Prevalence of Vitamin D Deficiency in Patients Treated for Juvenile Idiopathic Arthritis and Potential Role of Methotrexate: A Preliminary Study

Background: Vitamin D deficiency is reported in rheumatological diseases in adults. The aim was to evaluate the prevalence of vitamin D deficiency in children with juvenile idiopathic arthritis (JIA) and to investigate potential correlations between vitamin D status and clinical factors, laboratory traits, and medical treatment, including methotrexate (MTX) and glucocorticoids (GCs). Methods: In 189 patients aged 3–17.7 years, with JIA in the stable stage of the disease, anthropometry, clinical status, serum 25-hydroxyvitamin D [25(OH)D], calcium (Ca), phosphate (PO₄), total alkaline phosphatase (ALP), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed. Results: Median 25(OH)D level was 15.00 ng/mL, interquartile range (IQR) 12.00 ng/mL. Vitamin D deficiency was found in 67.2% and was independent of sex, disease manifestation, and CRP, ESR, ALP, or PO₄ levels. Higher doses of MTX corresponded with lower 25(OH)D levels using both univariate and multivariate models (p < 0.05). No such trend was found for GCs treatment. Serum Ca was lower in patients treated with GCs (p = 0.004), MTX (p = 0.03), and combined GCs/MTX (p = 0.034). Conclusions: JIA patients are vitamin D depleted independently of disease activity or inflammatory markers. MTX therapy may be an iatrogenic factor leading to inadequate 25(OH)D levels. Vitamin D supplementation should be considered in all children with JIA, particularly those receiving long-term MTX therapy.     

The role of vitamins in the prevention of osteoporosis--a brief status report.

This papers summarizes the main role vitamins are believed to play in the prevention of osteoporosis, a common disease which is anticipated to rapidly increase because of the aging of the population. Vitamin D, the classical vitamin related to bone health, improves bone strength mainly by increasing intestinal calcium absorption and reabsorption of calcium by the kidney. Several intervention studies demonstrated in humans that vitamin D can improve bone status as measured by bone density. Vitamin C is considered an essential cofactor of collagen formation. Epidemiological studies report a positive association between vitamin C intake and bone density. Intervention studies on the effect of vitamin C on bone status are missing. Vitamin B6 could function as a cofactor to build up cross-links. In humans, however, there is little evidence to support this. Vitamin K is required for the biological activity of several coagulation factors; the classical function of vitamin K. Recent research also points to a role of vitamin K in bone metabolism. Vitamin K mediates the <--carboxylation of glutamyl residues on several bone proteins, notably osteocalcin. Epidemiological studies and results from first intervention trials are consistently suggesting that vitamin K may improve bone health.     

维生素D与脑发育相关研究进展

近年来有关维生素D研究进展迅速,其中维生素D与大脑的发育之间的关系日益受到关注。维生素D是一种具有类固醇激素作用的物质,可参与调节细胞増殖、分化及凋亡,大量研究表明,维生素D除了具有促进钙磷吸收、骨骼发育及发挥免疫调节的作用,还可作为一类神经激素影响神经系统的发育和功能,本文将从大脑中的维生素D及维生素D受体、维生素D对脑发育可能的调控作用及维生素D与儿童神经精神障碍疾病的相关性等几方面进行阐述。     

25-Hydroxyvitamin D and functional outcomes in adolescents

Vitamin D is essential for bone growth and development in children and adolescents. Adolescence is a crucial phase in bone development. Cross-sectional studies have shown a relation between vitamin D status and bone mineral density in adolescents. Long-term supplementation studies have supported the importance of vitamin D for bone health in adolescence. However, we need more studies on the optimal serum 25-hydroxyvitamin D concentration and the optimal vitamin D dosage for bone health in this age group. In addition, we need to evaluate the best way to increase vitamin D status in the general public from a public health point of view.     

Vitamin D Interactions with Soy Isoflavones on Bone after Menopause: A Review

Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor β and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women.     

Effects of Vitamin D on Fertility,Pregnancy and Polycystic Ovary Syndrome—A Review

Polycystic ovary syndrome (PCOS) is one of the most common endocrine reproductive disorders in women. Vitamin D deficiency is also quite common in this condition. The degree of vitamin D deficiency correlates with the severity of PCOS. Both male and female vitamin D levels play a role in fertility and affect the outcomes of in vitro fertilization (IVF). Moreover, fertility and IVF indicators are improved by vitamin D not only in healthy women but in those diagnosed with PCOS. Both vitamin D deficiency and PCOS increase pregnancy-related complications. Vitamin D supplementation and optimal vitamin D levels decrease both maternal and fetal risk for complications and adverse events. Furthermore, vitamin D supplementation may ameliorate or even prevent pregnancy-related reversible bone loss in mothers. This review emphasizes the roles of vitamin D deficiency and vitamin D supplementation and their correlation with PCOS regarding reproductive health.     

Vitamin D and bone health: potential mechanisms

Osteoporosis is associated with increased morbidity, mortality and significant economic and health costs. Vitamin D is a secosteriod hormone essential for calcium absorption and bone mineralization which is positively associated with bone mineral density [BMD]. It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. Sub-optimal vitamin D status has been reported in many populations but it is a particular concern in older people; thus there is clearly a need for effective strategies to optimise bone health. A number of recent studies have suggested that the role of vitamin D in preventing fractures may be via its mediating effects on muscle function (a defect in muscle function is one of the classical signs of rickets) and inflammation. Studies have demonstrated that vitamin D supplementation can improve muscle strength which in turn contributes to a decrease in incidence of falls, one of the largest contributors to fracture incidence. Osteoporosis is often considered to be an inflammatory condition and pro-inflammatory cytokines have been associated with increased bone metabolism. The immunoregulatory mechanisms of vitamin D may thus modulate the effect of these cytokines on bone health and subsequent fracture risk. Vitamin D, therefore, may influence fracture risk via a number of different mechanisms.     

维生素D缺乏与儿童疾病表观遗传学研究

维生素D不仅对骨代谢有着经典的作用,同时在免疫、细胞增殖和分化中有重要的作用。最近的研究发现,孕期维生素D水平也可能通过表观遗传修饰影响到后代儿童期非骨骼系统疾病的易感性,如哮喘,自身免疫性疾病和神经精神疾病等。本文将综述维生素D缺乏与儿童疾病表观遗传学的研究进展。     

Vitamin d and rehabilitation: improving functional outcomes.

Vitamin D inadequacy is pandemic among rehabilitation patients in both inpatient and outpatient settings. Male and female patients of all ages and ethnic backgrounds are affected. Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes the painful bone disease osteomalacia, and worsens proximal muscle strength and postural sway. Vitamin D inadequacy can be prevented by sensible sun exposure and adequate dietary intake with supplementation. Vitamin D status is determined by measurement of serum 25-hydroxyvitamin D. The recommended healthful serum level is between 30 and 60 ng/mL. 25-Hydroxyvitamin D levels of >30 ng/mL are sufficient to suppress parathyroid hormone production and to maximize the efficiency of dietary calcium absorption from the small intestine. This can be accomplished by ingesting 1000 IU of vitamin D(3) per day, or by taking 50,000 IU of vitamin D(2) every 2 weeks. Vitamin D toxicity is observed when 25-hydroxyvitamin D levels exceed 150 ng/mL. Identification and treatment of vitamin D deficiency reduces the risk of vertebral and nonvertebral fractures by improving bone health and musculoskeletal function. Vitamin D deficiency and osteomalacia should be considered in the differential diagnosis of patients with musculoskeletal pain, fibromyalgia, chronic fatigue syndrome, or myositis. There is a need for better education of health professionals and the general public regarding the optimization of vitamin D status in the care of rehabilitation patients.     

Vitamin D and respiratory infection in adults

Vitamin D insufficiency is a global issue that has significant implications for health. The classical role of vitamin D in bone mineralisation is well known; vitamin D deficiency leads to rickets, osteomalacia or osteoporosis. The role of vitamin D in an immune system is less known. Vitamin D is not an actual vitamin but a secosteroid hormone produced in the skin from 7-dehydrocholesterol after exposure to sunlight UVB radiation. Nutrition and supplements are main sources of vitamin D in wintertime in northern countries as sunlight exposure is inadequate for the production. For activation vitamin D needs to be hydroxylated in liver to form 25-hydroxyvitamin D and in kidney to 1,25-dihydroxyvitamin D, the most active hormone in Ca absorption in the gut. For determination of vitamin D status serum 25-hydroxyvitamin D level, the major circulating form of the hormone is to be measured. Vitamin D regulates gene expression through binding with vitamin D receptors, which dimerises with retinoid X receptor. This complex binds to vitamin D-responsive elements inside the promoter regions of vitamin D-responsive genes. Vitamin D has a key role in innate immunity activation; the production of antimicrobial peptides (cathelicidin and defensins) following Toll-like receptor stimulation by pathogen lipopeptides is dependent on sufficient level of 25-hydroxyvitamin D. Clinically, there is evidence of the association of vitamin D insufficiency and respiratory tract infections. There is also some evidence of the prevention of infections by vitamin D supplementation. Randomised controlled trials are warranted to explore this preventive effect.     

Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice

Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association.     

The vitamin D epidemic and its health consequences

Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.     

Validation of a dietary vitamin D questionnaire using multiple diet records and the block 98 health habits and history questionnaire in healthy postmenopausal women in northern California

Vitamin D deficiency is common in older women and can negatively impact bone status. A simple method by which clinicians and researchers can evaluate a patient's vitamin D dietary intake could help identify individuals at risk for vitamin D deficiency. This study was done to validate a short dietary vitamin D questionnaire. Postmenopausal women (n=122), with a mean age of 63.9 ± 7.8 years, completed a Brief Vitamin D Questionnaire (BVDQ), the Block Health History and Habits Questionnaire 1998 (BHHHQ98), a 3-day food record, and an evaluation of serum 25 hydroxyvitamin D (25[OH]D) levels. Data were analyzed using Pearson correlation coefficients, Wilcoxon signed ranks tests, and Bland-Altman analyses to compare the performance of the BVDQ to the BHHHQ98 and to the diet record. As assessed by the BVDQ, vitamin D intake averaged 178.7 ± 112.3 IU per day, correlating well with the Block HHHQ98 (r=0.51, P<0.001) and the 3-day food record (r=0.43, P<0.001). Compared with the food record, both the BVDQ and the BHHHQ98 overestimated dietary vitamin D intake by less than 100 IU/day. The two questionnaires performed nearly identically at all levels of vitamin D intake. Serum 25(OH)D was not related to vitamin D intake as measured by either the BVDQ or the BHHHQ98, but did correlate weakly with vitamin D intake from the 3-day diet record (r=0.20, P=0.04). The Brief Vitamin D Questionnaire correlated well with the longer and more intense dietary assessment methods, making it a simple and accurate instrument for assessing vitamin D intake.     

Vitamin D status: effects on quality of life in osteoporosis among Turkish women

Background and objectives Vitamin D deficiency causes muscle weakness, impairs bone formation and neuromuscular coordination thus leading to an increase in fracture risk. It has been found that inadequate levels of vitamin D are present in most of the osteoporosis patients. However, very few studies investigate the association between vitamin D status and quality of life (QOL). The aim of this study is to investigate the effects of vitamin D on QOL among Turkish women with osteoporosis. Methods 259 patients (61.0 ± 8.9 years) with osteoporosis were evaluated by physical activity level, back pain, bone turnover markers, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone levels and bone mineral density. QOL was assessed using QOL Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). 25(OH)D levels below 20 ng/ml was defined as vitamin D insufficiency, below 12 ng/ml as vitamin D deficiency. Results Mean 25(OH)D level was 22.7 ± 12.6 ng/ml and mean total QUALEFFO score was 43.3 ± 14.9. Vitamin D levels were significantly correlated with all subscales and total score of QUALEFFO (r = −0.25, P = 0.0001). Vitamin D insufficiency was determined in 132 patients (51%). In vitamin D deficient (<12 ng/ml) group all subscales and total QOL were found to be poorer when compared with the groups whose vitamin D levels were ≥12 and <20 ng/ml and ≥20 ng/ml (effect sizes 0.41 and 0.62 respectively, P = 0.0001 for total QOL). Vitamin D level, education, concomitant diseases, physical activity level and pain severity were found to be significantly associated with QOL in multiple linear regression analysis model. Conclusions Vitamin D insufficiency affects physical, social and mental functions of osteoporosis patients and impairs QOL. Vitamin D was found to be one of the factors affecting QOL.     

Supplementation with vitamin D and calcium in long-term care residents

Vitamin D deficiency is a common finding in institutionalized older persons. Vitamin D-deficient elderly persons are at higher risk of falls and fractures. Long-term care residents should be considered at high risk of vitamin D deficiency and therefore vitamin D supplementation is highly recommended in this population. The minimal effective dose is 800 IU per day. It is recommended that vitamin D supplementation should be implemented in all patients in residential aged care facilities. In addition to vitamin D, calcium supplementation has shown to enhance the effect of vitamin D on bone. Calcium intake should be optimized (1200-1500 mg per day recommended) and supplementation offered to those with inadequate intake. The addition of calcium depends on tolerance, history of kidney stones, and emerging data regarding its cardiovascular safety.     

Bone resorption activity of all-trans retinoic acid is independent of vitamin D in rats

The mechanism by which all-trans retinoic acid (ATRA) induces bone resorption is unknown. However, an interaction between vitamin A and vitamin D has been established. In fact, although the mechanism is still unclear, vitamin A has been shown to be a weak antagonist of the actions of vitamin D. Taking into account this interaction and the influence of vitamin D on other calcitropic hormones, such as parathyroid hormone, the effect of vitamin D on ATRA-induced bone resorption was investigated. Vitamin D-deficient rats were fed diets containing 0 or 150 micro g of ATRA/g of diet. The rats then were orally administered 0 or 625 ng of cholecalciferol (vitamin D(3)) daily. Various bone parameters were measured after 3-8 wk. Regardless of the presence or absence of vitamin D(3), ATRA was able to cause bone resorption. In addition to examining the effect of vitamin D on ATRA-induced bone resorption under normal conditions, this effect also was studied under conditions that inhibit bone mineralization or growth by altering dietary calcium (Ca) and phosphorus (P) levels. Changes in dietary levels of Ca and P did not affect the ability of ATRA to cause bone resorption. Interestingly, despite its ability to stimulate bone resorption, ATRA did not affect serum calcium or phosphorus levels. Overall, the ability of ATRA to cause bone resorption is not dependent on vitamin D(3), dietary Ca or dietary P.     

Vitamin D: the light side of sunshine

Under normal circumstances, vitamin D is mainly obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of ingested calcium (and phosphate). This assists in building bone at younger ages and ensures that despite obligatory urinary losses, bone does not need to be resorbed to maintain blood calcium concentrations. Vitamin D compounds appear to have direct effects to improve bone and muscle function, and there is good, although not entirely consistent, evidence that supplemental vitamin D and calcium together reduce falls and fractures in older individuals. On the basis of calcium control and musculoskeletal function, target levels for 25OHD in blood are at least 50-60?nmol/l and there may be a case for higher targets of 75-80?nmol/l. There are vitamin D receptors in most nucleated cells and some evidence, although not consistent, that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality and increase insulin responsiveness. Vitamin D levels are maintained better in the presence of adequate calcium intakes, more exercise and less obesity. Genetic variation may have an effect on vitamin D blood levels and response to treatment with vitamin D.     

Vitamin D Deficiency in Older Patients—Problems of Sarcopenia,Drug Interactions,Management in Deficiency

Vitamin D deficiency frequently occurs in older people, especially in individuals with comorbidity and polypharmacotherapy. In this group, low vitamin D plasma concentration is related to osteoporosis, osteomalacia, sarcopenia and myalgia. Vitamin D levels in humans is an effect of the joint interaction of all vitamin D metabolic pathways. Therefore, all factors interfering with individual metabolic stages may affect 25-hydroxyvitamin D plasma concentration. The known factors affecting vitamin D metabolism interfere with cytochrome CYP3A4 activity. There is another group of factors that impairs intestinal vitamin D absorption. The phenomenon of drugs and vitamin D interactions is observed first and foremost in patients with comorbidity. This is a typical situation, where the absence of “hard evidence” is not synonymous with the possible lack of adverse effects. Osteoporosis and sarcopenia (generalized and progressive decrease of skeletal muscle mass and strength) are some of the musculoskeletal consequences of hypovitaminosis D. These consequences are related to an increased risk of adverse outcomes, including bone fractures, physical disabilities, and a lower quality of life. This can lead not only to an increased risk of falls and fractures but is also one of the main causes of frailty syndrome in the aging population. Generally, Vitamin D plasma concentration is significantly lower in subjects with osteoporosis and muscle deterioration. In some observational and uncontrolled treatment studies, vitamin D supplementation resulted in a reduction of proximal myopathy and muscle pain. The most conclusive results were found in subjects with severe vitamin D deficiency and in patients avoiding large doses of vitamin D. However, the role of vitamin D in muscle pathologies is not clear and research has provided conflicting results. This is plausibly due to the heterogeneity of the subjects, vitamin D doses and environmental factors. This report presents data on some problems with vitamin D deficiency in the elderly population and the management of vitamin D deficiency D in successful or unsuccessful aging.     

Nutritional determinants of bone health

Osteoporosis is a major public health problem. The aging population will require vigilant prevention, education, and treatment to maintain bone density and reduce the risk of fractures and falls. Nutritional requirements of elderly persons can have a profound effect on bone health. Calcium, vitamin D, and protein are vital nutrients for optimal bone health. Adequate calcium is essential for bone maintenance. Vitamin D research shows a link between reduced falls and fractures. Related macro- and micronutrients play an important role in bone mass integrity and quality. Adequate nutrition for older adults needs to be encouraged to promote and maintain bone health.     

Vitamin D and bone health in postmenopausal women

Osteoporosis, a disease of increased skeletal fragility, is becoming increasingly common as the U.S. population ages. Adequate vitamin D and calcium intake is the cornerstone of osteoporosis prevention and treatment. Age-related changes in vitamin D and calcium metabolism increase the risk of vitamin D insufficiency and secondary hyperparathyroidism. Although longitudinal data have suggested a role of vitamin D intake in modulating bone loss in perimenopausal women, studies of vitamin D and calcium supplementation have failed to support a significant effect of vitamin D and calcium during early menopause. There is a clearer benefit in vitamin D and calcium supplementation in older postmenopausal women. Vitamin D intake between 500 and 800 IU daily, with or without calcium supplementation, has been shown to increase bone mineral density (BMD) in women with a mean age of approximately 63 years. In women older than 65, there is even more benefit with vitamin D intakes of between 800 and 900 IU daily and 1200-1300 mg of calcium daily, with increased bone density, decreased bone turnover, and decreased nonvertebral fractures. The decreases in nonvertebral fractures may also be influenced by vitamin D-mediated decreases in body sway and fall risk. There are insufficient available data supporting a benefit from vitamin D supplementation alone, without calcium, to prevent osteoporotic fracture in postmenopausal women.