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Background: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. Methods: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. Results: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225–326 AU) and 292 AU (95% CI, 246–338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, –86 to 53 AU; P =0.64). The mean change in aortic valve area was 0.02 cm 2 (95% CI, –0.09 to 0.12 cm 2 ; P =0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, –0.11 to 0.02 m/s; P =0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P =0.99), all-cause death (1 versus 4 patients; P =0.37), or cardiovascular events (10 versus 10 patients; P =0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (–212 pmol/L versus 45 pmol/L; P Conclusions: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03243890.

Purpose Peripheral neuropathy (PN) is common in multiple myeloma (MM) patients. More insight has been gained concerning the role of vitamin D in preventing PN. However, studies evaluating the effects of vitamin D3 supplementation on PN are lacking. The aims of this study are to (1) evaluate the effectiveness of a vitamin D3 regimen on achieving adequate vitamin D levels in deficient MM patients and to (2) exploratively evaluate the effect of vitamin D3 supplementation on PN. Methods Thirty-nine MM patients with inadequate (3 for 6 months according to a dose escalation regimen that consisted of one or two loading doses of 200,000 international units (IU), and maintenance doses of 800, 1600, or 3200 IU/day depending on the 25(OH)D level. A validated questionnaire was used to measure PN. Results Median 25(OH)D increased from 38 (IQR 32–52) nmol/L at baseline to 77 (IQR 72–87) nmol/L after 6 months (P P = 0.007). Conclusion The use of substantially higher vitamin D3 doses than recommended in current guidelines resulted in a significant increase in vitamin D levels in MM patients. Furthermore, evaluation of PN showed a significant decrease in PN grading. However, this exploratory evaluation needs further confirmatory research.

BACKGROUND: There is a growing body of human, animal and in vitro studies on vitamin D (vit D) substitution in endometriosis. The aim of this systematic review is to critically appraise and qualitatively synthesize the results of the available studies that examine the supplementation of vit D for endometriosis treatment.METHODS: A systematic search of the literature was conducted in four electronic databases (Medline, Cochrane, Scopus, Embase) and grey literature for original research articles on humans, animals and in vitro models published in any language.RESULTS: Four human studies, four animal studies and four in vitro studies were included. Quantitative synthesis of human studies showed no significant effect of vit D intake for dysmenorrhea (2 studies, 44 vit D vs 44 placebo, mean -0.71, 95% CI -1.94, 0.51) and non-cyclic pelvic pain (2 studies, 42 vit D vs 38 placebo, mean 0.34, 95% CI -0.02, 0.71). Regarding reproductive outcomes in women with endometriosis after in vitro fertilization, the only available study showed no differences between women taking vit D and women taking placebo. Three of the four included animal studies showed regression of endometriotic implants when treated with vit D. The in vitro studies demonstrated that vit D decreases invasion and proliferation of endometriotic lesions without affecting apoptosis.CONCLUSIONS: Although in vitro and animal studies suggest regression of the endometriotic implants and decrease of invasion and proliferation after vit D supplementation, this was not reflected in the results of the meta-analysis, which showed no benefit of vit D supplementation in patients with endometriosis and dysmenorrhea or non-cyclic pelvic pain as well as on the outcome of IVF treatment. However, given the heterogeneity and the diversity of the available studies, more research is required to shed light on the role of vit D supplementation in women with endometriosis.

ObjectiveTo determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) DesignPhase 3 open label randomised controlled trial.SettingUnited Kingdom.Participants6200 people aged ≥16 years who were not taking vitamin D supplements at baseline.InterventionsOffer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration Main outcome measuresThe primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat.ResultsOf 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations ConclusionsAmong people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19.Trial registrationClinicalTrials.govNCT04579640.

The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.

Vitamin D deficiency is so frequent in older patients (aged 65 years and older) that the international consensus does not recommend routine vitamin D measurement. Assessment of overall health status is a cornerstone before considering vitamin D supplementation, as the effect of vitamin D supplementation has only been demonstrated in vulnerable or dependent but not for robust older patients. The effect of the different modalities of oral vitamin D supplementation are equivalent : 800-1'200 IU/day, 10'000 IU/week or 30'000-50'000 IU/month. Monitoring of vitamin D blood level monitoring is not necessary because of a large therapeutic margin. In the presence of osteoporosis, a dietary or supplementation intake of 1'200 mg per day of calcium should be added.

Objective To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. Design Multinational network cohort study. Setting Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. Participants 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. Main outcome measures Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. Results Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from Conclusions Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

Contains fulltext : 242636.pdf (Publisher’s version ) (Open Access) BACKGROUND: Currently, no formalized international consensus guidelines exist to direct optimal topical treatment including long-term treatment. OBJECTIVE: In this survey, we aim to examine if and which topicals are used in clinical practice in long-term continuous treatment of psoriasis and how topicals are used in treating specific sites of the body. METHODS: A questionnaire was distributed electronically to dermatologists from the International Psoriasis Council (IPC) representing 26 countries. RESULTS: The top three topicals used across all severities of disease were topical corticosteroids, vitamin D analogs, and potent topical corticosteroids in combination with vitamin D analogs. On locations where the skin is thin, flexural and genital psoriasis, lower potency topical corticosteroids were used, whereas on other sites, in particular in palmoplantar psoriasis, superpotent topical corticosteroids and combination vitamin D analogs/corticosteroids were used. CONCLUSIONS: It is relevant to optimize localized therapy for all severities of psoriasis reconciling disease activity (stable vs. unstable disease), localization of the lesions and the individual patient and his/her perspectives on disease control. Topical therapies are valuable treatments for classical mild disease and may have a position in some patients with more severe manifestations.

The older-adult population is constantly increasing, hence aging and mechanisms leading to aging are a topic raising increasing interest. Hypovitaminosis D is common amongst old patients and has been proposed as causative of several chronic diseases. Here we review the role of hypovitaminosis D and vitamin D supplementation in sarcopenia and dementia, from bench to bedside.

Le déficit en vitamine D est en augmentation en Suisse. Si les cas de rachitisme restent peu fréquents, les pédiatres sont souvent confrontés à un déficit en vitamine D. Cette augmentation est en lien avec les changements des habitudes de vie sur les dernières décennies. Le déficit en vitamine D se présente sous plusieurs formes et le traitement varie en fonction du degré du déficit et des symptômes. Le rachitisme carentiel est la forme la plus fréquente de rachitisme et concerne principalement les populations avec des facteurs de risque. Le diagnostic différentiel comprend le rachitisme pseudo-carentiel et le rachitisme hypophosphatémique. Quand et chez qui le praticien doit-il suspecter un déficit en vitamine D ou un rachitisme ? Le diagnostic différentiel et les aspects pratiques du traitement sont présentés dans cet article.

International audience; The current surge of interest in vitamin D is fuelled not only by evidence that vitamin D supplementation decreases the risk of osteoporotic fractures but also by vast observational studies indicating a variety of beneficial extraskeletal effects (including decreases in the risks of cancer, inflammatory diseases, and even death). Serum 25-hydroxyvitamin D (25(OH)D) assay is now a highly reliable method for evaluating vitamin D stores in individual patients. Nevertheless, the normal or desirable 25(OH)D range for patients seen in everyday clinical practice needs to be more accurately defined. Maintaining serum 25(OH)D above 75nmol/L is currently recommended to ensure optimal bone health, but higher levels may be required to obtain some of the extraskeletal benefits. Naturally occurring vitamin D is by far the most widely used form for correcting vitamin D deficiency, and the hydroxylated derivatives have only a few highly specific indications. However, controversy persists about the optimal modalities of natural vitamin D supplementation in terms of the type of vitamin (D2 or D3), schedule (once daily or at wider intervals), and route (oral or injectable). For chronic supplementation to protect against bone loss, a daily dosage of at least 800IU seems required. Higher dosages (e.g., 100,000 to 200,000IU every 2months for 6months) may be needed to correct established vitamin D deficiency; a repeat 25(OH)D assay after 4 to 6months may help to assess the treatment response and to adjust the subsequent vitamin D dosage. The current emphasis is on the detection of vitamin D deficiency in the general population and in subgroups at risk for osteoporosis followed by an assessment of severity and the initiation of appropriate treatment. From a public health perspective, supplying at least 800IU per day seems useful and safe.

PURPOSE: To compare responsiveness Short Form-36 (SF-36), Nottingham Health Profile (NHP), and QUALEFFO-41 scales in patients diagnosed with osteoporosis. METHODS: A number of 70 osteoporosis patients who were in their menopause period at least for three years were enrolled in our study. The patients completed Short Form-36 (SF-36), Nottingham Health Profile (NHP), and QUALEFFO-41 scales during pretreatment period and one year after the termination of the treatment. Reponsiveness was compared between questionnaires using standardized responsiveness mean (SRM), the effect size (ES), and Guyatt's method., RESULTS: All scales revealed statistically significant improvement after the treatment. Upon this finding, calculations related with responsiveness indices for SF-36 (Physical Health and Mental Health), NHP (Total point), and QUALEFFO-41 (Total point) demonstrated highly responsive. ES=1.67 and 1.55, SRM=1.55 and 1.85, Guyatt value=2.20 and 1.91 for SF-36 Physical Health and Mental Health. ES=1.35, SRM=1.35, Guyatt value=1.72 for NHP. QUALEFFO-41's ES=2.56, SRM=4.32 and Guyatt value=2.31. CONCLUSION: Osteoporosis specific scale as QUALEFFO-41, gives more specific information about the quality of life of osteoporotic patients. If patients with osteoporosis will be compared with other diseases regarding quality of life, then SF-36, one scale was used to evaluate general quality life of such patients, should be preferred against NHP. © 2014 IOS Press and the authors. All rights reserved.

The Latin American MS Experts' Forum has developed practical recommendations on the initiation and optimization of disease-modifying therapies in patients with relapsing–remitting multiple sclerosis (RRMS). The recommendations reflect the unique epidemiology of MS and the clinical practice environment in Latin American countries. Treatment response may be evaluated according to changes in relapses; progression, as assessed by the Expanded Disability Status Scale and the Timed 25-foot Walk; and lesion number on magnetic resonance imaging. Follow-up assessments are recommended every six months, or annually for stable patients. Cognitive function should be evaluated in all RRMS patients at baseline and annually thereafter. These recommendations are intended to assist clinicians in Latin America in developing a rational approach to treatment selection and sequencing for their RRMS patients.

Type 2 diadetes is associated with an increased risk of fractures. Calcium supplements are still in the middle of a cardiovascular controversy. Swiss recommandations are available for vitamin D supplementation. Zoledronate exerts a long-term remaining effect on bone resorption. After 5 years treatment with denosumab, fracture incidence remains low. Atypical femoral fractures associated with bisphosphonates treatment have been evaluated in the university hospital of Geneva.

Studies exploring the effect of calcium supplementation on cardiovascular risk suggest that systolic blood pressure decreases with supplementation. A lower calcium intake has been associated with an increased risk of stroke. By contrast, calcium supplementation may increase the risk of myocardial infarction. The effect of vitamin D supplementation on blood pressure is still unclear and no effect of vitamin D supplementation on coronary heart disease or stroke has been clearly demonstrated. There is a lack of randomized clinical trials primarily addressing the effect of these parameters on CVD. Currently, the use of calcium and vitamin D supplementations for the prevention of cardiovascular disease is not justified.

Methods: Between 1999 and 2010, a total of 477 patients 50 years and older were hospitalized with a subtrochanteric or femoral shaft fracture at a single university medical center. Admission radiographs and medical and treatment records were examined, and patients were classified as having atypical or classic femoral fractures. A random sample of 200 healthy individuals without femoral fracture were also identified. Multivariate logistic regression was used to assess the association of bisphosphonate use and atypical femoral fracture, and the incidence rates of each type of fracture over time were calculated. Results: Thirty-nine patients with atypical fractures and 438 patients with classic fractures were identified. Of the patients with atypical fractures, 32 (82.1%) had been treated with bisphosphonates compared with 28 (6.4%) in the classic fractures group (odds ratios [OR], 66.9; 95% CI, 27.1-165.1) and 11.5% in the group without fracture (OR, 35.2; 95% CI, 13.9-88.8). Bisphosphonate use was associated with a 47% reduction in risk of classic fracture (OR, 0.5; 95% CI, 0.3-0.9). Considering the duration of use, the ORs (95% CIs) for atypical fractures were 35.1 (10.0-123.6) for less than 2 years, 46.9 (14.2154.4) for 2 to 5 years, 117.1 (34.2-401.7) for 5 to 9 years, and 175.7 (30.0-1027.6) for more than 9 years compared with no use. A contralateral fracture occurred in 28.2% of atypical cases and in 0.9% of classic cases (OR, 42.6; 95% CI, 12.8-142.4). The incidence rate of atypical fractures was low (32 cases per million personyears) and increased by 10.7% per year on average. Conclusions: Atypical femoral fractures were associated with bisphosphonate use; longer duration of treatment resulted in augmented risk. The incidence of atypical fractures increased over a 12-year period, but the absolute number of such fractures is very small.

Calcium supplements should be used according to the dietary intakes. Daily vitamin D supplements have beneficial on bone and extraskeletal effects. Denosumab is registered in Switzerland for the treatment of postmenopausal osteoporosis and to prevent bone loss induced by sex hormone deprivation therapies in men and women. Zoledronate has a long-term efficacy on bone resorption in postmenopausal women and prevents bone loss induced by sex hormone deprivation therapies in both sexes. Teriparatide exerts beneficial effects on maxillary bone. Odanacatib decreases bone resorption and increases bone mineral density. Cinacalcet could be used as long-term treatment in case of hyperparathyroidism. Adverse events associated with the use of bisphosphonate are still under discussion. Strontium ranelate will not be introduced in Switzerland.

A nationwide survey was conducted in Switzerland to assess the quality level of osteoporosis management in patients aged 50 years or older presenting with a fragility fracture to the emergency ward of the participating hospitals. Eight centres recruited 4966 consecutive patients who presented with one or more fractures between 2004 and 2006. Of these, 3667 (2797 women, 73.8 years old and 870 men, 73.0 years old in average) were considered as having a fragility fracture and included in the survey. Included patients presented with a fracture of the upper limbs (30.7%), lower limbs (26.4%), axial skeleton (19.5%) or another localisation, including malleolar fractures (23.4%). Thirty-two percent reported one or more previous fractures during adulthood. Of the 2941 (80.2%) hospitalised women and men, only half returned home after discharge. During diagnostic workup, dual x-ray absorptiometry (DXA) measurement was performed in 31.4% of the patients only. Of those 46.0% had a T-score < or =-2.5 SD and 81.1% < or =-1.0 SD. Osteoporosis treatment rate increased from 26.3% before fracture to 46.9% after fracture in women and from 13.0% to 30.3% in men. However, only 24.0% of the women and 13.8% of the men were finally adequately treated with a bone active substance, generally an oral bisphosphonate, with or without calcium / vitamin D supplements. A positive history of previous fracture vs none increased the likelihood of getting treatment with a bone active substance (36.6 vs 17.9%, ? 18.7%, 95% CI 15.1 to 22.3, and 22.6 vs 9.9%, ? 12.7%, CI 7.3 to 18.5, in women and men, respectively). In Switzerland, osteoporosis remains underdiagnosed and undertreated in patients aged 50 years and older presenting with a fragility fracture.

Lung-transplant recipients are at risk of osteoporosis. They may have low bone mass even before posttransplantation immunosuppressive therapy. We studied bone mineral density (BMD) before and after lung transplantation and compared the efficacy of antiresorptive therapies to calcium and vitamin D supplementation.Areal BMD was assessed in 42 patients awaiting lung transplantation and measured again after surgery at 6 (n = 29), and at 12 months (n = 20). Nineteen patients received antiresorptive therapy (30 mg pamidronate IV every 3 months (n = 14), or hormonal replacement therapy (n = 5)), and 10 patients received only calcium and vitamin D supplements.Mean age- and gender-adjusted lumbar spine (LS) and femoral neck (FN) BMD was significantly decreased prior to transplantation (- 0.6 +/- 0.2, p0.01, and - 1.5 +/- 0.2 standard deviation, p0.001, respectively). At that time, 29% were osteoporotic (T-score- 2.5 below the peak bone mass), while 55% were below - 1.0 T-score. Antiresorptive therapy decreased the rate of LS bone loss during the first 6 months and led to a significant increase of BMD at 1 year, with LS changes of + 0.2 +/- 0.1 vs - 0.4 +/- 0.1 Z-score in the calcium-vitamin D group (p0.002), and + 0.2 +/- 0.1 vs - 0.04 +/- 0.1 for FN (NS). One out of 20 patients experienced clinically evident fractures during antiresorptive therapy, and 3 out of 12 in the calcium-vitamin D group.A significant proportion of patients awaiting lung transplantation was osteoporotic or osteopenic. Antiresorptive therapy (pamidronate or hormone-replacement therapy (HRT)) prevented accelerated LS bone loss after graft.

Amino acid excretion was investigated in 21 rachitic infants and in 22 of their parents. There was (a) increased alpha-amino acid excretion in one-third of the infants a long time after the rickets had healed, (b) an abnormally high excretion of alpha-amino nitrogen and of phosphorus in many of the parents (c) an abnormal pattern of amino acid excretion in all 9 infants tested, and (d) a good correlation between the excretion of individual amino acids by an infant and by its parents. Our findings suggest that in at least some cases of nutritional rickets there is a genetic element which may manifest itself only under adverse environmental conditions. Archives of Disease in Childhood

Rickets continues to occur even in warm countries like Greece. This is the first population survey of the incidence of biochemical evidence of rickets in a random sample of infants living in both uraban and rural areas. The authors examine the medical and social factors responsible for the occurrence of this preventable disease, and they present additional evidence that rickets may be a disease in which a genetically transmitted defect becomes evident under adverse environmental conditions.