Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group.

Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration.

Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D.

Clinical utility of bone turnover markers in patients with chronic kidney disease.

PURPOSE OF REVIEW: The burden of fractures is very high in patients with chronic kidney disease (CKD). It is increasingly recognized that knowledge of bone turnover is of paramount importance in guiding mineral metabolism and osteoporosis therapy in CKD. Bone histomorphometry is the gold standard to assess bone turnover, but is seldomly performed in clinical practice. Bone turnover markers (BTMs) may be the long awaited noninvasive diagnostic that may help to close the therapeutic gap in patients with advanced CKD presenting with bone fragility. RECENT FINDINGS: Mounting evidence indicates that BTMs may be useful in skeletal and nonskeletal risk stratification, in guiding mineral metabolism and osteoporosis therapy, and in monitoring the therapeutic response. SUMMARY: BTMs provide information that is complementary to other clinical tests. It may be envisioned that in the near future, the assessment of nonkidney cleared BTMs may become part of routine clinical evaluation and monitoring of bone health in CKD patients, integrated with clinical risk factors, imaging data and, eventually, bone histomorphometry. Panels of BTMs will likely be more informative than single markers, and the same might hold true for trends as opposed to single time point data.

Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

Recommendations on the measurement and the clinical use of vitamin D metabolites and vitamin D binding protein - A position paper from the IFCC Committee on bone metabolism.

Vitamin D, an important hormone with a central role in calcium and phosphate homeostasis, is required for bone and muscle development as well as preservation of musculoskeletal function. The most abundant vitamin D metabolite is 25-hydroxyvitamin D [25(OH)D], which is currently considered the best marker to evaluate overall vitamin D status. 25(OH)D is therefore the most commonly measured metabolite in clinical practice. However, several other metabolites, although not broadly measured, are useful in certain clinical situations. Vitamin D and all its metabolites are circulating in blood bound to vitamin D binding protein, (VDBP). This highly polymorphic protein is not only the major transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites, but also participates in the transport of the 25(OH)D into the cell via a megalin/cubilin complex. The accurate measurement of 25(OH)D has proved a difficult task. Although a reference method and standardization program are available for 25(OH)D, the other vitamin D metabolites still lack this. Interpretation of results, creation of clinical supplementation, and generation of therapeutic guidelines require not only accurate measurements of vitamin D metabolites, but also the accurate measurements of several other "molecules" related with bone metabolism. IFCC understood this priority and a committee has been established with the task to support and continue the standardization processes of vitamin D metabolites along with other bone-related biomarkers. In this review, we present the position of this IFCC Committee on Bone Metabolism on the latest developments concerning the measurement and standardization of vitamin D metabolites and its binding protein, as well as clinical indications for their measurement and interpretation of the results.

Analytical Performance Specifications for 25-Hydroxyvitamin D Examinations.

Currently the 25-hydroxy vitamin D (25(OH)D) concentration is thought to be the best estimate of the vitamin D status of an individual. Unfortunately, its measurement remains complex, despite recent technological advances. We evaluated the biological variation (BV) of 25(OH)D in order to set analytical performance specifications (APS) for measurement uncertainty (MU). Six European laboratories recruited 91 healthy participants. The 25(OH)D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate on a Lumipulse G1200 (Fujirebio, Tokyo, Japan). The linear regression of the mean 25(OH)D concentrations at each blood collection showed that participants were not in a steady state. The dissection of the 10-sample collection into two subsets, namely collections 1-5 and 6-10, did not allow for correction of the lack of homogeneity: estimates of the within-subject BV ranged from 5.8% to 7.1% and the between-subject BV ranged from 25.0% to 39.2%. Methods that would differentiate a difference induced by 25(OH)D supplementation at p < 0.05 should have MU < 13.6%, while at p < 0.01, the MU should be <9.6%. The development of APS using BV assumes a steady state of patients. The findings in this study suggest that patients are not in steady state. Therefore, APS that are based on MU appear to be more appropriate.

The Effects of 6-Month Vitamin D Supplementation during the Non-Surgical Treatment of Periodontitis in Vitamin-D-Deficient Patients: A Randomized Double-Blind Placebo-Controlled Study.

BACKGROUND: This study assessed the effects of weekly vitamin D (VD) supplementation on clinical and biological parameters after scaling and root planning (SRP) in the treatment of periodontitis and served to validate the VD dosage regimen. METHODS: It was a monocentric, randomized, double-blind, placebo-controlled clinical trial with 6 months follow-up. Healthy Caucasian periodontitis patients presenting serum 25(OH) vitamin D3 below 30 ng/mL were randomly allocated to test group (SRP + VD 25,000 international units (IU)/week) or the control group (SRP + placebo). RESULTS: A total of 59 patients were screened, 27 were included and 26 completed 3 months (M) and 21 completed 6M control. Test (n = 13) and control groups (n = 14) had similar 25(OH) vitamin D3 levels at baseline (17.6 ± 7.4 vs. 14.4 ± 5.2, respectively). After one month, there was a significant difference between groups (32.9 ± 5.2 vs. 16.1 ± 4.7), also seen at M3 and M6 (t-test, p < 0.001). Periodontal treatment was successful in both groups, since it resulted in a reduction of all measured clinical parameters at M3 and M6 (probing pocket depth (PPD), full mouth bleeding and plaque). However, the reduction in PPD was greater in the test group. CONCLUSIONS: In this short-term pilot study, no significant differences were observed between two groups. However, supplementation with VD tended to improve the treatment of periodontitis in patients with initial 25(OH) vitamin D3 < 30 ng/mL and proved safe and efficacious. NCT03162406.

Vitamin D for the older patient: from hype to hope?

PURPOSE OF REVIEW: The review critically appraises the most recent and important meta-analyses that have assessed the effect of vitamin D supplementation on bone health in the older population. RECENT FINDINGS: Vitamin D status is generally lower in study participants with bone wasting. However, studies on the effects of vitamin D supplementation on bone health, summarized in different meta-analyses, have provided conflicting results, likely because of the heterogeneity between studies. Interventional studies performed using more physiological doses of vitamin D (i.e. avoiding very large, nonphysiological doses) or in study participants with low vitamin D status have provided more beneficial effects on bone health. SUMMARY: Meta-analyses assessing the impact of vitamin D in the treatment of osteoporosis are heterogeneous in their conception or their results and sometimes have included inappropriate studies to answer the useful research question for the clinician, making the interpretation and the clinical use of these conflicting meta-analyses quite difficult.

Vitamin D Supplementation in France in patients with or at risk for osteoporosis: Recent data and new practices.

With intermittent vitamin D supplementation, serum 25-hydroxyvitamin D (25OHD) levels may remain stable only if the dosing interval is shorter than 3 months, the ideal perhaps being about 1 month. Recent data support moderate daily vitamin D doses instead of high intermittent doses, notably in elderly patients prone to falls. The level of evidence is low, however, with no head-to-head comparisons of clinical outcomes such as fractures and falls in groups given identical dosages daily versus intermittently. A challenge to daily vitamin D supplementation in France is the absence of a suitable pharmaceutical formulation. In addition, daily dosing carries a high risk of poor adherence. Until suitable vitamin D3 formulations such as tablets or soft capsules each containing 1000 or 1500 IU become available, we suggest intermittent supplementation according to 2011 GRIO guidelines. Among the available dosages, the lowest should be preferred, with the shortest possible interval, e.g., 50,000 IU monthly rather than 100,000 every two months.

Vitamin D, bone alkaline phosphatase and parathyroid hormone in healthy subjects and haemodialysed patients from West Africa: impact of reference ranges and parathyroid hormone generation assays on the KDIGO guidelines.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend targets based on multiples of the upper limit of normal (ULN) of parathyroid hormone (PTH) concentration. However, the ULN has not always been correctly established by manufacturers. While it is known that the ULN is supposed to be higher in African Americans than in Caucasians, it is largely unknown in Africans. METHODS: We established the ULN of PTH concentration in a population of 240 healthy Ivorians using second- and third-generation PTH assays before and after supplementation with 100 000 IU of cholecalferol. We measured the levels of PTH, bone alkaline phosphatase, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in 100 haemodialysed Ivorian patients. RESULTS: The prevalence of vitamin D deficiency in Ivory Coast is low. The ULN obtained using the third-generation PTH assay was similar to that obtained in Caucasians but was higher when PTH was measured using the second-generation PTH assay. According to the KDIGO guidelines, ∼20% of the haemodialysed patients were below twice the ULN and 30% were above nine times the ULN. Approximately 25% of the patients were even >12 times the ULN. We observed a discrepancy in the results between the two PTH assays (14%) that was relatively more important than what we observed from previous studies in Caucasians using the same strategy. CONCLUSIONS: We found a low prevalence of vitamin D deficiency in a tropical country like Ivory Coast. We also established the PTH reference range, which could prove useful for the follow-up of haemodialysed patients, particularly for the large number of patients suffering from secondary hyperparathyroidism who are at high risk of adverse bone events.

Vitamin D-Resistant Rickets and Cinacalcet-One More Favorable Experience.

Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder characterized by early onset of severe rickets, with a complete triad of clinical, biochemical and skeletal abnormalities. Homozygous or heterozygous mutations in the vitamin D receptor (VDR) gene leading to complete or partial target organ resistance to the action of 1α, 25-dihydroxyvitamin D3 (the active form of vitamin D) are responsible for HVDRR. Theoretically the therapeutic goal is to overcome this tissue resistance, and to normalize calcium and phosphate homeostasis. Practically, the treatment could be oriented to correct the secondary hyperparathyroidism to avoid long-term negative impact on bone health. The conventional therapeutic strategy (high-dose calcium plus active vitamin D metabolites) gives variable responses in magnitude and duration. We report a case of HVDRR with heterozygous mutation in the VDR gene, neonatal alopecia, and a severe clinical phenotype diagnosed at the age of 30 months who showed unsatisfactory response to traditional therapy. The short-term responsiveness to cinacalcet was encouraging, with adequate correction of phosphate-calcium homeostasis and significant improvement of clinical and radiological status at 6 months of treatment.

Light exposure via a head-mounted device suppresses melatonin and improves vigilant attention without affecting cortisol and comfort.

We aimed at assessing whether a head-mounted light therapy device, enriched in blue wavelengths, suppresses melatonin secretion and improves vigilant attention in the late evening hours. We also assessed whether using such light device is associated with discomfort and physiological stress. Seventeen healthy young participants (eight females) participated in a counterbalanced within-subject design during which they were exposed for 2 hr before habitual sleep time to a blue-enriched light (1500 lx) or to a lower intensity red-light (150 lx) control condition, using a new-generation light emitting diode (LED) head-mounted device. Compared to the red light control condition, blue-enriched light significantly reduced melatonin secretion and reaction times during a psychomotor vigilance task while no significant differences were detected in discomfort and cortisol levels. These results suggest that, compared to a control condition, blue-enriched light, delivered by a new-generation head-mounted device, elicits typical non-visual responses to light without detectable discomfort and physiological stress. They suggest that such devices might constitute an effective alternative to standard light boxes.

A Randomized Study to Compare a Monthly to a Daily Administration of Vitamin D3 Supplementation.

We aimed to determine whether a cumulative dose of vitamin D3 produces the same effects on the serum concentration of 25(OH)D3 if it is given daily or monthly. This is a monocentric, two-armed, randomized, interventional, open, and parallel study conducted from November 2016 to March 2017 in Belgium. We randomized 60 subjects with vitamin D deficiency to receive 2000 IU vitamin D3 daily or 50,000 IU monthly. The same cumulative dose of vitamin D3 was given to each treatment group (150,000 IU). The 25(OH)D3 serum concentrations from baseline to day 75 were 14.3 ± 3.7 to 27.8 ± 3.9 ng/mL in the monthly group and 14.1 ± 3.4 to 28.8 ± 5.4 ng/mL in the daily group. The mean change versus the baseline level was significantly different between the groups at day 2, 4, 7, and 14 and no longer different from day 25. One day after the intake of vitamin D3, as expected, serum 25(OH)D3 and 1,25(OH)2D3 increased significantly in the monthly group, whereas they did not change significantly in the daily group. The median time to reach the 20 ng/mL target concentration was significantly different in the two groups, in favor of the monthly regimen (1 day versus 14 days; p = 0.02). In conclusion, a monthly administration of 50,000 IU vitamin D3 provides an effective tool for a rapid normalization of 25(OH)D3 in deficient subjects. A daily administration of the same cumulative dose is similarly effective but takes two weeks longer to reach the desirable level of 20 ng/mL.

Skeletal health in breast cancer survivors.

Although some risk factors for breast cancer might be protective for osteoporosis, several cross-sectional studies have reported, nevertheless, that patients with breast cancer have a lower bone mass and potentially a higher incidence of fractures than expected. In any case, it appears that patients with breast cancer are not protected from osteoporosis, which provides further support for the recommendation that bone health is assessed after a diagnosis of breast cancer. Most adjuvant therapies will lead to increased bone loss and a higher fracture rate. Among the adjuvant therapy options for premenopausal patients with breast cancer, endocrine therapy (ovarian suppression) and chemotherapy can result in cancer treatment-induced bone loss (CTIBL) of up to 10% at the lumbar spine after one year. Antiresorptive therapies prevent CTIBL in premenopausal women with breast cancer. Most of the evidence demonstrating the efficacy of bisphosphonates in the prevention of CTIBL is derived from clinical trials with zoledronic acid. The addition of zoledronic acid 4mg per six months to adjuvant endocrine therapy maintained and even increased bone mass during a 3-year treatment period and significantly improved disease-free survival in a population of young women who underwent menopause due to the adjuvant treatment. The major contributor to bone loss in the adjuvant treatment of breast cancer in postmenopausal women is the use of aromatase inhibitors (AIs). Oncology trials have underestimated the fracture risk in the setting of AI-induced bone loss. In the ABCSG-18 study, the only trial in which fracture incidence was the primary endpoint, the rate of clinical fractures was close to 10% after 3 years in the placebo group on AIs only. Bisphosphonates and denosumab at osteoporosis treatment doses can counteract AI-induced bone loss. In the ABCSG-18 trial, treatment with denosumab 60mg injection every 6 months reduced the risk of first clinical fracture relative to placebo by 50%. Current guidelines recommend antiresorptive therapy in patients with a baseline T score of <-2.0 or with two or more clinical risk factors for fracture. These recent guidelines will need to be updated, as similar significant protective effects were seen in women with either normal or low bone mass. Moreover, a formal meta-analysis of individual patient data from more than 18,000 women in 26 randomized trials of adjuvant zoledronic acid or clodronate treatment for early breast cancer revealed that bisphosphonates significantly reduced the risk of first distant recurrence in bone and the risk of breast cancer mortality, at least in postmenopausal women. Even though the increased risk of fracture during adjuvant treatment for breast cancer in postmenopausal women is notable, an enhanced risk of fracture in long-term survivors of breast cancer remains under debate. The most recent studies suggest that Caucasian breast cancer survivors do not have a significantly increased risk of osteoporotic fracture over the long term.

Vitamin D and osteosarcopenia: an update from epidemiological studies.

PURPOSE OF REVIEW: The review summarizes recent epidemiological studies that examined the relationship between osteoporosis and sarcopenia to assess the impact of vitamin D status or supplementation on health outcomes related to these two medical conditions. RECENT FINDINGS: Osteoporosis and sarcopenia are major public health problems, but whether these two diseases should be considered alone or combined into a single condition is not clear. No consensual definition of osteosarcopenia is largely accepted. Most observational studies demonstrate some relationship between muscle and bone health. Vitamin D status is generally lower in study participants with bone or muscle wasting. Studies on the effects of vitamin D supplementation on muscle or bone health have provided conflicting results, likely because of the heterogeneity between studies. However, the most positive results were observed in study participants with low vitamin D status and in studies that avoided massive boluses of vitamin D. SUMMARY: More observational and interventional studies are needed to confirm the exact role of vitamin D in the pathophysiology and treatment of osteosarcopenia.

[Hypercalcemia and inactive mutation of CYP24A1. Case-study and literature review]. / Hypercalcémie par mutation inactivatrice du CYP24A1. Étude d'un cas et revue de la littérature.

We present the case of a family whose members have high levels of serum calcium (hypercalcaemia) by loss of function of the enzyme vitamin D 24-hydroxylase due to bi-allelic mutations in the CYP24A1 gene: c.443 T>C (p.Leu148Pro) and c.1187 G>A (p.Arg396Gln). 24-VITD hydroxylase is a key player in regulating the circulating calcitriol, its tissue concentration and its biological effects. Transmission is recessive. The estimated prevalence of stones in the affected subjects is estimated between 10 and 15%. The loss of peripheral catabolism of vitamin D metabolites in patients with an inactivating mutation of CYP24A1 is responsible for persistent high levels of 1,25-dihydroxyvitamin D especially after sun exposure and a charge of native vitamin D. Although there are currently no recommendations (French review) on this subject, this disease should be suspected in association with recurrent calcium stones with nephrocalcinosis, and a calcitriol-dependent hypercalcaemia with adapted low parathyroid hormone levels. Resistance to corticosteroid therapy distinguishes it from other calcitriol-dependent hypercalcemia. A ratio of 25-hydroxyvitamin D/24.25 hydroxyvitamin D>50, is in favor of hypercalcemia with vitamin D deficiency 24-hydroxylase. Genetic analysis of CYP24A1 should be performed at the second step. The current therapeutic management includes the restriction native vitamin D supplementation and the limitation of sun exposure. Biological monitoring will be based on serum calcium control and modulation of parathyroid hormone concentrations.

Supplementation with 80,000 IU vitamin D3/month between November and April corrects vitamin D insufficiency without overdosing: Effect on serum 25-hydroxyvitamin D serum concentrations.

INTRODUCTION: Vitamin D insufficiency, defined by a 25-hydroxyvitamin D (25OHD) serum concentration<20ng/mL, is highly frequent in the French general population, especially between November and April. The aim of this study was to evaluate whether 80,000 IU vitamin D3 every month during this period of the year was able to maintain a 25OHD level between 20 and 60ng/mL in apparently healthy subjects whatever their basal vitamin D status. METHODS: Ninety-eight subjects volunteered to receive an 80,000 IU vitamin D3 dose every month between November 2014 and April 2015. Serum 25OHD, calcemia and calciuria were measured just before the first dose (Month 0), just before the 4th dose (M4), and one month after the 6th dose (M7). RESULTS: At M0, 25OHD was 17.5±9.5ng/mL. Sixty subjects (61.2%) had a 25OHD<20ng/mL and 25 (25.5%) had a 25OHD<10ng/mL. 25OHD increased significantly at M4 (35.3±8.0ng/mL) and M7 (40.1±8.5) without change in calcemia and calciuria. At M4, 2 subjects had a 25OHD slightly below 20ng/mL (17.6 and 19.7ng/mL), and none had a concentration>60ng/mL. At M7, all had a serum 25OHD>20ng/mL and 2 subjects had a value slightly above 60ng/mL (62.1 and 63.2ng/mL). CONCLUSION: A monthly supplementation with 80,000 IU vitamin D3 between November and April corrected vitamin D insufficiency in subjects in whom it was initially very frequent, without overdosing. This protocol is simple, safe and costless, and can be easily implemented when physicians detect risk factors for hypovitaminosis D in patients for whom a 25OHD measurement is not indicated.

Impact of the type of dialysis membranes on the circulating concentration of markers of vitamin D metabolism.

INTRODUCTION: Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend vitamin D supplementation in hemodialyzed patients to monitor 25(OH)-vitamin D 25(OH)D levels. However, patient-to-patient inconsistency can be observed in response to the treatment. In this study, we aimed to evaluate the impact of the dialysis membrane on 25(OH)D, albumin (Alb) and vitamin D-binding protein (VDBP), the major players of vitamin D transport and storage. MATERIAL AND METHODS: Alb (Cobas), VDBP (R&D) and 25(OH)D (liquid chromatography-tandem mass spectrometry) were measured in 75 patients before and after a 4-hour dialysis session. Ten dialysis membranes were used: FX10, FX80, FX800, BK-2.1F, BG-2.1U, Rexeed 15 A, Rexeed 21 A, TS 1.8 SL and TS 2.1 SL manque la ELISIO 21H. Accordingly, 13 patients were dialyzed with membranes possessing high adsorption and high cut-off properties (BK), 17 with membranes possessing high adsorption but usual cut-off properties (BG) and all the remaining 45 patients with polysufone (PS) membranes with usual adsorptive and cut-off properties. Among these 45 patients treated with PS, we compared those treated by classical dialysis (HD) (n = 14) and hemodiafiltration (HDF) (n = 31). Results were corrected for total extracellular volume to take into consideration the hemoconcentration after dialysis. RESULTS: The 3 analytes showed a decreased concentration after the dialysis session. The decrease of ALB, VDBP and 25(OH)D was similar with the adsorptive (BG) and PS membranes. However, patients treated with adsorptive and high cut-off membrane (BK) presented a significantly higher decrease values of Alb (-9.6%[-15.1; -7.5]), of VDBP (-20.6%[-36.6; -17.2] and 25(OH)D (-17%[-27.3; -12.3]) compared to other membranes (BG and PS).When we limited our study to PS membranes, we did not observe any significant difference between the HD or HDF modalities in the decrease for any of the studied parameters. CONCLUSIONS: A significant loss of Alb, VDBP and 25(OH)D occurs after a dialysis session. This loss is significantly more important when patients are dialyzed with high adsorption and high cut-off dialysis membranes.