Vitamin D in Fracture Prevention and Muscle Function and Fall Prevention

This chapter reviews the potential of vitamin D for the prevention of falls and fractures. Evidence from randomized-controlled trials will be reviewed for both endpoints, as well as epidemiologic data that links higher 25-hydroxyvitamin D (25(OH)D) status to better bone and muscle health. The chapter addresses the evidence of fracture and fall prevention by dose of vitamin D, by type of dwelling and treatment duration. All data considered, this chapter summarizes the compelling dual benefit of vitamin D on fracture reduction by its bone and muscle target, a concept that is reviewed at the onset of the chapter.     

Wirkung von Vitamin D auf die Muskulatur im Rahmen der Osteoporose

A successful prevention strategy for fractures in the elderly should not be limited to an improvement in bone mineral density. Equally important is the prevention of falls. Thus, 90% of fractures in the elderly are associated with a fall and 30% of all ambulatory, and 50% of institutionalized elderly age 65 years and older fall at least once a year. Fall incidence increases 10% per decade thereafter. According to recent studies, vitamin D and calcium supplementation may be a promising treatment strategy targeting both bone mineral density, as well as muscle strength and the risk of falling. The protective effect of vitamin D on fractures has been attributed to the established moderate benefit of vitamin D on bone mineral density. However, an alternative explanation might be that vitamin D affects factors directly related to muscle strength, thus, reducing fracture risk through improved function and fall prevention, in addition to its benefits on calcium homeostasis.     

Use of vitamin D supplements and vitamin D status in patients taking bisphosphonate drugs

SIR, Bisphosphonate drugs are widely used to treat and preventosteoporosis. Following recent guidance from the National Institutefor Clinical Excellence (NICE) on secondary fracture prevention[1], it is likely that bisphosphonate use will increase, particularlyin older women. In the case of etidronate, the benefit of treatmentmay be attenuated by concomitant vitamin D deficiency [2]. Intrials demonstrating fracture reduction with modern bisphosphonates,such as risedronate and alendronate, it was ensured that subjectswere replete in calcium and vitamin D, so the effects of concomitantvitamin D deficiency are unknown. In order     

Vitamin D deficiency in children and adolescents: Epidemiology,impact and treatment

Vitamin D deficiency is highly prevalent among children and adolescents worldwide. The high rates of vitamin D deficiency during childhood are of major public health relevance, given the growing evidence that vitamin D deficiency may play a key role in the pathophysiology of many chronic diseases beyond rickets, including autoimmune conditions, cardiovascular diseases, and cancer. Identification, treatment, and prevention of vitamin D deficiency in childhood may therefore have profound health effects throughout the life span. In this review, we discuss the definitions, epidemiology, clinical implications, and treatment of vitamin D deficiency in children and adolescents.     

Vitamin D,Immunity and Human Disease

There is now increasing evidence that a key feature of vitamin D physiology is its ability to act as modulator of innate and adaptive immunity. This article will review the effects of vitamin D on innate immune responses with specific emphasis on the autocrine induction of antibacterial responses in macrophages, and the regulation of dendritic cell-mediated antigen presentation. The impact of vitamin D on adaptive immunity will also be reviewed, focusing on the effects of vitamin D on T-cell function, particularly the induction of regulatory T-cells. The review will also explore the impact of vitamin D deficiency on these facets of immune function, as well as the possible benefits of vitamin D supplementation. Finally, the review will also include an appraisal of human diseases such as infection and autoimmune disease that may be substantially influenced by vitamin D-dependent regulation of human immunity.     

Hypothesis: Correction of low vitamin D status among Arab women will prevent heart failure and improve cardiac function in established heart failure

Vitamin D deficiency is common in Arab countries particularly among women. This is the result of a low dietary intake of the vitamin, limited exposure to sunlight (a paradox in view of the high sunshine figures), skin colour, obesity and high parity. Apart from its adverse effects on bone in women and their offspring, vitamin D deficiency has the potential to cause or exacerbate heart failure through a number of mechanisms including activation of the renin-angiotensin system and increased arterial pressure. Accordingly, we propose that ensuring adequate vitamin D levels in Arab women will have a much greater impact on health than just the prevention of bone disease. In particular, we suggest that prevention and correction of vitamin D deficiency will reduce the incidence of heart failure and, for Arab women with established heart failure and vitamin D deficiency, improve cardiac function.     

Relative value of plain vitamin D and of biologically active vitamin D in the prevention and treatment of osteoporosis

Vitamin D metabolism has an important role in the pathogenesis of osteoporosis. Vitamin D deficiency is very common in elderly people in central Europe. This leads to secondary hyperparathyroidism and to increased bone resorption, resulting in osteoporosis. Combined with the elevated risk of falling that results from vitamin D deficiency, this increases the frequency of bone fractures. Severe vitamin D deficiency also causes impaired bone mineralization (osteomalacia). Controlled intervention trials with native vitamin D (and calcium) yielded no consistent results in terms of the prevention of extravertebral fractures. It appears likely that treatment with plain vitamin D is effective only in populations with vitamin D deficiency. Treatment with active vitamin D (1-alpha-hydroxylated metabolites such as alfacalcidol) has to be considered a pharmacological intervention that exerts pleiotropic effects on the gut (calcium absorption), bone (stimulation of formation), muscle (decreasing of the risk of falling), and immune system. Target groups are patients with disturbed vitamin D metabolism (renal insufficiency, glucocorticoid therapy, inflammatory disease such as rheumatoid arthritis). Alfacalcidol can prevent glucocorticoid-induced bone loss (high-grade evidence). In comparative studies alfacalcidol was superior to plain vitamin D.     

Nutritional rickets

Nutritional rickets (NR) is still the most common form of growing bone disease despite the efforts of health care providers to reduce the incidence of the disease. Today, it is well known that the etiology of NR ranges from isolated vitamin D deficiency (VDD) to isolated calcium deficiency. In Turkey, almost all NR cases result from VDD. Recent evidence suggests that in addition to its short- or long-term effects on skeletal development, VDD during infancy may predispose the patient to diseases such as diabetes mellitus, cancer and multiple sclerosis. Among the factors responsible for the high prevalence of VDD in developing countries and its resurgence in developed countries is limited sunshine exposure due to individuals' spending more time indoors (watching television and working on computer) or avoiding sun exposure intentionally for fear of skin cancer. Traditional clothing (covering the entire body except the face and hands) further limits the exposure time to sunlight and, thus, decreases the endogenous synthesis of vitamin D. In Turkey, maternal VDD and exclusive breastfeeding without supplementation were reported to be the most prominent reasons leading to NR. The diagnosis of NR is established by a thorough history and physical examination and confirmed by laboratory evaluation. Recent reports draw attention to the supplemental doses of vitamin D required to achieve a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/l) - the serum concentration that is needed to optimize absorption of dietary calcium and to suppress excessive secretion of parathyroid hormone. This type of prevention will also reduce fracture risk as well as prevent long-term negative effect of vitamin D insufficiency.     

Vitamin D deficiency: Implications for acute care in the elderly and in patients with chronic illness

There is evidence that the vast majority of hospitalized patients have vitamin D deficiency. Vitamin D deficiency is a poorly recognized pandemic with evidence to indicate inadequate testing and monitoring of response to treatment in high‐risk populations. Vitamin D receptors are ubiquitous in the human body and while the endocrine effects of vitamin D are well recognized, the autocrine and paracrine effects of this steroid hormone are less well appreciated. These functions include antimicrobial and immunomodulation effects as well benefits on cardiovascular health, autoimmune disease, cancer and metabolism. Vitamin D deficiency increases mortality and even a modest amount of vitamin D may enhance longevity. Emerging evidence suggests that a vitamin D replete state carries significant health benefits in acute illness. In this review, we discuss the role of vitamin D deficiency and potential benefits in treating this deficiency focusing on the implications for managing acute illness in elderly patients and those with an underlying chronic illness. Geriatr Gerontol Int 2011; 11: 395–407.     

The genes related to the effects of vitamin D on muscle and bone

Vitamin D is most frequently used as a drug for osteoporosis in Japan, and its effects on the maintenance of bone mineral density and inhibition of fracture risk have been shown. Recently, the actions of vitamin D on muscle have been elaborated, and its prevention of falls is noted. Active vitamin D modulates several genes in muscle and bones. The studies using vitamin D receptor deletion mice revealed that active vitamin D modulates the genes related to muscle differentiation and bone resorption.     

Effects of vitamin D in skeletal muscle: falls,strength, athletic performance and insulin sensitivity

Accompanying the high rates of vitamin D deficiency observed in many countries, there is increasing interest in the physiological functions of vitamin D. Vitamin D is recognized to exert extra‐skeletal actions in addition to its classic roles in bone and mineral homeostasis. Here, we review the evidence for vitamin D's actions in muscle on the basis of observational studies, clinical trials and basic research. Numerous observational studies link vitamin D deficiency with muscle weakness and sarcopaenia. Randomized trials predominantly support an effect of vitamin D supplementation and the prevention of falls in older or institutionalized patients. Studies have also examined the effect of vitamin D in athletic performance, both inferentially by UV radiation and directly by vitamin D supplementation. Effects of vitamin D in muscle metabolic function, specifically insulin sensitivity, are also addressed in this review. At a mechanistic level, animal studies have evaluated the roles of vitamin D and associated minerals, calcium and phosphate, in muscle function. In vitro studies have identified molecular pathways by which vitamin D regulates muscle cell signalling and gene expression. This review evaluates evidence for the various roles of vitamin D in skeletal muscle and discusses controversies that have made this a dynamic field of research.     

Clinical aspects of vitamin D in the management of rheumatoid arthritis

There is an increasing interest in the role of vitamin D as a potential treatment for a number of disparate diseases. In addition to its role in calcium homeostasis, vitamin D has a plethora of effects including immunomodulation, pleiotropic effects, modulating propensity to infection and blood pressure regulation. Detection and treatment of vitamin D deficiency in selected patients with RA is relevant as deficiency is common. Vitamin D therapy may modify the increased risk of falls and fracture in this group, and possibly exert additional immunomodulatory effects on disease onset and activity although data are largely epidemiological. Currently, there is no consensus view on vitamin D replacement regimens, nor an agreed optimal level of serum 25-hydroxyvitamin D [25(OH)D] for health. Indeed levels may vary for different organ systems and the concept of 'tissue specific vitamin D deficiency' needs to be considered. Therefore, there is clinical uncertainty regarding both when and how to correct vitamin D deficiency. Older patients, particularly post-menopausal women, and others at high risk of vitamin D deficiency should be preferentially targeted since they are likely to benefit most from supplementation. Clinicians should be aware of the technical difficulties associated with measuring and interpreting 25(OH)D levels. The administration of high-dose vitamin D as an oral weekly bolus is safe and can rapidly correct vitamin D deficiency followed by regular lower doses to maintain adequate levels.     

Vitamin D concentrations among people aged 65 years and over living in private households and institutions in England: population survey

BACKGROUND: vitamin D deficiency among older people results in poor bone and muscle health and an increased risk of fractures. In the UK, government initiatives and the launch of the Osteoporosis Strategy have been in place since 1998, highlighting the importance of adequate levels of vitamin D for its prevention. The aim of this analysis is to assess vitamin D status and examine associations of deficiency with risk factors among older people in England. METHODS: a valid vitamin D sample was obtained from 1,766 informants as part of the Health Survey for England (HSE) 2000, a nationally representative survey of people aged 65 and over living in institutions and private households in England. RESULTS: among both men and women in institutions, the prevalence of vitamin D deficiency was higher and mean serum vitamin D levels were significantly lower than among those in private households. Regression analyses showed that women were more likely to be vitamin D deficient than men (odds ratio (OR) 2.1) and deficiency was associated with limiting longstanding illness (OR 3.57), manual social classes (OR 2.4), poor general health (OR 1.92) and body mass index<25 kg/m2 (OR 2.02), and was 67% more likely among informants in the winter/autumn. Overall, the results show no significant improvements in vitamin D status in comparison to earlier National Diet and Nutrition Survey (NDNS) results. CONCLUSION: vitamin D deficiency exists at worrying levels among those aged 65 years and over. Further action is needed to alert health professionals about the risks related to vitamin D deficiency and extend the provision of prevention and treatment programmes targeted to those in need.     

维生素D和高血压发病的研究进展

维生素D缺乏非常普遍,流行病学和临床研究显示维生素D缺乏可能和高血压发病有关.维生素D可能通过负性调节肾素血管紧张素系统,减少甲状旁腺素分泌,改善胰岛素抵抗及对血管的保护作用降低高血压的发病风险,而且维生素D受体基因多态性也可能和高血压相关.开展维生素D和高血压发病的研究可能对高血压防治提供新的途径.     

Vitamin D and breast cancer risk

In addition to its important role in the maintenance of the skeleton, there is mounting evidence that vitamin D has effects on other body systems, and that adequate supplies of vitamin D are likely to be required for optimal health. Vitamin D is obtained both from dietary sources and from cutaneous synthesis with exposure to sunlight. Some epidemiological studies have indicated that vitamin D deficiency and decreased exposure to solar UVB radiation increase the risk of some cancers, including breast cancer. The active metabolite of vitamin D, 1,25-dihydroxy-vitamin D(3), is synthesized primarily in the kidney, and has been shown in laboratory studies to have potent anti-proliferative effects on breast cancer cells. Normal and neoplastic breast tissues contain the vitamin D receptor, and gene ablation studies have implicated the receptor in normal breast development. Several polymorphisms have been identified in the vitamin D receptor gene, and these have been associated with risk of breast cancer in some studies. Local synthesis of 1,25-dihydroxyvitamin D(3) in breast tissue may contribute to maintenance of normal cell function, which could be impaired in vitamin D deficiency.     

维生素D在慢性阻塞性肺疾病防治中作用的研究进展

维生素D缺乏和慢性阻塞性肺疾病(简称慢阻肺)均为世界公认的健康问题。慢阻肺是全球范围内第4大死因,其发病率和死亡率逐年上升。近年来,大量动物实验研究和临床观察研究均表明维生素D缺乏与慢阻肺相关。本文对维生素D在慢阻肺中的作用进行综述,旨在为慢阻肺的防治提供参考。     

The role of vitamin D in paediatric bone health

Recently there has been renewed interest in the role of vitamin D in paediatric bone health. Its role in the development of rickets and hypocalcaemia in infants and young children, in particular, in many part of the world is well known, and the importance of the prevention of vitamin D deficiency during pregnancy and lactation has been highlighted. Less clear are the possible effects that maintaining maternal vitamin D sufficiency might have on foetal and early infant growth and bone development. There is little evidence to suggest that maintaining childhood vitamin D status well above that necessary to prevent rickets has an effect on intestinal calcium absorption or on peak bone mass. Further studies are needed in these areas prior to definitive conclusions are drawn about the optimal vitamin D requirements and circulating 25(OH)D concentrations for foetal, infant and childhood bone health.     

Vitamin D and fracture prevention

Based on evidence from double-blind RCTs, vitamin D supplementation reduces falls and nonvertebral fractures, including those at the hip. However, this benefit is dose-dependent. According to 2 meta-analysis in 2009 of double-blind RCTs, no fall reduction was observed for a dose of less than 700 IU per day. A higher dose of 700 to 1000 IU supplemental vitamin D per day reduced falls by 19%. Similarly, no fracture reduction was observed for a received dose of 400 IU or less per day. A higher received dose of 482 to 770 IU supplemental vitamin D per day reduced nonvertebral fractures by 20% and hip fractures by 18%. The antifracture effect was present in all subgroups of the older population and was most pronounced among community-dwellers (-29%) and those ages 65 to 74 years (-33%). Consistently, fall prevention and nonvertebral fracture prevention increased significantly with higher achieved 25-hydroxyvitamin D levels in the 2009 meta-analyses. Fall prevention occurred with 25-hydroxyvitamin D levels of 60 to 95 nmol/L; levels of 75 to 112 nmol/L were required for nonvertebral fracture prevention. Given the absence of data beyond this beneficial range, these recent meta-analyses do not preclude the possibility that higher doses or higher achieved 25-hydroxyvitamin D concentrations would have been even more efficient in reducing falls and nonvertebral fractures.     

Who should receive calcium and vitamin D supplementation?

Combined calcium and vitamin D supplementation is recommended in the prevention and treatment of osteoporosis. Until recently, supplementation was perceived as harmless without adverse effects. However, recent meta-analyses have provided evidence suggesting that calcium supplements, whether or not in combination with vitamin D, may be associated with cardiovascular risks. Although this finding constitutes a safety signal that has to be taken seriously, these data have to be interpreted with some caution. Current data do not allow definite conclusions to be drawn, but require further independent confirmation, since in numerous large studies, combined calcium and vitamin D supplementation did not increase cardiovascular events, even in the most frail and elderly populations. Nevertheless, it seems appropriate to correct calcium deficiency preferably by enhancing dietary intake and to target supplementation on individuals at high risk of fracture or in whom calcium and vitamin D deficiency is highly prevalent. Other trials have shown an increased risk of falls and fractures with annual oral administration of high dose of vitamin D. Therefore, supplementation with more frequent, lower doses is preferred. Yet, the optimal dosing schedule is unknown and needs further study. In order to correct age-associated secondary hyperparathyroidism and to prevent osteoporotic fractures, a daily dose of 1,000-1,200?mg calcium and 800?IU vitamin D is recommended in elderly or institutionalised people, patients with established osteoporosis and individuals on glucocorticoids.     

Vitamin D Deficiency and Its Implications on Cardiovascular Disease

Vitamin D is widely known for its important role in bone health. More recent evidence suggests that vitamin D may also play a protective role in many chronic conditions, including cancer, autoimmune, kidney, and cardiovascular diseases (CVDs). Observational studies have associated low vitamin D levels with CVD risk factors, including hypertension, hyperlipidemia, diabetes, and metabolic syndrome, as well as with cardiovascular events, including stroke, myocardial infarction, and congestive heart failure. Much less evidence is available from clinical trials of vitamin D supplementation. It remains to be determined whether the vitamin D–CVD relationship is causal, and what dosing of vitamin D supplementation would be adequate for prevention. Large-scale randomized controlled trials with adequate vitamin D dosing are needed before treatment strategies can be implemented. The purpose of this article is to review the scientific evidence linking vitamin D deficiency with CVD, including explanations of potential biologic mechanisms.