a change of polarization of T cells by altering their phenotype Th1 and Th17 to Th2. Calcitriol also inhibits B cell differentiation to plasma cells and immunoglobulin production of IgM and IgG isotypes.<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">35</span></a> In SLE, many of the immunomodulatory actions of vitamin D are opposite to those observed with disease activity, so one hypothesis states that vitamin D deficiency could be considered a risk factor for development that arises or perpetuation of activity in SLE. However, this attractive hypothesis could not be confirmed in a study conducted in a cohort of more than 180,000 US nurses.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">36</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Petri et al.,<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">37</span></a> studied the association between vitamin D levels and different parameters of activity in a prospective cohort of 1006 patients with SLE (91% female, 54% white) that were followed for a mean of 128 weeks. Patients with lower levels of calcidiol 40<span class="elsevierStyleHsp" style=""></span>ng/ml were supplemented with 50,000 units of vitamin D2 weekly. An increase of 20 units in calcidiol levels was associated with a decrease in the rate of SELENA–SLEDAI activity of 0.22 points, which corresponded with a 21% decrease in the <span class="elsevierStyleItalic">odds ratio</span> of presenting a higher SLEDAI SELENA-4. Moreover, the mean protein/creatinine ratio decreased by 2% (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0009), which corresponded with a 15% decrease in the <span class="elsevierStyleItalic">odds ratio</span> of presenting a protein/creatinine ratio greater than 0.5.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Borba et al.,<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">19</span></a> found no association between lupus activity, measured by the SLEDAI-2 K index, and the levels of IL-6, IL-1 and TNF α and with low levels of vitamin D in 36 patients with SLE. Furthermore, the multiple regression analysis showed that reduced levels of calcidiol were associated to elevated levels of osteocalcin and bone alkaline phosphatase.</p><p id="par0130" class="elsevierStylePara elsevierViewall">In another study, Amital et al.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">13</span></a> determined calcidiol levels in 378 patients with SLE and related to the SLEDAI-2 K activity indices in 278 patients and ECLAM in 100 patients. They concluded that there was a significant negative correlation between serum vitamin D levels and standardized disease activity since, although the association was weak, statistical significance was reached.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Mok et al.,<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">38</span></a> studied the sensitivity and specificity of vitamin D deficiency as a predictor of systemic lupus activity and damage compared with classical markers of activity, such as the concentration of anti-native DNA and anti-C1q antibodies in a cohort of 290 patients with SLE, 95% female, with a mean age of 39 years and a mean disease duration of 7.7 years. They concluded that vitamin D deficiency was a marker of SLE activity, with comparable levels of anti-C1q antibody specificity. However, they found no significant association between calcidiol deficiency and accumulated systemic organ damage.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Thudi et al. reported that<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">39</span></a> 20% of SLE patients had calcidiol levels of less than 47.7<span class="elsevierStyleHsp" style=""></span>nmol/l. These patients had a significantly higher mean disease activity, including overall evaluation indices, than patients with normal levels of vitamin D.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Recently, Sakthiswary and Raymond<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">34</span></a> have published a systematic review of the clinical significance of vitamin D in lupus. They identified eight case–control studies and 14 cohort studies. Of the 15 studies linking vitamin D and SLE activity, 10 showed an inverse relationship between vitamin D levels and lupus activity. In relation to the accumulated disease damage, 5 of 6 studies investigating the association found no significant difference. The authors concluded that there was sufficient evidence on the association between the states of vitamin D deficiency and SLE disease activity but not with indices of cumulative damage.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Vitamin D and Cardiovascular Risk in Lupus</span><p id="par0150" class="elsevierStylePara elsevierViewall">Vitamin D deficiency has been linked to coronary artery disease, heart failure and kidney disease.<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">40–42</span></a> Ischemic heart disease is a leading cause of death in patients with SLE, so it is very important to identify factors associated with the development of atherosclerosis in lupus patients.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Mok et al.,<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">38</span></a> in their sample of 290 patients, showed that subjects with vitamin D deficiency (<15<span class="elsevierStyleHsp" style=""></span>ng/ml) had a significantly higher ratio LDL cholesterol/total cholesterol. These findings are consistent with those of Wu et al.,<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">18</span></a> who showed a correlation between high levels of LDL-cholesterol and low levels of vitamin D. Reynolds et al.,<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">43</span></a> and Ravenell et al.,<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">44</span></a> have published contradictory results on the correlation with carotid atheroma plaque. Ravenell et al. showed that vitamin D levels correlated inversely with the total area of plaque when age-adjusted, while Reynolds et al. could not demonstrate this association, although a significant increase in aortic stiffness was associated with low levels of vitamin D.</p><p id="par0160" class="elsevierStylePara elsevierViewall">In a study of Kiani et al.,<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">45</span></a> no significant association between vitamin D levels and any measure of subclinical atherosclerosis and coronary calcification quantified by CT, or thickness of carotid intima-media measured by ultrasound was found in 154 patients with SLE.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Supplementation With Vitamin D in Lupus</span><p id="par0165" class="elsevierStylePara elsevierViewall">30–40<span class="elsevierStyleHsp" style=""></span>ng/ml are considered the minimum desirable calcidiol serum levels since lower concentrations lead to different degrees of hyperparathyroidism. To standardize the concentration of vitamin D, doses of about 10 000<span class="elsevierStyleHsp" style=""></span>U daily vitamin D2 are required and 3 months of treatment.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">3</span></a> Calcium supplements and vitamin D are clearly indicated in some situations such as rickets or in the context of the use of drugs for osteoporosis. However, in other clinical situations there may be doubts on the advisability of supplementation.<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">46</span></a> A meta-analysis of 18 studies with randomized controlled trials showed that patients receiving vitamin D had a reduction in mortality versus<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">47</span></a> patients in the placebo group.</p><p id="par0170" class="elsevierStylePara elsevierViewall">From the immunological point of view, it has been observed that vitamin D deficiency diverts the immune response to a loss of tolerance. The addition of vitamin D reversed immunological abnormalities characteristic of SLE<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">48</span></a> and supplementation induces beneficial clinical and immunological effects in experimental models of SLE.<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">49</span></a> Some authors advocate treatment with vitamin D as prevention of autoimmune disease perpetuation. In this respect Abou-Raya et al.,<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">48</span></a> carried out a randomized, double-blind, placebo-controlled trial with a population of 267 SLE patients (228 women, 39 men, mean age 38.8 years, mean disease duration 8.2 years) and determined vitamin D homeostasis and inflammatory markers and parameters of disease activity before and after administration of vitamin D. The average baseline calcidiol was 19.8<span class="elsevierStyleHsp" style=""></span>ng/ml in patients compared with 28.7<span class="elsevierStyleHsp" style=""></span>ng/ml in controls. The overall prevalence of baseline suboptimal levels and calcidiol deficiency in SLE patients and controls was 69 and 39%, respectively. The suboptimal vitamin D levels were significantly correlated with lupus activity. At 12 months of treatment, a significant improvement in the levels of inflammation and homeostasis, as well as disease activity in the treatment group compared to the placebo, was seen.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="par0175" class="elsevierStylePara elsevierViewall">Vitamin D is essential for many body tissues and is involved in numerous biological processes beyond bone metabolism. There is sufficient epidemiological evidence that shows that low levels of vitamin D are associated with various medical conditions, particularly with autoimmune diseases. The demonstration of a higher prevalence of vitamin D deficiency in SLE patients compared with healthy controls, coupled with the recent discovery of its immunomodulating properties in both innate and adaptive responses, has attracted interest in this field with the objective of demonstrating a clinical role of vitamin D in the course of SLE. SLE patients have a higher prevalence of osteopenia and osteoporosis, even in young premenopausal women, as a result of various factors, among which the use of glucocorticoids, vitamin D deficiency and the activity of the disease are included. It is essential to identify these factors early to reduce the risk of fracture. Although recent data suggest the existence of an association between states of vitamin D deficiency and SLE activity, there is still neither enough evidence to affirm categorically that an association exists nor has the impact of substitution treatment with vitamin D on the activity of the disease been fully understood. Therefore, prospective randomized controlled therapeutic intervention studies are needed.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Ethical disclosures</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Protection of human and animal subjects</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Confidentiality of data</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Right to privacy and informed consent</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflict of Interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to state.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres528608" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec548848" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres528607" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec548847" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Vitamin D Deficiency and Lupus" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Bone Health and Lupus" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Vitamin D, Immune Response and Clinical Activity in Lupus" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Vitamin D and Cardiovascular Risk in Lupus" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Supplementation With Vitamin D in Lupus" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 11 => array:3 [ "identificador" => "sec0040" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Right to privacy and informed consent" ] ] ] 12 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflict of Interest" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-08-28" "fechaAceptado" => "2014-10-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec548848" "palabras" => array:3 [ 0 => "Systemic lupus erythematosus" 1 => "Vitamin D" 2 => "Osteoporosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec548847" "palabras" => array:3 [ 0 => "Lupus eritematoso sistémico" 1 => "Vitamina D" 2 => "Osteoporosis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The prevalence of vitamin D deficiency and insufficiency among patients with systemic lupus erythematosus is high. This is likely due to photoprotection measures in addition to intrinsic factors of the disease. Low levels of vitamin D increase the risk of low bone mineral density and fracture. Vitamin D deficiency could also have undesirable effects on patients’ immune response, enhancing mechanisms of loss of tolerance and autoimmunity. Vitamin D levels should be periodically monitored and patients should be treated with the objective of reaching vitamin D levels higher than 30–40<span class="elsevierStyleHsp" style=""></span>ng/ml.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con lupus eritematoso sistémico presentan una prevalencia elevada de deficiencia e insuficiencia de vitamina D. Esto se debe probablemente a las medidas de fotoprotección y a factores intrínsecos de la enfermedad. Los niveles bajos de vitamina D aumentan el riesgo de presentar una densidad mineral ósea reducida y de fractura. El déficit de vitamina D podría también tener efectos no deseados sobre la respuesta inmune de los pacientes, potenciando mecanismos de pérdida de tolerancia y autoinmunidad. Los niveles de vitamina D deberían ser monitorizados periódicamente y los pacientes deberían ser tratados con el objetivo de alcanzar unos niveles de vitamina D superiores a 30–40<span class="elsevierStyleHsp" style=""></span>ng/ml.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sangüesa Gómez C, Flores Robles BJ, Andréu JL. Salud ósea, vitamina D y lupus. Reumatol Clin. 2015;11:232–236.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:49 [ 0 => array:3 [ "identificador" => "bib0250" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Accrual of organ damage over time in patients with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.D. Gladman" 1 => "M.B. Urowitz" 2 => "P. Rahman" 3 => "D. Ibañez" 4 => "L.S. Tam" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Rheumatol" "fecha" => "2003" "volumen" => "30" "paginaInicial" => "1955" "paginaFinal" => "1959" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12966597" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534709034028" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0255" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D and systemic lupus erythematosus: state of the art" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Schneider" 1 => "A.S. Dos Santos" 2 => "M. Santos" 3 => "R.M. da Silva Chakr" 4 => "O.A. Monticielo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-014-2530-5" "Revista" => array:7 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2014" "volumen" => "33" "paginaInicial" => "1033" "paginaFinal" => "1038" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24573738" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0090429511006273" "estado" => "S300" "issn" => "00904295" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0260" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Salud ósea y mucho más" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Larrosa Padró" 1 => "D. Vitamina" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1699-258X(07)73686-0" "Revista" => array:7 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2007" "volumen" => "3" "paginaInicial" => "197" "paginaFinal" => "199" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21794430" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0302283809002371" "estado" => "S300" "issn" => "03022838" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0265" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D and autoimmune rheumatic diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Cutolo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/ken394" "Revista" => array:6 [ "tituloSerie" => "Rheumatology" "fecha" => "2009" "volumen" => "48" "paginaInicial" => "210" "paginaFinal" => "212" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18930963" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0270" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Control of autoimmune diseases by the vitamin D endocrine system" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Adorini" 1 => "G. Penna" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ncprheum0855" "Revista" => array:7 [ "tituloSerie" => "Nat Clin Pract Rheumatol" "fecha" => "2008" "volumen" => "4" "paginaInicial" => "404" "paginaFinal" => "412" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18594491" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534708003170" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0275" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamina D deficiency in systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.L. Kamen" 1 => "G.S. Cooper" 2 => "H. Bouali" 3 => "S.R. Shaftman" 4 => "B.W. Hollis" 5 => "G.S. Gilkeson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autrev.2005.05.009" "Revista" => array:6 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2006" "volumen" => "5" "paginaInicial" => "114" "paginaFinal" => "117" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16431339" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0280" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D and musculoskeletal health" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.E. Wolff" 1 => "A.N. Jones" 2 => "K.E. Hansen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ncprheum0921" "Revista" => array:6 [ "tituloSerie" => "Nat Clin Pract Rheumatol" "fecha" => "2008" "volumen" => "4" "paginaInicial" => "580" "paginaFinal" => "588" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18852718" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0285" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D and bone health: epidemiologic studies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.R. Ebeiling" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bonekey.2014.6" "Revista" => array:3 [ "tituloSerie" => "Bonekey Rep" "fecha" => "2014" "volumen" => "3" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0290" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D: a millennium perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.F. Holick" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jcb.10338" "Revista" => array:6 [ "tituloSerie" => "J Cell Biochem" "fecha" => "2003" "volumen" => "88" "paginaInicial" => "296" "paginaFinal" => "307" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12520530" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0295" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D and autoimmune rheumatologic disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.F. Pelajo" 1 => "J.M. Lopez-Benitez" 2 => "L.C. Miller" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autrev.2010.02.011" "Revista" => array:6 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2010" "volumen" => "9" "paginaInicial" => "507" "paginaFinal" => "510" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20146942" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0300" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Orbach" 1 => "G. Zandman-Goddard" 2 => "H. Amital" 3 => "V. Barak" 4 => "Z. Szekanecz" 5 => "G. Szucs" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1196/annals.1398.044" "Revista" => array:6 [ "tituloSerie" => "Ann N Y Acad Sci" "fecha" => "2007" "volumen" => "1109" "paginaInicial" => "385" "paginaFinal" => "400" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17785327" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0305" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D deficiency in lupus erythematosus: prevalence, predictors and clinical consequences" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G. Ruiz-Irastorza" 1 => "M.V. Egurbide" 2 => "N. Olivares" 3 => "A. Martinez-Beriotxoa" 4 => "C. Aguirre" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rheumatoloy" "fecha" => "2008" "volumen" => "47" "paginaInicial" => "920" "paginaFinal" => "923" "itemHostRev" => array:3 [ "pii" => "S0022534712042152" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0310" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Amital" 1 => "Z. Szekanecz" 2 => "G. Szücs" 3 => "K. Dankó" 4 => "E. Nagy" 5 => "T. Csépány" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2009.120329" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2010" "volumen" => "69" "paginaInicial" => "1155" "paginaFinal" => "1157" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20439290" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0315" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum 25-hydroxyvitamin D levels in patients with cutaneous lupus erythematosus in a Mediterranean region" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Cutillas-Marco" 1 => "M. Morales-Suarez-Varela" 2 => "A. Marquina-Vila" 3 => "W. Grant" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0961203309360807" "Revista" => array:6 [ "tituloSerie" => "Lupus" "fecha" => "2010" "volumen" => "19" "paginaInicial" => "810" "paginaFinal" => "814" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20305048" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0320" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D may not be a good marker of disease activity in Korean patients with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H.A. Kim" 1 => "J.M. Sung" 2 => "J.Y. Jeon" 3 => "J.M. Yoon" 4 => "C.H. Suh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00296-010-1442-1" "Revista" => array:7 [ "tituloSerie" => "Rheumatol Int" "fecha" => "2011" "volumen" => "31" "paginaInicial" => "1189" "paginaFinal" => "1194" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20352222" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534713035246" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0325" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The immunopathological role of vitamin D in patients with SLE: data from a single centre registry in Hungary" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P. Szodoray" 1 => "T. Tarr" 2 => "A. Bazso" 3 => "G. Poor" 4 => "G. Szegedi" 5 => "E. Kiss" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/03009742.2010.507220" "Revista" => array:7 [ "tituloSerie" => "Scand J Rheumatol" "fecha" => "2011" "volumen" => "40" "paginaInicial" => "122" "paginaFinal" => "126" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20977384" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534708015644" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0330" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D insufficiency in a large female SLE cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.M. Toloza" 1 => "D.E. Cole" 2 => "D.D. Gladman" 3 => "D. Ibañez" 4 => "M.B. Urowitz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0961203309345775" "Revista" => array:6 [ "tituloSerie" => "Lupus" "fecha" => "2010" "volumen" => "19" "paginaInicial" => "13" "paginaFinal" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19897520" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0335" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "25-Hydroxyvitamin D and cardiovascular risk factors in women with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.W. Wu" 1 => "E.Y. Rhew" 2 => "A.R. Dyer" 3 => "D.D. Dunlop" 4 => "C.B. Langman" 5 => "H. Price" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.24785" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2009" "volumen" => "61" "paginaInicial" => "1387" "paginaFinal" => "1395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19790113" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0340" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D deficiency in patients with active systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "V.Z. Borba" 1 => "J.G. Vieira" 2 => "T. Kasamatsu" 3 => "S.C. Radominski" 4 => "E.I. Sato" 5 => "M. Lazaretti-Castro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00198-008-0676-1" "Revista" => array:6 [ "tituloSerie" => "Osteoporos Int" "fecha" => "2009" "volumen" => "20" "paginaInicial" => "427" "paginaFinal" => "433" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18600287" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0345" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Photoprotective behaviour and sunscreen use: impact on vitamin D levels in cutaneous lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Cusack" 1 => "C. Danby" 2 => "J.C. Fallon" 3 => "W.L. Ho" 4 => "B. Murray" 5 => "J. Brady" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-0781.2008.00373.x" "Revista" => array:6 [ "tituloSerie" => "Photodermatol Photoimmunol Photomed" "fecha" => "2008" "volumen" => "24" "paginaInicial" => "260" "paginaFinal" => "267" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18811868" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0350" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisone-treated adolescents with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. O’Regan" 1 => "R.W. Chesney" 2 => "A. Hamstra" 3 => "J.A. Eisman" 4 => "A.M. O’Gorman" 5 => "H.F. Deluca" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Paediatr Scand" "fecha" => "1979" "volumen" => "68" "paginaInicial" => "109" "paginaFinal" => "111" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/214990" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0355" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.M. Huisman" 1 => "K.P. White" 2 => "A. Algra" 3 => "M. Harth" 4 => "R. Vieth" 5 => "J.W. Jacobs" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2001" "volumen" => "28" "paginaInicial" => "2535" "paginaFinal" => "2539" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11708429" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0360" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D3 in patients with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Müller" 1 => "N.J. Kriegbaum" 2 => "B. Baslund" 3 => "O.H. Sørensen" 4 => "M. Thymann" 5 => "K. Bentzen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "1995" "volumen" => "14" "paginaInicial" => "397" "paginaFinal" => "400" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7586974" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0365" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and predictors of vitamin D deficiency in non-supplemented women with systemic lupus erythematosus in the Mediterranean region: a cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Muñoz-Ortego" 1 => "V. Torrente-Segarra" 2 => "D. Prieto-Alhambra" 3 => "T.C. Salman-Monte" 4 => "J. Carbonell-Abello" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/03009742.2012.697189" "Revista" => array:7 [ "tituloSerie" => "Scand J Rheumatol" "fecha" => "2012" "volumen" => "41" "paginaInicial" => "472" "paginaFinal" => "475" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22830580" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534713036902" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0370" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bone health and systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Lee" 1 => "R. Ramsey-Goldman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Curr Rheumatol Rep" "fecha" => "2005" "volumen" => "7" "paginaInicial" => "482" "paginaFinal" => "489" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16303110" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0302283811000145" "estado" => "S300" "issn" => "03022838" ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0375" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and predictors of fragility fractures in systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.S. Yee" 1 => "N. Crabtree" 2 => "J. Skan" 3 => "N. Amft" 4 => "S. Bowman" 5 => "D. Situnayake" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2003.018127" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2005" "volumen" => "64" "paginaInicial" => "111" "paginaFinal" => "113" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15608308" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0380" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Redlich" 1 => "S. Ziegler" 2 => "H.P. Kiener" 3 => "S. Spitzauer" 4 => "P. Stohlawetz" 5 => "P. Bernecker" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2000" "volumen" => "59" "paginaInicial" => "308" "paginaFinal" => "310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10733481" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534710037778" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0385" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bone metabolism and bone mineral density of systemic lupus erythematosus at the time of diagnosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Teichmann" 1 => "U. Lange" 2 => "H. Stracke" 3 => "K. Federlin" 4 => "R.G. Bretzel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rheumatol Int" "fecha" => "1999" "volumen" => "18" "paginaInicial" => "137" "paginaFinal" => "140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10220833" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0390" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bone mineral density in systemic lupus erythematosus: comparison with rheumatoid arthritis and healthy controls" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "I. Gilboe" 1 => "T.K. Kvien" 2 => "G. Haugeberg" 3 => "G. Husby" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2000" "volumen" => "59" "paginaInicial" => "110" "paginaFinal" => "115" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10666165" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0395" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Three year followup of bone mineral density change in premenopausal women with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Y. Kipen" 1 => "E. Briganti" 2 => "B. Strauss" 3 => "R. Will" 4 => "G. Littlejohn" 5 => "E. Morand" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "1999" "volumen" => "26" "paginaInicial" => "310" "paginaFinal" => "317" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9972964" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0400" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Longitudinal analysis of bone mineral density in pre-menopausal female systemic lupus erythematosus patients: deleterious role of glucocorticoid therapy at the lumbar spine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D. Jardinet" 1 => "C. Lefèbvre" 2 => "G. Depresseux" 3 => "M. Lambert" 4 => "J.P. Devogelaer" 5 => "F.A. Houssiau" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2000" "volumen" => "39" "paginaInicial" => "389" "paginaFinal" => "392" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0405" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Six-year follow-up study of bone mineral density in patients with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Jacobs" 1 => "L.A. Korswagen" 2 => "A.M. Schilder" 3 => "L.H. van Tuyl" 4 => "B.A. Dijkmans" 5 => "W.F. Lems" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00198-012-2157-9" "Revista" => array:7 [ "tituloSerie" => "Osteoporos Int" "fecha" => "2013" "volumen" => "24" "paginaInicial" => "1827" "paginaFinal" => "1833" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23052940" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534709017650" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0410" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Frequency of fractures in women with systemic lupus erythematosus: comparison with United States population data" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Ramsey-Goldman" 1 => "J.E. Dunn" 2 => "C.F. Huang" 3 => "D. Dunlop" 4 => "J.E. Rairie" 5 => "S. Fitzgerald" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/1529-0131(199905)42:5<882::AID-ANR6>3.0.CO;2-C" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "1999" "volumen" => "42" "paginaInicial" => "882" "paginaFinal" => "890" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10323443" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0415" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The clinical significance of vitamin D in systemic lupus erythematosus: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Sakthiswary" 1 => "A.A. Raymond" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0055275" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "e55275" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23383135" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0420" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D: modulator of the immune system" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "F. Baeke" 1 => "T. Takiishi" 2 => "H. Korf" 3 => "C. Gysemans" 4 => "C. Mathieu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.coph.2010.04.001" "Revista" => array:7 [ "tituloSerie" => "Curr Opin Pharmacol" "fecha" => "2010" "volumen" => "10" "paginaInicial" => "482" "paginaFinal" => "496" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20427238" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0090429512008023" "estado" => "S300" "issn" => "00904295" ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0425" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.H. Costenbader" 1 => "D. Feskanich" 2 => "M. Holmes" 3 => "E.W. Karlson" 4 => "E. Benito-Garcia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2007.072736" "Revista" => array:7 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2008" "volumen" => "67" "paginaInicial" => "530" "paginaFinal" => "535" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17666449" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0090429508007826" "estado" => "S300" "issn" => "00904295" ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0430" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D in systemic lupus erythematosus: modest association with disease activity and the urine protein-to-creatinine ratio" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Petri" 1 => "K.J. Bello" 2 => "H. Fang" 3 => "L.S. Magder" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.37953" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2013" "volumen" => "65" "paginaInicial" => "1865" "paginaFinal" => "1871" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23553077" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0435" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D levels in Chinese patients with systemic lupus erythematosus: relationship with disease activity, vascular risk factors and atherosclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C.C. Mok" 1 => "D.J. Birmingham" 2 => "H.W. Leung" 3 => "L.A. Hebert" 4 => "H. Song" 5 => "B. Robin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/ker212" "Revista" => array:6 [ "tituloSerie" => "Rheumatology" "fecha" => "2012" "volumen" => "51" "paginaInicial" => "644" "paginaFinal" => "652" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21719424" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0440" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D levels and disease status in Texas patients with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Thudi" 1 => "S. Yin" 2 => "A.E. Wandstrat" 3 => "Q.Z. Li" 4 => "N.J. Olsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MAJ.0b013e318134eeb6" "Revista" => array:7 [ "tituloSerie" => "Am J Med Sci" "fecha" => "2008" "volumen" => "335" "paginaInicial" => "99" "paginaFinal" => "104" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18277116" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534709023556" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0445" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D deficiency: an important, common, and easily treatable cardiovascular risk factor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.H. Lee" 1 => "J.H. O’Keefe" 2 => "D. Bell" 3 => "D.D. Hensrud" 4 => "M.F. Holick" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2008.08.050" "Revista" => array:7 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2008" "volumen" => "52" "paginaInicial" => "1949" "paginaFinal" => "1956" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19055985" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534711033428" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0450" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "25-Hydroxyvitamin D and risk of myocardial infarction in men" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Giovannucci" 1 => "Y. Liu" 2 => "B.W. Hollis" 3 => "E.B. Rimm" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archinte.168.11.1174" "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2008" "volumen" => "168" "paginaInicial" => "1174" "paginaFinal" => "1180" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18541825" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0455" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D levels and early mortality among incident hemodialysis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Wolf" 1 => "A. Shah" 2 => "O. Gutierrez" 3 => "E. Ankers" 4 => "M. Monroy" 5 => "H. Tamez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.ki.5002451" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2007" "volumen" => "72" "paginaInicial" => "1004" "paginaFinal" => "1013" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17687259" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0460" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "25-Hydroxyvitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Reynolds" 1 => "S. Haque" 2 => "J.L. Berry" 3 => "P. Pemberton" 4 => "L.S. Teh" 5 => "P. Ho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/ker352" "Revista" => array:6 [ "tituloSerie" => "Rheumatology" "fecha" => "2012" "volumen" => "51" "paginaInicial" => "544" "paginaFinal" => "551" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22120462" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0465" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.L. Ravenell" 1 => "D.L. Kamen" 2 => "J.D. Spence" 3 => "B.W. Hollis" 4 => "T.J. Fleury" 5 => "M.G. Janech" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MAJ.0b013e31823fa7d9" "Revista" => array:6 [ "tituloSerie" => "Am J Med Sci" "fecha" => "2012" "volumen" => "344" "paginaInicial" => "268" "paginaFinal" => "273" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22222338" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0470" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D deficiency does not predict progression of coronary artery calcium, carotid intima-media thickness or high-sensitivity C-reactive protein in systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.N. Kiani" 1 => "H. Fang" 2 => "L.S. Magder" 3 => "M. Petri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/ket271" "Revista" => array:6 [ "tituloSerie" => "Rheumatology" "fecha" => "2013" "volumen" => "52" "paginaInicial" => "2071" "paginaFinal" => "2076" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23955647" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0475" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Are calcium and vitamin D supplements for everyone?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.A. García Vadillo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.reuma.2011.04.008" "Revista" => array:7 [ "tituloSerie" => "Pro Reumatol Clin" "fecha" => "2011" "volumen" => "2" "numero" => "Suppl." "paginaInicial" => "S34" "paginaFinal" => "S39" "itemHostRev" => array:3 [ "pii" => "S0022534711035452" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0480" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. Autier" 1 => "S. Gandini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archinte.167.16.1730" "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2007" "volumen" => "167" "paginaInicial" => "1730" "paginaFinal" => "1737" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17846391" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0485" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Abou-Raya" 1 => "S. Abou-Raya" 2 => "M. Helmii" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.111594" "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2013" "volumen" => "40" "paginaInicial" => "265" "paginaFinal" => "272" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23204220" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0490" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevention of immunological disorders in MRL//lpr mice by a new synthetic analogue of vitamin D3 22oxa-1 alpha, 25 dihydroxyvitamin D3" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Abe" 1 => "K. Nakamura" 2 => "Y. Takita" 3 => "T. Xlakano" 4 => "H. Irie" 5 => "Y. Nishii" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Nutr Sci Vitaminol" "fecha" => "1990" "volumen" => "36" "paginaInicial" => "21" "paginaFinal" => "31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2163440" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001100000004/v1_201507020119/S2173574314001804/v1_201507020119/en/main.assets" "Apartado" => array:4 [ "identificador" => "8383" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001100000004/v1_201507020119/S2173574314001804/v1_201507020119/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574314001804?idApp=UINPBA00004M" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 17 | 17 | 34 |
| 2024 October | 75 | 28 | 103 |
| 2024 September | 91 | 22 | 113 |
| 2024 August | 127 | 37 | 164 |
| 2024 July | 157 | 26 | 183 |
| 2024 June | 150 | 33 | 183 |
| 2024 May | 162 | 30 | 192 |
| 2024 April | 120 | 26 | 146 |
| 2024 March | 145 | 28 | 173 |
| 2024 February | 69 | 22 | 91 |
| 2024 January | 115 | 24 | 139 |
| 2023 December | 79 | 23 | 102 |
| 2023 November | 150 | 34 | 184 |
| 2023 October | 265 | 29 | 294 |
| 2023 September | 165 | 26 | 191 |
| 2023 August | 100 | 14 | 114 |
| 2023 July | 95 | 29 | 124 |
| 2023 June | 102 | 29 | 131 |
| 2023 May | 102 | 22 | 124 |
| 2023 April | 81 | 15 | 96 |
| 2023 March | 184 | 23 | 207 |
| 2023 February | 143 | 31 | 174 |
| 2023 January | 138 | 17 | 155 |
| 2022 December | 157 | 29 | 186 |
| 2022 November | 148 | 26 | 174 |
| 2022 October | 178 | 22 | 200 |
| 2022 September | 119 | 36 | 155 |
| 2022 August | 150 | 48 | 198 |
| 2022 July | 155 | 38 | 193 |
| 2022 June | 150 | 45 | 195 |
| 2022 May | 208 | 39 | 247 |
| 2022 April | 283 | 52 | 335 |
| 2022 March | 210 | 53 | 263 |
| 2022 February | 177 | 39 | 216 |
| 2022 January | 166 | 39 | 205 |
| 2021 December | 132 | 41 | 173 |
| 2021 November | 113 | 50 | 163 |
| 2021 October | 111 | 60 | 171 |
| 2021 September | 116 | 50 | 166 |
| 2021 August | 80 | 35 | 115 |
| 2021 July | 93 | 33 | 126 |
| 2021 June | 203 | 34 | 237 |
| 2021 May | 181 | 44 | 225 |
| 2021 April | 675 | 98 | 773 |
| 2021 March | 190 | 42 | 232 |
| 2021 February | 145 | 31 | 176 |
| 2021 January | 107 | 29 | 136 |
| 2020 December | 89 | 28 | 117 |
| 2020 November | 90 | 30 | 120 |
| 2020 October | 77 | 21 | 98 |
| 2020 September | 98 | 38 | 136 |
| 2020 August | 77 | 21 | 98 |
| 2020 July | 63 | 21 | 84 |
| 2020 June | 78 | 34 | 112 |
| 2020 May | 87 | 26 | 113 |
| 2020 April | 112 | 34 | 146 |
| 2020 March | 90 | 6 | 96 |
| 2020 February | 1 | 0 | 1 |
| 2018 May | 2 | 1 | 3 |
| 2018 April | 185 | 8 | 193 |
| 2018 March | 83 | 12 | 95 |
| 2018 February | 48 | 6 | 54 |
| 2018 January | 33 | 4 | 37 |
| 2017 December | 31 | 9 | 40 |
| 2017 November | 48 | 8 | 56 |
| 2017 October | 34 | 14 | 48 |
| 2017 September | 34 | 15 | 49 |
| 2017 August | 28 | 8 | 36 |
| 2017 July | 38 | 15 | 53 |
| 2017 June | 71 | 12 | 83 |
| 2017 May | 74 | 19 | 93 |
| 2017 April | 51 | 20 | 71 |
| 2017 March | 42 | 13 | 55 |
| 2017 February | 35 | 16 | 51 |
| 2017 January | 47 | 7 | 54 |
| 2016 December | 63 | 23 | 86 |
| 2016 November | 65 | 16 | 81 |
| 2016 October | 102 | 20 | 122 |
| 2016 September | 102 | 19 | 121 |
| 2016 August | 66 | 8 | 74 |
| 2016 July | 39 | 11 | 50 |
| 2015 December | 2 | 0 | 2 |
| 2015 November | 1 | 25 | 26 |
| 2015 October | 3 | 36 | 39 |
| 2015 September | 4 | 0 | 4 |
| 2015 August | 5 | 47 | 52 |
| 2015 July | 49 | 21 | 70 |
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