Revisiting the significance of nano-vitamin D for food fortification and therapeutic application.

OBJECTIVE: Vitamin D (a prohormone) is an important micronutrient required by the body for skeletal homeostasis and a range of non-skeletal actions. Calcitriol, the active form of vitamin D, regulates a variety of cellular and metabolic processes through both genomic and nongenomic pathways. Often prescribed for treating rickets and osteoporosis, vitamin D deficiency can exacerbate various other medical conditions. SIGNIFICANCE, METHODS, AND RESULTS: Despite its multifunctional uses, the sensitivity of vitamin D makes formulating an efficient drug delivery system a challenging task, which is further complicated by its poor aqueous solubility. Enhancing the oral absorption of vitamin D is vital in utilizing its full efficacy. Recent developments in encapsulation and nanotechnology have shown promising results in overcoming these constraints. CONCLUSION: This review thus offers an insight to adequately comprehend the mechanistic pharmacology of vitamin D, its pathophysiological role, and justification of its medical indications, along with the benefits of utilizing nanotechnology for vitamin D delivery.

Parenteral iron therapy and phosphorus homeostasis: A review.

Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.

Autophagy efficacy and vitamin D status: Population effects.

Toll-like receptor (TLR) 2/1 signalling is linked to autophagy through transcriptional actions of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-vitamin D receptor (VDR) complex. Population-specific effects have been reported for TLR2/1-VDR signalling. We hypothesized that population effects extend to autophagy and are influenced by vitamin D status. Serum 25(OH)D3 of healthy South Africans (Black individuals n = 10, White individuals n = 10) was quantified by LC-MS/MS. Primary monocytes-macrophages were supplemented in vitro with 1,25(OH)2D3 and stimulated with the lipoprotein Pam3CysSerLys4. TLR2, VDR, hCAP18, Beclin1, LC3-IIB, cytokines and CYP24A1 mRNA were quantified by flow cytometry and RT-qPCR, respectively. Black individuals showed significantly lower overall cumulative LC3-IIB (P < 0.010), but higher Beclin1, VDR, IL6 and TNFA (P < 0.050) than White individuals. 1,25(OH)2D3 enhanced autophagic flux in monocytes-macrophages from Black individuals upon TLR2/1 stimulation and strengthened autophagy in 25(OH)D3 deficient individuals (independent cohort, n = 20). These findings support population-directed vitamin D supplementation.

Native vitamin D in pre-dialysis chronic kidney disease.

Chronic kidney disease patients have a high prevalence of vitamin D insufficiency/deficiency. Vitamin D deficiency has been associated with a variety of bone, metabolic and cardiovascular disorders. However, the role of native vitamin D supplementation (ergocalciferol, cholecalciferol or calcifediol) remains unclear in chronic kidney disease (CKD), particularly in the pre-dialytic phase. Several international guidelines have been developed on CKD-Mineral and Bone Disorder, but the optimal strategy for native vitamin D supplementation and its clinical benefit remains a subject of debate in the scientific community. This paper aims to review the available literature, including randomized clinical trials that evaluated the effects of native vitamin D supplementation on pre-dialysis CKD on biochemical and clinically relevant outcomes.

Vitamin D Supplementation Modestly Reduces Serum Iron Indices of Healthy Arab Adolescents.

Vitamin D deficiency has been shown to affect iron status via decreased calcitriol production, translating to decreased erythropoiesis. The present study aimed to determine for the first time whether vitamin D supplementation can affect iron levels among Arab adolescents. A total of 125 out of the initial 200 Saudi adolescents with vitamin D deficiency (serum 25(OH)D < 50 nmol/L) were selected from the Vitamin D-School Project of King Saud University in Riyadh, Saudi Arabia. Cluster randomization was done in schools, and students received either vitamin D tablets (1000 IU/day) (N = 53, mean age 14.1 ± 1.0 years) or vitamin D-fortified milk (40IU/200mL) (N = 72, mean age 14.8 ± 1.4 years). Both groups received nutritional counseling. Anthropometrics, glucose, lipids, iron indices, and 25(OH)D were measured at baseline and after six months. Within group analysis showed that post-intervention, serum 25(OH)D significantly increased by as much as 50%, and a parallel decrease of -42% (p-values <0.001 and 0.002, respectively) was observed in serum iron in the tablet group. These changes were not observed in the control group. Between-group analysis showed a clinically significant increase in serum 25(OH)D (p = 0.001) and decrease in iron (p < 0.001) in the tablet group. The present findings suggest a possible inhibitory role of vitamin D supplementation in the iron indices of healthy adolescents whose 25(OH)D levels are sub-optimal but not severely deficient, implying that the causal relationship between both micronutrients may be dependent on the severity of deficiency, type of iron disorder, and other vascular conditions that are known to affect hematologic indices. Well-designed, randomized trials are needed to confirm the present findings.

The role of vitamin D in reducing cancer risk and progression.

Vitamin D is not really a vitamin but the precursor to the potent steroid hormone calcitriol, which has widespread actions throughout the body. Calcitriol regulates numerous cellular pathways that could have a role in determining cancer risk and prognosis. Although epidemiological and early clinical trials are inconsistent, and randomized control trials in humans do not yet exist to conclusively support a beneficial role for vitamin D, accumulating results from preclinical and some clinical studies strongly suggest that vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome.

[Vitamin D and breast cancer: physiopathology, biological and clinical implications]. / Vitamine D et cancer du sein: physiopathologie, implications biologiques et cliniques.

There is a recent increase in interest of vitamin D and breast cancer, facing the number of publications on the subject. This increase have several reasons, on the one hand, vitamin D deficiency is more and more prevalent and, on the other hand, there are new data that highlights the extra-bone effects of vitamin D, especially in breast cancer, the vitamin D is involved in the breast cancer risk factor, the prognosis, and the interaction with breast cancer treatments. This combination between vitamin D deficiency and breast cancer is extremely usual, and combined with all cancer clinical parameters: the incidence, the tumour biology, the clinical presentation, the prognosis, and the antineoplastic treatment tolerance. This vitamin D deficiency is increased after adjuvant cancer treatments. And yet, this problem increases bone metabolism disruptions in breast cancer patients, inducing osteoporotic risk at long time, even though this population is curable. This problem is therefore serious in the adjuvant breast cancer treatment. Unfortunately, in this population, the current recommendations are clearly insufficient, and the current randomized clinical trial results would contribute to define the best way to correct the vitamin D deficiency, quickly and secure.

Vitamin D in liver diseases: from mechanisms to clinical trials.

Traditionally regarded as a typical vitamin regulating calcium and phosphorus homeostasis, vitamin D is now discovered as a highly versatile molecule with emerging roles in immunity, cancer, infectious diseases, fibrosis, fatty liver diseases, and alcoholic liver diseases. A large body of clinical evidence has demonstrated the prevalence and risks of vitamin D deficiency in various chronic diseases. Biologically active vitamin D, 1,25-dihydroxylvitamin D3, is synthesized in two distinct systems. In addition to the classic two-step hydroxylation in the liver and kidneys, 1,25-dihydroxylvitamin D3 can also be produced locally by immune cells in response to infection. The bioactive vitamin D generated in these two pools apparently functions differently: while the former facilitates calcium adsorption and homeostasis, the latter confers immune regulation. The immune regulatory functions of vitamin D are demonstrated by induction of antimicrobial peptides, suppression of innate immune response, induction of Th2 cytokines, and stimulation of T-regulatory T cells. Vitamin D deficiency or insufficiency is overwhelmingly associated with viral hepatitis, cirrhosis, and fatty liver diseases. Recent clinical trials have shown that vitamin D supplements significantly enhance the efficacy of interferon plus ribavirin therapy through sustained virological response. A recent study showed that 25-dihydroxyvitamin D rather than 1,25-dihydroxyvitamin D could directly suppress hepatitis C virus assembly. Moreover, clinical evidence has shown that vitamin D deficiency is associated with alcoholic and non-alcoholic fatty liver diseases. In this review, we highlight some recent advances in vitamin D researches and clinical trails.

MicroRNA-627 mediates the epigenetic mechanisms of vitamin D to suppress proliferation of human colorectal cancer cells and growth of xenograft tumors in mice.

BACKGROUND & AIMS: Vitamin D protects against colorectal cancer through unclear mechanisms. We investigated the effects of calcitriol (1α,25-dihydroxyvitamin D3; the active form of vitamin D) on levels of different microRNAs (miRNAs) in colorectal cancer cells from humans and xenograft tumors in mice. METHODS: Expression of miRNAs in colorectal cancer cell lines was examined using the Ambion mirVana miRNA Bioarray. The effects of calcitriol on expression of miR-627 and cell proliferation were determined by real-time polymerase chain reaction and WST-1 assay, respectively; growth of colorectal xenograft tumors was examined in nude mice. Real-time polymerase chain reaction was used to analyze levels of miR-627 in human colon adenocarcinoma samples and nontumor colon mucosa tissues (controls). RESULTS: In HT-29 cells, miR-627 was the only miRNA significantly up-regulated by calcitriol. Jumonji domain containing 1A (JMJD1A), which encodes a histone demethylase, was found to be a target of miR-627. By down-regulating JMJD1A, miR-627 increased methylation of histone H3K9 and suppressed expression of proliferative factors, such as growth and differentiation factor 15. Calcitriol induced expression of miR-627, which down-regulated JMJD1A and suppressed growth of xenograft tumors from HCT-116 cells in nude mice. Overexpression of miR-627 prevented proliferation of colorectal cancer cell lines in culture and growth of xenograft tumors in mice. Conversely, blocking the activity of miR-627 inhibited the tumor suppressive effects of calcitriol in cultured colorectal cancer cells and in mice. Levels of miR-627 were decreased in human colon adenocarcinoma samples compared with controls. CONCLUSIONS: miR-627 mediates tumor-suppressive epigenetic activities of vitamin D on colorectal cancer cells and xenograft tumors in mice. The messenger RNA that encodes the histone demethylase JMJD1A is a direct target of miR-627. Reagents designed to target JMJD1A or its messenger RNA, or increase the function of miR-627, might have the same antitumor activities of vitamin D without the hypercalcemic side effects.

A comparison of vitamin D activity in paired non-malignant and malignant human breast tissues.

Links between a low vitamin D status and an increased risk of breast cancer have been observed in epidemiological studies. These links have been investigated in human tissue homogenates and cultured cell lines. We have used non-malignant, malignant and normal reduction mammoplasty breast tissues to investigate the biological and metabolic consequences of the application of vitamin D to intact ex vivo human breast tissue. Tissues were exposed to 1α,25(OH)(2)D(3) (1,25D; active metabolite) and 25(OH)D (25D; pre-metabolite). Changes in mRNA expression and protein expression after vitamin D exposure were analysed. Results indicate that while responses in normal and non-malignant breast tissues are similar between individuals, different tumour tissues are highly variable with regards to their gene expression and biological response. Collectively, malignant breast tissue responds well to active 1,25D, but not to the inactive pre-metabolite 25D. This may have consequences for the recommendation of vitamin D supplementation in breast cancer patients.

Chronic kidney disease--mineral and bone disorder: a complex scenario.

The chronic kidney disease-bone and mineral disorders (CKD-MBD) represents a dinamic area of research. Recently, new factors such as FGF-23 have been added to the classic list of regulators of bone metabolism, which include calcium, phosphorus, PTH and calcitriol. Vascular calcification, one of the most important complication of CKD-MBD is regulated by a complex variety of  promoters and inhibitors. The relationship between vascular calcification, bone loss and mortality, together with the existence of likely common signaling pathways are subject of interesting investigations.

TNFα inhibits the development of osteoclasts through osteoblast-derived GM-CSF.

Inflammatory cytokines such as tumor necrosis factor-alpha (TNFα) are potent stimulators of osteoclast formation and bone resorption and are frequently associated with pathologic bone metabolism. The cytokine exerts specific effects on its target cells and constitutes a part of the cellular microenvironment. Previously, TNFα was demonstrated to inhibit the development of osteoclasts in vitro via an osteoblast-mediated pathway. In the present study, the molecular mechanisms of the inhibition of osteoclastogenesis were investigated in co-cultures of osteoblasts and bone marrow cells (BMC) and in cultures of macrophage-colony stimulating factor (M-CSF) dependent, non-adherent osteoclast progenitor cells (OPC) grown with M-CSF and receptor activator of NF-κB ligand (RANKL). Granulocyte-macrophage colony stimulating factor (GM-CSF), a known inhibitor of osteoclastogenesis was found to be induced in osteoblasts treated with TNFα and the secreted protein accumulated in the supernatant. Dexamethasone (Dex), an anti-inflammatory steroid, caused a decrease in GM-CSF expression, leading to partial recovery of osteoclast formation. Flow cytometry analysis revealed that in cultures of OPC, supplemented with 10% conditioned medium (CM) from osteoblasts treated with TNFα/1,25(OH)(2)D(3), expression of RANK and CD11c was suppressed. The decrease in RANK expression may be explained by the finding, that GM-CSF and the CM from wt osteoblasts were found to suppress the expression of c-Fos, Fra-1, and Nfatc-1. The failure of OPC to develop into CD11c(+) dendritic cells suggests that cell development is not deviated to an alternative differentiation pathway, but rather, that the monocytes are maintained in an undifferentiated, F4/80(+), state. The data further implies possible interactions among inflammatory cytokines. GM-CSF induced by TNFα acts on early hematopoietic precursors, inhibiting osteoclastogenesis while acting as the growth factor for M-CSF independent inflammatory macrophages. These in turn may condition a microenvironment enhancing osteoclast differentiation and bone resorption upon migration of the OPC from circulation to the bone/bone marrow compartment.

[The role of calcium, calcitriol and their receptors in parathyroid regulation]. / Papel de calcio, calcitriol y sus receptores en la regulación de la paratiroides.

The mechanism of regulation of Parathyroid hormone (PTH) is complex, and diverse factors are involved: the fundamental ones are calcium, calcitriol and phosphorus. Calcium and calcitriol's mechanism of action takes place through its specific receptors, the calcium-sensing receptor (CaR) and the Vitamin D Receptor (VDR). These two factors have an effect not only on its specific receptors, but also they can modify the other receptor in a positive manner, promoting its actions and demonstrating a cooperative effect between the two. Along with calcium and calcitriol, drugs used in the treatment of Chronic Kidney Disease Mineral Bone Disorders (CKD-MBD) also act directly or indirectly on CaR and VDR and therefore are also responsible for the regulation of the parathyroid gland.

Immunomodulatory effects of Vitamin D in multiple sclerosis.

Although Vitamin D is best known as a modulator of calcium homeostasis, it also has immune modulating potential. A protective effect of Vitamin D on multiple sclerosis is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements. Moreover, high circulating levels of Vitamin D have been associated with lower risk of multiple sclerosis. In this study, we measured 1,25 (OH)(2) Vitamin D and 25 (OH) Vitamin D levels in multiple sclerosis patients separated into different clinical subgroups according to disease status. In addition, direct effects of 1,25 (OH)(2) Vitamin D on ex vivo CD4+ T cells and myelin-peptide specific T cell lines were investigated to gain more insight into putative regulatory mechanisms in the disease pathogenesis. One hundred and thirty-two Hispanic patients with clinically definite multiple sclerosis were studied, 58 with relapsing remitting multiple sclerosis during remission, 34 during relapse and 40 primary progressive multiple sclerosis cases. Sixty healthy individuals matched with respect to place of residence, race/ethnicity, age and gender served as controls. Levels of 25(OH)D(3) and 1,25(OH)(2)D(3), measured by ELISA were significantly lower in relapsing-remitting patients than in controls. In addition, levels in patients suffering relapse were lower than during remissions. In contrast, primary progressive patients showed similar values to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific T cells was significantly inhibited by 1,25(OH)(2)D(3). Moreover, activated Vitamin D enhanced the development of IL-10 producing cells, and reduced the number of IL-6 and IL-17 secreting cells. Notably, Vitamin D receptor expression was induced by 1,25(OH)(2)D(3) in both activated and resting cells. Interestingly, T cells were able to metabolize 25(OH)D(3) into biologically active 1,25(OH)(2)D(3), since T cells express alpha1-hydroxylase constitutively. Finally, 1,25(OH)(2)D(3) also increased the expression and biological activity of indoleamine 2,3-dioxygenase, mediating significant increase in the number of CD4+CD25+ T regulatory cells. Collectively, these data suggest that 1,25(OH)(2)D(3) plays an important role in T cell homeostasis during the course of multiple sclerosis, thus making correction of its deficiency may be useful during treatment of the disease.

Pathogenesis of bone and mineral related disorders in chronic kidney disease: key role of hyperphosphatemia.

This paper reviews the pathogenesis of hyperphosphataemia and its role in the regulation of parathyroid hormone synthesis and parathyroid cell proliferation in chronic kidney disease. The association between hyperphosphaemia and vascular calcification, and the interventions that can be used to control plasma phosphate are also discussed.

Expanding role for vitamin D in chronic kidney disease: importance of blood 25-OH-D levels and extra-renal 1alpha-hydroxylase in the classical and nonclassical actions of 1alpha,25-dihydroxyvitamin D(3).

Recent advances in the understanding of vitamin D have revolutionized our view of this old nutritional factor and suggested that it has much wider effects on the body than ever believed before. In addition to its well-known effects on calcium/phosphate homeostasis, vitamin D, through its hormonal form, 1alpha,25-dihydroxyvitamin D(3) or calcitriol, is a cell differentiating factor and anti-proliferative agent with actions on a variety of tissues around the body (e.g., skin, muscle, immune system). By influencing gene expression in multiple tissues, calcitriol influences many physiological processes besides calcium/phosphate homeostasis including muscle and keratinocyte differentiation, insulin secretion, blood pressure regulation, and the immune response. The incidence of various diseases including epithelial cancers, multiple sclerosis, muscle weakness as well as bone-related disorders has been correlated with vitamin D deficiency/insufficiency and has led to a re-evaluation of recommended daily intakes both in the normal subject and CKD patient. Critical developments have been the emergence of the value of blood 25-OH-D measurement as a tool in predicting vitamin D-related problems and this has in turn emphasized the importance of the extra-renal version of the 1alpha-hydroxylase, the enzyme responsible for the final step in vitamin D activation. The widespread expression of this extra-renal enzyme supports the view that it exists to boost intracellular concentrations of calcitriol within some target tissues in order to modulate a unique set of genes specifically in those tissues, a process which is therefore dependent upon circulating 25-OH-D. For CKD patients with their tendency to vitamin D substrate insufficiency coupled with their documented loss of the renal 1alpha-hydroxylase in late stages, this new information has profound implications. Physicians must start to manage the vitamin D insufficiency by vitamin D supplements throughout stages 1-5 whilst continuing to provide calcitriol replacement therapy, in the form of calcitriol or its analogs, in stages 3-5.

Annual change in bone mineral density in predialysis patients with chronic renal failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D.

Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The aim of this study was to examine how a decrease in renal function affects annual bone mineral density (BMD) changes in predialysis CRF patients and to examine the factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF patients (age, 61.3 +/- 10.8 years; serum creatinine 2.7 +/- 1.2 mg/dl) was measured by peripheral quantitative computed tomography (pQCT) twice with a 1-year interval. The total BMD of the radius significantly decreased over a year (P < 0.001), and both trabecular and cortical BMD showed a significant decrease. Significant positive correlations with BMD changes were found for estimated creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)(2)D (r = 0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger reductions in creatinine clearance and serum 1,25(OH)(2)D. Of several bone metabolic markers examined, baseline serum osteocalcin was significantly positively correlated with annual BMD changes (r = -0.276, P < 0.05). Multiple regression analysis showed that baseline serum 1,25(OH)(2)D (beta = 0.434) was a significant predictor of decreases in total and trabecular BMD (R (2) = 0.188, P < 0.01; and R (2) = 0.207, P < 0.01), independent of other confounding factors. These results indicate that BMD decreases as renal function deteriorates in predialysis CRF patients, and that osteocalcin is a clinically useful marker associated with the decrease in BMD. The serum 1,25(OH)(2)D level is the principal factor affecting BMD of the radius, suggesting that supplementation with an active form of vitamin D is of importance for predialysis CRF patients.

A potential role for vitamin D on HIV infection?

Despite advances in the knowledge of vitamin D's potent immunomodulatory activity, its role on HIV disease progression is unknown. Decreased concentrations of 1alpha,25-hydroxyvitamin D3, or 1,25(OH)2D, the active form of vitamin D, have been reported among HIV-infected people and attributed to defects in renal hydroxylation and increased utilization. A few studies also described low levels of 25-hydroxyvitamin D3, 25(OH)D, the vitamin obtained from solar synthesis and diet. An inverse association between 1,25(OH)2D concentrations and mortality has been reported from a small cohort of HIV-infected adults, and some cross-sectional studies have indicated positive correlations between 1,25(OH)2D and CD4+ cell counts. Additional observational studies are needed to confirm the associations between vitamin D status and HIV disease progression. These investigations would provide useful insights on the potential role of vitamin D supplementation to HIV-infected persons and the planning of intervention trials.

Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats.

Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated with hyperphosphatemia in patients with chronic renal insufficiency (CRI). We proposed that changes in serum PTH and FGF23 levels might be associated with changes in serum phosphorus levels caused by the phosphate binder sevelamer hydrochloride (sevelamer, i.e. crosslinked poly[allylamine hydrochloride]). Rats were fed a diet containing adenine for 4 weeks to establish CRI. Animals were then offered either a normal diet or a diet containing 1 or 3% sevelamer for 8 weeks continuously, or intermittently with sevelamer diet or a normal diet offered for alternating 2-week periods. Changes in the serum levels of phosphorus, calcium, PTH, FGF23, and 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) were monitored over time. Adenine-treated rats developed severe CRI, with markedly elevated serum levels of phosphorus, PTH and FGF23, and reduced levels of serum 1,25(OH)(2)D(3). Continuous treatment with sevelamer suppressed these increases throughout the study period. Serum phosphorus, PTH, and FGF23 levels decreased rapidly when sevelamer treatments commenced and recovered rapidly once they were discontinued. However, the changes in serum FGF23 levels began after the onset of changes in serum phosphorus and PTH levels. In conclusion, circulating PTH, and FGF23 levels can be promptly manipulated through the control of serum phosphorus levels. Moreover, phosphate-binder treatment can effectively inhibit the elevation of serum FGF23 levels, as well as PTH levels, under conditions of CRI.

[Role of vitamin D in the neuro-muscular function]. / Papel da vitamina D na função neuro-muscular.

Through its action in the kidney, intestines, bone and parathyroid glands vitamin D is a major regulator of calcium homeostasis and for the development of a healthy skeleton. Moreover, receptors for this hormone are present in almost all body tissues and other actions which are not related to the mineral metabolism have been imputed to it. In the skeletal muscle cell, vitamin D acts through the classic mechanism of binding to a nuclear receptor and also by binding to a membrane receptor, carrying out actions that involve calcium transport, protein synthesis and kinetics of muscle contraction. Clinically, vitamin D deficiency, which is very common among the elderly, including the ones in our country, has been related to an increase in the incidence of falls, as well as the reduction of muscle strength and deterioration of body sway, evaluated by the oscillation of the body in the erect position. On the other hand, it has been demonstrated that supplementation of calcium associated to vitamin D in deficient elderly contributes to the improvement of these aspects of the neuro-muscular function. In this review, the mechanisms involved in the association between vitamin D and neuro-muscular function will be discussed, as well as the supplementation of vitamin D and calcium to prevent non-vertebral osteoporotic fractures under the perspective of the neuro-muscular effects.