25-OH Vitamin Research Articles

P-14 A case of Paget's disease of bone presenting at early stages of life

Abstract Paget's disease of bone is the metabolic bone disease that affects 2-4% of individuals over age 55 in European nations. The disease may be asymptomatic and can be detected incidentally through x-rays or biochemical tests conducted for another condition. It can also manifest as bone pain, deformity, fracture, Here, we present a case of Paget's bone disease that manifested at a young age. A 47-year-old female was referred to an endocrinology outpatient clinic due to a nonfunctional pituitary gland microadenoma. She has had constant pain in the right thigh region for the past two years, and no fractures have ever been reported. During the physical examination, the patient's right femur was sensitive to palpation. The results of the standard laboratory test were as follows: Creatinine: 0.61 mg/dl (0-1.2 mg/dl), Albumin: 50 g/L (35-52 g/L), Calcium: 9.8 mg/dl (8.8-10.6 mg/dl), Phosphorus: 4.2 mg/dl (2.6-4.5 mg/dl), PTH (Parathyroid Hormone): 33 ng/L (15-65 ng/L), Alkaline Phosphatase: 524 U/L (33-98 U/L) and 25-OH vitamin D is 43.7 mcg/L. A bone scintigraphy was performed due to the patient's elevated alkaline phosphatase levels and bone pain. The scintigraphy revealed elevated osteoblastic activity in a sclerotic lesion expanding the right femoral cortex, and the results were reported in accordance with Paget's disease. A biopsy of the right femur lesion was performed due to the patient's young age and to rule out other diagnosis such as osteosarcoma or bone metastases. The pathology results revealed thickened and distinct cement lines along with calcified bone fragments, consistent with Paget's disease. The patient was administered 5 mg of IV zoledronic acid, and the alkaline phosphatase level was determined to be 123 U/L (Reference Range: 33-98) at the one-month control following treatment. Paget's disease can be diagnosed in young people. Therefore, it is important to take into account even a slight increase in ALP levels that is linked to early radiological abnormalities.

Vitamin D Levels among Chronic Kidney Disease Patients at a Tertiary Care Hospital: A Cross-sectional Study

Introduction: In patients with Chronic Kidney Disease (CKD), a high prevalence of metabolite abnormalities has been observed. Numerous studies have demonstrated that individuals with reduced Glomerular Filtration Rate (GFR) are more susceptible to severe vitamin D deficiency compared to those with normal kidney function. Aim: To investigate the association between vitamin D levels and the severity of CKD among patients at Siddhartha Medical College, GGH in Vijayawada, Andhra Pradesh, India. Materials and Methods: The present hospital-based cross- sectional study was conducted at Siddhartha Medical College, GGH, Vijayawada, Andhra Pradesh, India from December 2021 to February 2022. A total of 100 CKD patients with a GFR of less than 60 mL/min/1.72 m2 were included in the study. Vitamin D levels were assessed using Chemiluminescence immunoassay (Access 2, Beckman Coulter), and vitamin D deficiency was defined as 25-OH vitamin D levels of less than 10 ng/mL, while insufficiency was defined as levels between 10 to 30 ng/mL. Statistical analysis was performed using Analysis of Variance (ANOVA) test and Pearson’s correlation test. Results: The mean age of the study population was 53.25±7.6 years, with the majority (32%) belonging to the 51-60 years age group. In terms of gender distribution, approximately three-fourths (72%) of the subjects were male. Hypertension was present in 44% of CKD patients, diabetes in 38%, and cardiovascular disease in 38%. Total 53% of CKD patients were classified as stage 4 on the Kidney Disease: Improving Global Outcome (KDIGO) CKD staging. Vitamin D deficiency was observed in 26% of patients, while 39% had insufficiency. A statistically significant association was found between the severity of CKD staging and mean vitamin D levels, with lower mean levels observed in stages 4 and 5. Conclusion: Vitamin D deficiency was present in one-fourth of the CKD patients, and it was more pronounced in advanced stages of CKD.

THE INDEPENDENT EFFECTS OF TYPE 2 DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE ON BONE TURNOVER MARKERS.

Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are associated with disturbed mineral homeostasis and serum bone biomarkers. The interplay between T2DM and CKD on serum bone turnover markers (BTM) is unclear. Our aim was to describe the BTM in patients with T2DM, CKD or both. In this observational, single-centre, prospective study, we included 320 patients over 40 years, divided into four groups: T2DM and normal kidney function (n=142), T2DM and CKD (n=36), CKD and normal glucose metabolism (n=29) and healthy controls (n=113). We excluded patients treated for osteoporosis and with secondary osteoporosis. Patients were compared by age, levels of glycated hemoglobin, PTH, alkaline phosphatase, osteocalcin (OC), CTx and 25 OH vitamin D. Univariate analysis showed that GFR correlated significantly with PTH (r=0.37), OC (r=0.43) and CTX (r=0.45) in the diabetes group but only with PTH (r=0.34) in the non-T2DM group. Multivariate analysis showed that GFR remained significantly correlated with the same bone markers even after adjustment for age, sex or 25(OH)D levels. Diabetics seem to have lower levels of alkaline phosphatase (68±22.1 U/L) and CTX (0.37±0.24 ng/mL) than those without diabetes (76.7±29.6. U/L and 0.5±0.19 ng/mL, respectively). There was no correlation between BTM and glycated hemoglobin. Bone turnover markers correlate with GFR, particularly in patients with T2DM. However, alkaline phosphatase is lower in T2DM than in non-T2DM.

The serum-ascites vitamin D gradient: a diagnostic marker for spontaneous bacterial peritonitis in Egyptian cirrhotic patients

Background The most prevalent infectious consequence of liver cirrhosis is spontaneous bacterial peritonitis (SBP). Ascitic fluid polymorph nuclear neutrophils (PMN) counts of more than 250 cells/µL are used as the gold standard for diagnosing SBP. Patients with decompensated cirrhosis also had significantly decreased serum 25-OH vitamin D levels compared with controls. Aim Our aim is to investigate the role of (serum ascites vitamin D gradient) as a diagnostic factor for diagnosis of SBP. Patients and method This cross-sectional study included 80 cirrhotic ascitic patients from Egypt who were treated at the hospitals affiliated with the Tropical Medicine and Infectious Diseases Department at Tanta University. Group 1: 40 ascitic patients with SBP. Group 2: 40 ascitic patients without SBP History taking, clinical examination, laboratory analysis, and imaging studies were applied to every patient. Results Child-Pugh score was significant in both groups as child C was significantly higher in group 1 than group 2. Total leucocyte count and differential neutrophil were significantly higher in group 1 than group 2 while child B was higher in group 2 than group 1. Differential lymphocyte was significantly lower in group 1 than group 2. SADG was significantly lower in group 1 than group 2. SADG ratio can significantly predict SBP (P = 0.036 and AUC = 0.632) at cut-off less than or equal to −25.8 with 37.50% sensitivity, 95.00% specificity, 88.2% positive predictive value (PPV), and 60.3% negative predictive value (NPV). Conclusion Patients with cirrhotic ascites had decreased SADG and higher SBP. In these cases, it might be used as a diagnostic and prognostic marker for SBP. Patients with decompensated cirrhosis, independent of SBP, have an increased prevalence of vitamin D insufficiency.

ОСТЕОПЕНИЯ КАК ПРОЯВЛЕНИЕ ИДИОПАТИЧЕСКОЙ ГИПЕРКАЛЬЦИУРИИ У ДЕТЕЙ

Idiopathic hypercalciuria (IH) can lead to the development of osteopenia and osteoporosis in childhood. Vitamin D and its receptor, encoded by the VDR gene, play a major role in maintaining normal calcium levels in bone tissue. The purpose of the study: to study the state of bone mineral density in children with idiopathic hypercalciuria and the association of vitamin D receptor (VDR) gene polymorphisms with osteopenia. Materials and methods. The study included 35 children with IH aged 5 to 17 years with a history of fractures and/or decompensated caries. The children were subjected to X-ray densitometry to calculate the Z score in the lumbar spine and proximal femurs. A group of children with IH (n=20) underwent a study of the level of 25-OH vitamin D in blood plasma and a genetic study for the presence in genetic polymorphisms of the VDR gene: BsmI Polymorphism IVS10+283G>A, A-3731G (Cdx2), FokI Polymorphism; Ex4+4T>C. Results. A decrease in BMD was detected in 68.6% of children with IH, while 2 patients aged 15 and 17 years had signs of osteoporosis. The homozygous Ex4+4 CC genotype of the VDR (Fokl) gene was significantly more common in patients with idiopathic hypercalciuria. For the remaining genotypes of the VDR enzyme gene, no statistically significant differences could be detected (p>0.05). Conclusion. Idiopathic hypercalciuria in children often leads to a decrease in bone mineral density, which should be taken into account when treating children with this pathology. A genetic predictor of osteopenia in children with IH may be the carriage of the homozygous genotype (rare allele) Ex4+4 CC of whose VDR (Fokl) gene, the study can be used for early diagnosis and prevention of the development of osteoporosis.

VITAMIN D, CALCIUM, AND PHOSPHORUS STATUS IN CHILDREN WITH SPINA BIFIDA

Introduction. Children with spina bifida (SB) are at the highest risk of developing vitamin and mineral deficiencies, including vitamin D, due to a sedentary lifestyle, prolonged indoor stays, and dietary peculiarities. The aim of our study was to determine the dietary intakes of vitamin D, calcium, and phosphorus in children with spina bifida and the concentration of these nutrients in the serum of children with SB. Materials and Methods. The study included 20 children aged 2 to 17 years with congenital neural tube defect (spina bifida). The control group consisted of 67 healthy children aged 6 to 17 years. To determine the dietary intakes of vitamin D, calcium and phosphorus, children or their parents were surveyed using a questionnaire containing questions about the amount of consumption of certain food products over the week. The total amount of vitamin D, calcium, and phosphorus in the weekly diet were calculated, as well as their average daily intakes with food and overall. The concentration of 25-OH vitamin D, calcium, and phosphorus in the blood serum was determined using an enzyme immunoassay. Results. Among the examined children with SB, girls predominated (70.0%). Physical development delay and undernutrition were identified in 3 (15.0%), overweight - in 6 (30.0%) children. Most children with SB exhibited clinical manifestations of mineral metabolism disorders: body proportion disturbances (55.0%), posture disorders (40.0%), scoliosis and/or chest deformity (50.0%), caries (40.0%). Despite the presence of dairy, meat, and fish products in the weekly diet of all children with SB, their quantity was insufficient to meet the daily needs for vitamin D, calcium, and phosphorus. Inadequate intake of vitamin D from food occurred in 70.0% of children, calcium deficiency in 90.0%, phosphorus deficiency in 80.0%, with the alimentary provision of calcium and phosphorus in children with SB being significantly lower than in healthy children (p=0.0027 and p=0.0047, respectively). Optimal levels of vitamin D in the blood serum were observed in only 10.0% of children with SB, which was twice less than in healthy children, while its deficiency was observed 1.5 times more often in children with SB than in healthy children. Half of the patients with SB had reduced calcium levels, and 70.0% had reduced phosphorus levels. Conclusions. The study results demonstrate a wide prevalence of vitamin D deficiency and insufficiency (in 90.0%), calcium and phosphorus deficiency in children with SB, indicating the need for additional intake of these nutrients alongside dietary and lifestyle corrections. Further research on a larger cohort of patients with supplementation regimens is necessary to reduce the risk of complications and improve the quality of life for children with SB.

Associations of vitamin D receptor gene polymorphism with idiopathic hypercalciuria in children

Introduction. Idiopathic hypercalciuria (IH) is one of the most common metabolic disorders in children and can lead to the development of urolithiasis over childhood. In this regard, studying the etiology of this pathological condition will help to prevent the development of IH and reduce the risk of developing urolithiasis.
 Study purpose: to study the role of genetic polymorphisms of the VDR gene in the development of IH in children and their relatives of the first and second lines of kinship.
 Materials and methods. The study included 68 people, including 35 children aged of 3 to 17 years with identified hypercalciurine and 33 first- and second-line relatives with IH and urolithiasis. A study of the level of 25-OH vitamin D in blood plasma and a genetic study for the presence of polymorphisms of the vitamin D receptor gene VDR were carried out including: BsmI Polymorphism IVS10+283G>A, A-3731G (Cdx2), FokI Polymorphism; Ex4+4T>C. To compare the frequency of occurrence of vitamin D receptor (VDR) genotypes, samples of conditionally healthy individuals permanently residing in Kemerovo and natives of the European part of the Russian Federation were taken. At the same time, for the VDR G283A (BsmI) gene, a healthy sample consisted of 232 people from Kemerovo and 96 cases from the European part of Russia, for the VDR A-3731G gene — 269 and 243 people, and for the VDR FokI TC gene — 172 and 96 people, respectively. 
 Results. Reducing the content of 25(OH)D in the blood of less than 30 ng/ml was detected in 33 (48.5%) IH children. 25 (OH)D level below 20 ng/ml was detected in 15 (22.1%) patients. In IH patients and level 25(OH)D in the blood of less than 20 ng/ml, the homozygous variant 283 GG of the VDR gene (BsmI) was found in 20% of the examined versus 51% (p = 0.028) of conditionally healthy individuals. The heterozygous genotype of 283 PA of the VDR gene (BsmI) was determined in 73.3% of IH patients versus 41.7% of conditionally healthy individuals (p = 0.027). The heterozygous Ex4+4TC genotype of the VDR Fokl gene was recorded in 66.7% of the examined IH patients and low serum vitamin D levels (< 20 ng/ml) when compared with the level in conditionally healthy individuals (p = 0.030). In patients with low vitamin D levels against IH background, the proportion of the minor allele A 283 of the VDR gene (BsmI) was determined significantly more often than in healthy individuals (p = 0.044).
 Conclusion. A relationship was identified between polymorphism of the vitamin D receptor gene VDR (polymorphic marker BsmI (rs1544410) of the VDR gene 283G>A; polymorphic marker Fokl (rs2228570) of the VDR gene Ex4+4T>C) with IH and deficiency of 25(OH)D levels in the blood serum of children.

Evaluation of serum gamma-glutamyl transferase among patients with coronary artery disease in Erbil city

Background and objective: The leading cause of morbidity and mortality globally is coronary artery disease (CAD). One of the recent new parameters for evaluating CAD is Serum GGT, which has been shown to be a predictor of coronary artery status irrespective of the traditional cardiovascular risk variables. This study aimed to evaluate and assess the correlation between serum GGT and other variables among patients with CAD in comparison with healthy subjects. Methods: A case-control prospective study. Subjects were grouped into Group I (CAD patients-117 individuals) and Group II (healthy Subjects-83 individuals) based on their Coronary Angiographic profile at surgical specialty Hospital-Cardiac Center-Erbil/Iraq. Parameters of S. GGT, S. total cholesterol, S.HDL-C, S.LDL-C, S. VLDL-C, and S.TG, S. (25)OH vitamin D, serum troponin T, S.CK-MB, and CRP were assessed for both groups. Results: The study population included 58% of male and 42% of female participants, with an age range of 30-77, with a mean of 56.13± 10.5 years old. The Pearson’s correlation coefficient of serum GGT with other variables showed that the relation between serum GGT with VLDL-C, CRP, and Triglyceride among CAD patients was found to be a weakly positive correlation and statistically significant (r=0.3, P = 0.004), (r=0.2, P = 0.031), and (r=0.3, P = 0.007) respectively. Conclusion: The present study showed that S.GGT as a new potential biochemical marker for preclinical atherosclerosis, would be a useful and important marker for assessing and evaluating risk factors of coronary artery disease and to further evaluations for CAD.

Prospective study of the effects of isotretinoin and vitamin D levels on severe acne vulgaris.

Acne vulgaris (AV) is a common inflammatory skin condition associated with psychological and social distress. Its pathogenesis involves factors such as sebaceous hypersecretion and Cutibacterium acnes colonization. Vitamin D plays a crucial role in the pathogenesis of various inflammatory skin disorders, including AV, due to its immunomodulatory effects and involvement in keratinocyte growth and maturity. However, adequate sun exposure is required for optimal vitamin D synthesis. Isotretinoin (IOS), a vitamin A derivative, is a commonly used medication for severe acne, acting by binding to retinoid receptors. It can also form heterodimers with vitamin D receptors, potentially increasing vitamin D catabolism. Previous studies examining the impact of oral IOS on serum vitamin D levels have yielded inconsistent results. Therefore, this study aimed to assess changes in 25-hydroxy (OH) vitamin D serum levels in individuals with severe AV before and after IOS treatment. One hundred patients with severe AV were enrolled, each receiving 0.75 mg/kg IOS treatment daily for 4 months. Serum 25 OH vitamin D levels were measured before, during, and after treatment. This study found a significant increase in serum 25 OH vitamin D levels among patients with severe AV following IOS treatment (p < 0.001). This study suggests that AV may negatively impact vitamin D synthesis, but IOS treatment appears to raise vitamin D serum levels in individuals with severe AV. Further research is needed to confirm the potential relationship between AV and vitamin D levels.

Multicenter comparison of analytical interferences of 25-OH vitamin D immunoassay and mass spectrometry methods by endogenous interferents and cross-reactivity with 3-epi-25-OH-vitamin D3

BackgroundVitamin D (vit-D) deficiency is highly prevalent in the Korean population, highlighting the need for accurate measurements. In this study, the interferences by endogenous and cross-reactive substances were compared between routine vit-D immunoassays and mass spectrometry (MS) methods. MethodsTwo MS methods and 4 immunoassays from different manufacturers (Abbott, Beckman Coulter, Roche, Siemens) were compared. Residual samples that were icteric, lipemic, hemolyzed, high in rheumatoid factor, from myeloma patients, or patients undergoing hemodialysis were collected. Also, 4 levels of National Institute of Standards and Technology (NIST) Standard Reference Material 972a, and 12 samples serially spiked with 3-epi-25-OH-D3 were prepared. ResultsSignificant interferences were observed in hemolytic (Roche), icteric (Beckman and Siemens) and lipemic samples (all 4 immunoassays). Level 4 NIST material and 3-epi-25-OH-D3-spiked samples induced significant cross-reactivity, yielding higher total vit-D measurements in non-epimer-separating MS methods, and both the Beckman and Roche immunoassays. ConclusionMost observed interferences were consistent with manufacturers’ claims, but overall improvement of immunoassay bias limits is required. Awareness of potential interference is important to increase the accuracy of vit-D measurements. Moreover, care is due when interpreting vit-D results of newborns, infants and less commonly, pregnant women, who are known to have physiologically high levels of the highly cross-reactive 3-epi-25-OH-D3.

Using Machine Learning to Identify the Relationships between Demographic, Biochemical, and Lifestyle Parameters and Plasma Vitamin D Concentration in Healthy Premenopausal Chinese Women.

Vitamin D plays a vital role in maintaining homeostasis and enhancing the absorption of calcium, an essential component for strengthening bones and preventing osteoporosis. There are many factors known to relate to plasma vitamin D concentration (PVDC). However, most of these studies were performed with traditional statistical methods. Nowadays, machine learning methods (Mach-L) have become new tools in medical research. In the present study, we used four Mach-L methods to explore the relationships between PVDC and demographic, biochemical, and lifestyle factors in a group of healthy premenopausal Chinese women. Our goals were as follows: (1) to evaluate and compare the predictive accuracy of Mach-L and MLR, and (2) to establish a hierarchy of the significance of the aforementioned factors related to PVDC. Five hundred ninety-three healthy Chinese women were enrolled. In total, there were 35 variables recorded, including demographic, biochemical, and lifestyle information. The dependent variable was 25-OH vitamin D (PVDC), and all other variables were the independent variables. Multiple linear regression (MLR) was regarded as the benchmark for comparison. Four Mach-L methods were applied (random forest (RF), stochastic gradient boosting (SGB), extreme gradient boosting (XGBoost), and elastic net). Each method would produce several estimation errors. The smaller these errors were, the better the model was. Pearson's correlation, age, glycated hemoglobin, HDL-cholesterol, LDL-cholesterol, and hemoglobin were positively correlated to PVDC, whereas eGFR was negatively correlated to PVDC. The Mach-L methods yielded smaller estimation errors for all five parameters, which indicated that they were better methods than the MLR model. After averaging the importance percentage from the four Mach-L methods, a rank of importance could be obtained. Age was the most important factor, followed by plasma insulin level, TSH, spouse status, LDH, and ALP. In a healthy Chinese premenopausal cohort using four different Mach-L methods, age was found to be the most important factor related to PVDC, followed by plasma insulin level, TSH, spouse status, LDH, and ALP.

The association between maternal vitamin D deficiency and postpartum hemorrhage and uterine atony.

Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide. There are several known risk factors for postpartum hemorrhage related to pregnancy and delivery, but less evidence of predisposing factors. Recent research has shown that vitamin D deficiency may increase the risk of cesarean section due to dystocia, based on its effect on striated muscle as well as possible effect on the myometrium. Whether vitamin D deficiency increases the risk for postpartum hemorrhage and especially atonic hemorrhage is unknown. This was a retrospective translational study. The study population included 1367 women in Sweden and the main exposure was the serum concentration of 25-hydroxylated vitamin D at time of delivery. The LIASON® 25 OH vitamin D total assay method was used for analyzing 25-hydroxylated vitamin D. Vitamin D insufficiency was defined as serum concentration <50 nmol/L and vitamin D deficiency as serum concentrations <25 nmol/L. Primary outcomes were postpartum hemorrhage and severe postpartum hemorrhage defined as bleeding ≥500 mL and ≥ 1000 mL, respectively 2 h after delivery. Secondary outcome was atonic postpartum hemorrhage. Crude and adjusted odds ratios were calculated with 95% confidence intervals using univariable and multivariable logistic regression. Three different adjustment methods were used, adjusting for maternal, obstetrical and neonatal confounders. Postpartum hemorrhage and severe postpartum hemorrhage afflicted 31.3% and 6.4% of the women, respectively. Rate of atonic postpartum hemorrhage was 21% in the whole population. Rate of vitamin D insufficiency and deficiency was 57%. Vitamin D insufficiency or deficiency was neither found to be associated with postpartum hemorrhage, nor with atonic postpartum hemorrhage. In this study, the vitamin D status of women at the time of delivery was not a predictor of postpartum hemorrhage overall or atonic postpartum hemorrhage.

Serum concentrations of 25-OH vitamin D and the pro-inflammatory interleukins IL-17, IL-23, and IL-18 in patients with plaque psoriasis.

The present study aimed to assess vitamin D status and serum concentrations of pro-inflammatory cytokines IL-17, Il-23, and IL-18 in patients with chronic plaque psoriasis and their association with various demographic and clinical characteristics. The study was conducted during the autumn/winter period on 48 patients with chronic plaque psoriasis and 48 controls. Total serum 25(OH)D level was determined with Roche Elecsys® 2010 Vitamin D total assay. Commercial ELISA kits were used for quantifying the serum levels of IL-17A, IL-18, and IL-23. Serum 25(OH)D had a median value of 16.95 ng/mL (IQR 10.8-23.50) for patients with psoriasis and 18.80 ng/mL (IQR 15.45-25.85) for the control group (P=0.09). A moderate negative correlation was found between PASI score and 25(OH)D levels (rs=-0.34; P=0.02). The serum levels of IL-17 (P=0.001), IL-23 (P=0.01) and IL-18 (P=0.02) were significantly higher in the patient group compared to controls. IL-17 concentrations were higher in patients with moderate to severe psoriasis compared to patients with mild psoriasis (P=0.003). No significant correlations were detected between the serum concentrations of 25(ОH)D and IL-17, IL-23, and IL-18. It was confirmed that IL-17 serum level is associated with psoriasis severity. Measurement of 25(OH)D serum concentration can be useful in patients with moderate to severe psoriasis with or without comorbidities. A direct association between 25(OH)D serum concentration and the serum concentrations of IL-17, IL-23, or IL-18 was not identified in this study.

Indices of sarcopenic obesity are important predictors of finite element analysis-derived bone strength in older adults with obesity.

The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT). One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m2) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using μFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement. Both ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R 2=0.301 to 0.448, HGS: R 2=0.346 to 0.472, FM%: R 2=0.299 to 0.432) (p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05). These findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy.

High Incidence of Vitamin D Deficiency Among Patients Undergoing Hematopoietic Stem Cell Transplant and a Single Ultra-High Dose Vitamin D Replacement

Introduction: Vitamin D involves in several important human physiologic pathways from bone metabolism to inflammation and immune regulation. Patients who undergo hematopoietic stem cell transplant (HSCT) are at risk of developing vitamin D deficiency from various mechanisms and replacement of vitamin D in these patients can be challenging according to several reasons. In addition, vitamin D may potentially affect outcomes, overall health and quality of life after HSCT. An ultra-high dose vitamin D replacement was previously explored in pediatric HSCT patients but has never been investigated in adult patient population. In this study, we explored the incidence of vitamin D deficiency, the safety and efficacy of a single ultra-high dose vitamin D replacement including its effect on bone health among adult patients with hematologic malignancy undergoing HSCT. Patients and Methods: First, we looked at the retrospective cohort of patients who underwent HSCT between January 2017 and August 2022 to explore the incidence of vitamin D deficiency (25-hydroxy vitamin D level &amp;lt;20 ng/mL) in Thailand. Subsequently, we prospectively included adult patients with hematologic malignancy undergoing both autologous (ASCT) and allogeneic HSCT (alloHSCT) from September 2022 to June 2023. All patients received a single ultra-high dose vitamin D on the day of admission prior to the initiation of conditioning regimens. We reported the safety and efficacy of a single ultra-high dose vitamin D (Ergocalciferol; Vitamin D2) replacement as calculated by weight and pre-transplantation vitamin D level among these patients using the Stoss protocol previously described. The effect of an ultra-high dose vitamin D on bone turnover was also monitored. Results: In the retrospective cohort, 229 patients underwent HSCT (146 ASCT and 83 alloHSCT). Vitamin D deficiency was observed in 147 patients (64.6%) including 91 (62.3%) ASCT and 56 (67.5%) alloHSCT. The median 25-hydroxy (25-OH) vitamin D level was 17.6 (4.0-86.3) ng/mL comparable between autologous and allogeneic patients. In the prospective cohort, 45 patients underwent HSCT (27 ASCT and 18 alloHSCT). The median age of patients at the time of HSCT was 49 (23-67) years with 18 patients (40%) being male. The median pre-transplant 25-OH vitamin D level was 20.2 ng/mL with 22 patients (48.9%) (13 ASCT, 9 alloHSCT) meeting the criteria of vitamin D deficiency. The median dose of vitamin D2 used was 500,000 (300,000-600,000) IU. At day +28 post-HSCT, 40% of patients were able to attain 25-OH vitamin D level above 30 ng/mL comparable between ASCT and alloHSCT but significantly higher compared to the retrospective cohort. The time to neutrophil and platelet engraftment were 13 (9-26) days and 14 (9-33) days, comparable between the controlled retrospective cohort and high dose replacement prospective cohort. The median levels of parathyroid hormone (PTH) and bone turnover markers including osteocalcin, β-CrossLaps (β-CTx), and procollagen type I N-propeptide (PINP) at day+28 was 45.4 (19.4-152.2) pg/mL, 11.3 (6.0-16.8) ng/mL, 0.79 (0.1-13.0) ng/ml and 43.7 (19.7-133.7) mcg/L, respectively. Among patients who underwent alloHSCT, the incidence of cytomegalovirus reactivation and acute graft versus host disease was 72.2% and 11.1% (no grade 3-4), respectively. Figure 1 shows the kinetic of serum 25-OH vitamin D, Calcium, β-CTx and PINP of patients in the prospective cohort from baseline to day +28 post-HSCT. At all timepoints (day 0, +7, +14, +21, +28), the median level of vitamin D level was significantly higher whereas the median serum PINP level was significantly lower compared to the baseline level. There was no occurrence of hypercalcemia or bony events during the time of the study. Conclusion: Our study highlights a high incidence of vitamin D deficiency in HSCT patients. Utilizing a single ultra-high dose vitamin D is an effective and safe approach to replace vitamin D in adult patients undergoing HSCT. A high percentage of patients could maintain adequate vitamin D level during post-transplant period. PINP level was sustainably decreased after vitamin D replacement indicating a lower bone resorption. Whether this approach will translate into improved immune function, long-term bone health and outcomes compared to the conventional replacement strategy warrants further exploration in prospective randomized clinical trials.

Biological variation of plasma 25-Hydroxyvitamin D3, Serum vitamin B12, folate and ferritin in Turkish healthy subject

Biological variation (BV) plays a crucial role in determining analytical performance specifications, assessing serial measurements of individuals, and establishing the use of population-based reference intervals. Our study aimed to calculate the BV and BV-based quality goals of 25-hydroxyvitamin D3 (25-OH D3), ferritin, folate and vitamin B12 tests. We included a total of 22 apparently healthy volunteers (9 women and 13 men) aged 18-55 years in the study that we conducted in Turkey. Blood samples were collected from the participants once a week for five weeks. Serum ferritin, folate and vitamin B12 levels were measured using immunochemical method, while plasma 25-OH D3 levels were determined using the high-performance liquid chromatography method. Analysis of variance (ANOVA) was used to estimate analytical variation(CVA), within-subject BV(CVI) and between-subject BV(CVG). The individuality index (II) and reference change value (RCV) were calculated based on these data. The CVI of 25-OH D3, ferritin, folate, and vitamin B12 were found to be 1.8% (0.6%-2.5%), 16.9% (14.4%-20.2%), 10.7% (9.2%-12.7%), and 8.6% (6.8%-10.5%), respectively. CVG were 44.2% (34.3%-69.9%), 132% (87.7%-238%), 19.4% (14.4%-28.8%), and 39.6% (29.8%-59.0%) for the same biomarkers, while CVA were 3.2% (2.81%-3.71%), 3.5% (3.1%-4.1%), 4.0% (3.5%-4.6%), and 7.5% (6.6%-8.6%), respectively. The II values for 25-OH D3, ferritin, folate, and vitamin B12 were calculated as 0.04, 0.13, 0.55, and 0.22, respectively. The RCV were 10.2%, 47.8%, 31.7%, and 31.6%, respectively. Because the tests analyzed in this study exhibit high individuality, RCV should be preferred rather than population-based reference ranges in clinical interpretation of results.

Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria.

Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis. We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort. Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors. This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.

Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort

Mineral and bone disorder (MBD) in chronic kidney disease (CKD) is tightly linked to cardiovascular disease (CVD). In this study, we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular (CV) outcomes and mortality. In 5 217 participants of the German CKD (GCKD) study enrolled with an estimated glomerular filtration rate (eGFR) between 30–60 mL·min−1 per 1.73 m2 or overt proteinuria, serum osteoprotegerin (OPG), C-terminal fibroblast growth factor-23 (FGF23), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), cross-linked C-telopeptide of type 1 collagen (CTX1), procollagen 1 intact N-terminal propeptide (P1NP), phosphate, calcium, and 25-OH vitamin D were measured at baseline. Participants with missing values among these parameters (n = 971) were excluded, leaving a total of 4 246 participants for analysis. During a median follow-up of 6.5 years, 387 non-CV deaths, 173 CV deaths, 645 nonfatal major adverse CV events (MACEs) and 368 hospitalizations for congestive heart failure (CHF) were observed. OPG and FGF23 were associated with all outcomes, with the highest hazard ratios (HRs) for OPG. In the final Cox regression model, adjusted for CV risk factors, including kidney function and all other investigated biomarkers, each standard deviation increase in OPG was associated with non-CV death (HR 1.76, 95% CI: 1.35–2.30), CV death (HR 2.18, 95% CI: 1.50–3.16), MACE (HR 1.38, 95% CI: 1.12–1.71) and hospitalization for CHF (HR 2.05, 95% CI: 1.56–2.69). Out of the nine biomarkers examined, stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.

Is 25OH Vitamin D Excess before 36 Weeks Corrected Age an Independent Risk Factor for Bronchopulmonary Dysplasia or Death?

Low 25-Hydroxyvitamin D (25(OH)D) in preterm infants is a risk factor for bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate a beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and histological alterations in the lung evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120 nmol/L are also a risk factor for BPD or death. This retrospective single-center cohort study included only infants born at <31 weeks gestational age without major malformations with at least a determination of 25(OH)D at <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120 nmol/L (50.5% vs. 43.9%, p = 0.53). The logistic regression identified weight (OR 0.997, 95% CI [0.995-0.998]) and term (OR 0.737, 95% CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95% CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

Low serum 25‑hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis

BackgroundCognitive impairment frequently affects people with multiple sclerosis (MS). Low vitamin D has been associated with cognitive dysfunction in different neurodegenerative diseases, and, in MS, with motor disability and disease activity. We aim to investigate associations between vitamin D and cognitive status in MS. MethodsIn this cross-sectional study, we included 181 MS patients, recruited consecutively at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, between January and April 2022, with serum 25‑hydroxy (25-OH) vitamin D measurements using Chemiluminescence-ImmunoAssay, and cognitive assessment using the Brief International Cognitive Assessment for MS (BICAMS), which includes Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). We collected demographics (age, sex, education), and clinical variables (disease duration, disease subtype, expanded disability status scale (EDSS), disease modifying treatment, relapses in previous 12 months, vitamin D supplementation, comorbidities). For a subset of patients (n = 41, 23.2% of the total sample), we collected Beck Depression Inventory-II, Beck Anxiety Inventory, and Modified Fatigue Impact Scale. ResultsAt univariable linear regression models, serum 25-OH-vitamin D levels were 0.9 ng/mL higher for each unit increase of SDMT adjusted scores (Coeff=0.93; 95%CI=0.81, 1.04; p<0.01), 0.7 ng/mL higher for each unit increase of CVLT-II adjusted scores (Coeff=0.68; 95%CI=0.53, 0.83; p<0. 01), 0.6 ng/mL higher for each unit increase of BVMT-R adjusted scores (Coeff=0.58; 95%CI=0.43, 0.73; p<0.01), -9.63 ng/mL lower for each impaired BICAMS test (Coeff=-9.63; 95%CI=-11.48, -7.79; p<0.01), and -2.2 ng/mL lower for each unit increase of EDSS (Coeff=-2.16; 95%CI=-3.57, -0.75; p<0.01). At multivariable linear regression models, we confirmed associations between 25-OH-vitamin D and EDSS (Coeff=-2.09; 95%CI=-4.45, -0.43; p<0.01), SDMT (Coeff=0.75; 95%CI=0.60, 0.90; p<0.01), and CVLT-II (Coeff=0.14; 95%CI=0.01, 0.28; p = 0. 04). Results remained unchanged when including depression, anxiety and fatigue scores. ConclusionsLower serum 25-OH-vitamin D was associated with worse cognitive function in MS. Future studies should consider longitudinal variations in cognitive function in relation to vitamin D supplementation.