Serum 25-Hydroxyvitamin D in Obese Spanish Adults: the Camargo Cohort Study

Objectives

To describe the 25(OH)D status in Spanish obese postmenopausal women and men ≥?50 years, to compare their results with those of the overweight or normal weight population, and to determine whether differences are observed between both sexes and with seasonal variation throughout the year.

Patients and Methods

We studied 2597 subjects (1826 postmenopausal women and 771 men ≥?50 years). Serum concentrations of 25(OH)D, intact parathyroid hormone (PTH), aminoterminal propeptide of type I collagen (PINP), and C-terminal telopeptide of type I collagen (CTX) were determined by electrochemiluminiscence (Elecsys 2010, Roche). Bone mineral density (BMD) was measured by DXA. Participants were divided according to body mass index (BMI) groups (normal ≥?20 and <?25 kg/m², overweight ≥?25 and?<?30 kg/m², or obese ≥?30 kg/m²).

Results

Obese people had lower serum 25(OH)D values (20.9?±?8.2 ng/ml) than overweight (23.3?±?8.8 ng/ml; p?<?0.0001) or normal-weight subjects (24.4?±?8.9 ng/ml; p?<?0.0001). They have also lower levels of both PINP and CTX. In contrast, PTH concentrations and BDM values were higher in obese individuals. When stratifying by sex, the difference in serum concentration of 25(OH)D remained significant in women, but not in men, persisted throughout the year, and was inversely correlated with BMI and waist circumference.

Conclusions

Despite lower serum 25(OH)D concentrations and higher PTH levels, obese and overweight women have higher lumbar spine and hip BMD and lower bone remodeling markers than normal weight women, suggesting that low serum 25(OH)D levels do not negatively affect bone health.

     

Vitamin D deficiency and seasonal variation over the years in São Paulo,Brazil

Summary

Brazil is a tropical/subtropical geographic area with elevated ultraviolet (UV) radiation. We report very high prevalence of vitamin D deficiency in a large database of Brazilian subjects and show seasonal and reciprocal relationship between vitamin D and parathyroid hormone (PTH) over the years in this tropical area.

Introduction

We aim to examine the prevalence of vitamin D deficiency, characterize the temporal relationship between 25-hydroxyvitamin D levels (25(OH)D) and intact PTH (iPTH) according to seasons, and investigate potential associations between 25(OH)D levels and extra-skeletal outcomes in a Brazilian population.

Methods

We retrospectively determined population weekly mean concentrations of unpaired 25(OH)D and iPTH using 39,004 laboratory results of Brazilian individuals of both genders aged 2 to 95 years. The 25(OH)D and iPTH distributions were normalized, and the means fit with a sinusoidal function. Potential associations between 25(OH)D serum levels and inflammatory markers, fasting glucose, HbA1c and Homeostasis Model Assessment index (HOMA) were examined.

Results

Of the samples, 33.9 % had 25(OH)D serum concentrations lower than 20 ng/mL, while the vast majority (70.7 %) were found to be vitamin D deficient or insufficient (<30 ng/mL). Vitamin D deficiency was significantly higher during the winter as compared to the summer (38.4 % <20 ng/mL and 75.5 % <30 ng/mL versus 23.3 % <20 ng/mL and 62.5 % <30 ng/mL, respectively; p?<?0.001). Seasonal variation was observed for both 25(OH)D and iPTH. 25(OH)D peaks occurred in March and troughs in September. iPTH levels showed an inverted pattern of peaks and troughs with a delay of 1?±?5 week. 25(OH)D was significantly associated with inflammatory markers but not with glucose homeostasis.

Conclusions

A sinusoidal interrelationship has been detected between vitamin D and PTH in this tropical population. A large percentage of the individuals showed vitamin D deficiency. Public health strategies are needed to better understand and manage this very high and apparently contradictory prevalence of vitamin D deficiency.

     

Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays

Summary

A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D.

Introduction

This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations.

Methods

DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21–80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D.

Results

Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r _s?=?0.02, p?=?0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p?<?0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (?0.34, p?<?0.001) versus free/bioavailable 25(OH)D (?0.18/?0.24 depending on DBP assay, p?≤?0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites.

Conclusions

The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health.

     

Low serum 25-hydroxyvitamin D is associated with increased risk of stress fracture during Royal Marine recruit training

Summary

The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training. Poor vitamin D status was associated with an increased risk of stress fracture. Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status.

Introduction

Stress fracture is a common overuse injury in military recruits, including Royal Marine (RM) training in the UK. RM training is recognised as one of the most arduous basic training programmes in the world. Associations have been reported between serum 25-hydroxyvitamin D (25(OH)D) and risk of stress fracture, but the threshold of 25(OH)D for this effect remains unclear. We aimed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training.

Methods

We prospectively followed 1082 RM recruits (males aged 16–32 years) through the 32-week RM training programme. Troops started training between September and July. Height, body weight and aerobic fitness were assessed at week 1. Venous blood samples were drawn at weeks 1, 15 and 32. Serum samples were analysed for 25(OH)D and parathyroid hormone (PTH).

Results

Seventy-eight recruits (7.2 %) suffered a total of 92 stress fractures. Recruits with a baseline serum 25(OH)D concentration below 50 nmol L^?1 had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold (χ² ₍₁₎?=?3.564, p?=?0.042; odds ratio 1.6 (95 % confidence interval (CI) 1.0–2.6)). Baseline serum 25(OH)D varied from 47.0?±?23.7 nmol L^?1 in February, to 97.3?±?24.6 nmol L^?1 in July (overall mean 69.2?±?29.2 nmol L^?1, n?=?1016). There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 (r?=??0.209, p?<?0.001) and week 32 (r?=??0.214, p?<?0.001), but not at baseline.

Conclusion

Baseline serum 25(OH)D concentration below 50 nmol L^?1 was associated with an increased risk of stress fracture. Further studies into the effects of vitamin D supplementation on stress fracture risk are certainly warranted.

     

Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort

Background

Vitamin D plays an important role in the mineral and bone disorder seen in chronic kidney disease (CKD). Deficiency of 25-hydroxyvitamin D (25OHD) is highly prevalent in the adult CKD population.

Methods

The prevalence and determinants of 25OHD deficiency (defined as a level <20 ng/ml) were examined longitudinally in 506 children in the CKiD cohort. Predictors of secondary hyperparathyroidism and the determinants of 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels were also evaluated.

Results

Deficiency of 25OHD was observed in 28 % of the cohort at enrollment. Significant predictors of 25OHD deficiency were older age, non-white race, higher body mass index, assessment during winter, less often than daily milk intake, non-use of nutritional vitamin D supplement and proteinuria. Lower values of glomerular filtration rate (GFR), serum 25OHD, calcium and higher levels of FGF23 were significant determinants of secondary hyperparathyroidism. Lower GFR, low serum 25OHD, nephrotic-range proteinuria, and high FGF23 levels were significant determinants of serum 1,25(OH)₂ D levels.

Conclusions

Deficiency of 25OHD is prevalent in children with CKD and is associated with potentially modifiable risk factors such as milk intake, nutritional vitamin D supplement use, and proteinuria. 25OHD deficiency is a risk factor for secondary hyperparathyroidism and decreased serum 1,25(OH)₂D in children with CKD.

     

Serum 25-hydroxyvitamin D level and diabetic nephropathy in patients with type 2 diabetes mellitus

Objective

Patients with chronic kidney disease have a very high prevalence of deficiency of 25-hydroxyvitamin D [25(OH)D]. We evaluate the association between 25(OH)D and diabetic nephropathy (DN) in a Chinese sample with type 2 diabetes mellitus.

Method

The subjects were patients with diabetes mellitus who were hospitalized at our hospital during the period from June 2012 to July 2014. Serum levels of 25(OH)D were tested at admission. DN was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g in a random spot urine sample. Multivariate analyses were performed using logistic regression models.

Results

We found that serum 25(OH)D levels were significantly lower in diabetes with DN as compared to without DN [8.5 (IQR 6.8–11.3) vs. 13.9 (IQR 11.2–18.2) ng/ml, P < 0.0001]. Based on the ROC curve, the optimal cutoff value of serum 25(OH)D levels as an indicator for diagnosis of DN was projected to be 10.5 ng/ml, which yielded a sensitivity of 82.6 % and a specificity of 72.7 %, with the area under the curve at 0.807 [95 % confidence interval (CI) 0.764–0.849]. Multivariate logistic regression analysis adjusted for common risk factors showed that with serum 25(OH)D level ≤10.5 ng/ml was an independent indicator of DN [odds ratio (OR) = 6.559; 95 % CI 2.864–11.368].

Conclusions

Our findings suggested that diabetes with DN had lower serum 25(OH)D levels and that determination of 25(OH)D statuses might be used to identify patients at increased risk of developing nephropathy complications.

     

Accentuated hyperparathyroidism in type II Bartter syndrome

Background

Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described.

Methods

We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n?=?14) or Barttin-deficient type IV BS (n?=?20).

Results

Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6?±?85.8 vs. 92.5?±?48 pg/ml in BS-IV, p?=?0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19?±?0.71 vs. 0.01?±?1.04 in BS-IV, p?<?0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63?±?1.25 vs. 4.36?±?0.98, p?=?0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group.

Conclusions

PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II.

     

Are radiographic indices reliable indicators for quantitative bone mineral density and vitamin D status after femoral neck fractures? A retrospective study in 112 elderly patients

Background

Radiographic parameters and indices obtained from hip x-rays are a potential tool to promptly estimate bone quality in elderly hip fracture patients. Preoperative decision in whether to use cemented or cement augmented implants might be supported by this information and thus improve patient safety. Subsequently, this study was conducted to evaluate radiographic parameters as a prescreening tool for bone quality.

Methods

A retrospective analysis of 112 elderly patients with a femoral neck fracture after low-energy trauma was performed (81 % female, 19 % male). Three radiological indices were calculated on hip x-rays: cortical index antero-posterior CTI (ap), cortical index lateral CTI (lat) and canal to calcar ratio CCR. These indices were analyzed for correlations with DXA T-Scores and serum 25-hydroxyvitamin D (25(OH)D) using the Spearman test.

Results

Median age of patients was 80 (IQR 72–86) years. A linear correlation was found for CTI (lat) and T-Score at the total hip (p?<?0.001, r?=?0.589), femoral neck (p?=?0.005, r?=?0.405) and the lumbar spine (p?=?0.002, r?=?0.299). A significant correlation was also indicated between CTI (lat) and 25(OH)D (p?=?0.002, r?=?0.293). CTI (lat) at a cut-off level of 0.4 showed a sensitivity of 79 % and a specificity of 56 % in predicting a T-score?≤??2.5 at the total hip. Gender specific analysis revealed a higher sensitivity (100 %) and specificity (73 %) of CTI (lat) at a cut-off level of 0.4 for men. For severe vitamin D deficiency (<10 ng/ml) sensitivity and specificity were 75 % and 65 %.

Conclusion

Radiographic indices as the CTI (lat) exhibit a direct correlation to BMD and serum 25OH vitamin D levels. A CTI (lat) cut-off level of 0.4 is recommended for identifying patients at risk of osteoporosis expressed by T-Scores?≤??2.5 and severe vitamin D deficiency.

     

Vitamin D Deficiency Before Bariatric Surgery: Should Supplement Intake Be Routinely Prescribed?

Background

Before bariatric surgery, we demonstrate a 96% rate of vitamin D deficiency in morbidly obese French patients: should supplement intake be routinely prescribed? We conducted a prospective observational study to demonstrate the prevalence of vitamin D deficiency in morbidly obese patients awaiting bariatric surgery.

Methods

Clinical and biological data were collected on 50 successive patients.

Results

Data showed vitamin D deficiency in 96% (25-OH vitamin D = 31 ± 13 nmol/l), with a cut-point of 50 nmol/l. Secondary hyperparathyroidism was found in 44% of patients with hypovitaminosis D (parathyroid hormone (PTH), 59?±?24 pg/ml). Impaired PTH level concerned 89% of this group, considering the cut-point at 30 pg/ml. No significant correlation appeared between vitamin D and calcium or phosphate levels.

Conclusions

Before surgery, we demonstrated a higher incidence of vitamin D deficiency in morbidly obese French patients as compared to the general population. The incidence was also higher than previous American studies. Screening for hypovitaminosis D may routinely be considered in morbid obesity. Long-term observation is, however, needed to assess the advantages and potential side effects of systematic vitamin D supplements.

     

25-Hydroxycholecalciferol response to single oral cholecalciferol loading in the normal weight,overweight, and obese

Summary

After a single cholecalciferol load, peak serum 25-hydroxycholecalciferol (25OHD) is lower in individuals with a higher body mass index (BMI), probably due to it being distributed in a greater volume. Its subsequent disappearance from the serum is slower the higher the individual’s BMI, probably due to the combination of a larger body volume and a slower release into the circulation of vitamin D stored in adipose tissue.

Introduction

The aim of the study is to examine 25-hydroxycholecalciferol (25OHD) response to a single oral load of cholecalciferol in the normal weight, overweight, and obese.

Methods

We considered 55 healthy women aged from 25 to 67 years (mean?±?SD, 50.8?±?9.5) with a BMI ranging from 18.7 to 42 kg/m² (mean?±?SD, 27.1?±?6.0). The sample was divided into three groups by BMI: 20 were normal weight (BMI?≤?25 kg/m²), 21 overweight (25.1?≤?BMI?≤?29.9 kg/ m²), and 14 obese (BMI?≥?30 kg/m²). Each subject was given 300,000 IU of cholecalciferol orally during lunch. A fasting blood test was obtained before cholecalciferol loading and then 7, 30, and 90 days afterwards to measure serum 25OHD, 1,25 dihydroxyvitamin D [1,25 (OH)₂D], parathyroid hormone (PTH), calcium (Ca), and phosphorus (P). Participants’ absolute fat mass was measured using dual energy X-ray absorptiometry (DEXA).

Results

The fat mass of the normal weight subjects was significantly lower than that of the overweight, which in turn was lower than that of the obese participants. Serum 25OHD levels increased significantly in all groups, peaking 1 week after the cholecalciferol load. Peak serum 25OHD levels were lower the higher the individuals’ BMI. After peaking, the 25OHD levels gradually decreased, following a significantly different trend in the three groups. The slope was similar for the overweight and obese, declining significantly more slowly than in the normal weight group. In the sample as a whole, there was a weakly significant negative correlation between fat mass and baseline 25OHD level, while this correlation became strongly significant at all time points after cholecalciferol loading.

Conclusions

The lower peak 25OHD levels seen in the obese and overweight is probably due to the cholecalciferol load being distributed in a larger body volume. The longer persistence of 25OHD in their serum could be due to both their larger body volume and a slower release into the circulation of the vitamin D stored in their adipose tissue.

     

Cholecalciferol Injections Are Effective in Hypovitaminosis D After Duodenal Switch: a Randomized Controlled Study

Background

By treating obesity, one of the major epidemics of this past century, through bariatric surgery, we may cause complications due to malnourishment in a growing population. At present, vitamin D deficiency is of interest, especially in patients with inferior absorption of fat-soluble nutrients after biliopancreatic diversion with duodenal switch (BPD/DS).

Methods

Twenty BPD/DS patients, approximately 4 years postoperatively, were randomized to either intramuscular supplementation of vitamin D with a single dose of 600,000 IU cholecalciferol, or a control group. Patients were instructed to limit their supplementation to 1400 IU of vitamin D and to avoid the influence of UV-B radiation; the study was conducted when sunlight is limited (December to May).

Results

Despite oral supplementation, a pronounced deficiency in vitamin D was seen (injection 19.3; control 23.2 nmol/l) in both groups. The cholecalciferol injection resulted in elevated 25[OH]D levels at 1 month (65.4 nmol/l), which was maintained at 6 months (67.4 nmol/l). This resulted in normalization of intact parathyroid hormone (PTH) levels. No changes in vitamin D or PTH occurred in the control group.

Conclusions

In BPD/DS patients, having hypovitaminosis D despite full oral supplementation, a single injection of 600,000 IU of cholecalciferol was effective in elevating vitamin D levels and normalizing levels of intact PTH. The treatment is simple and highly effective and thus recommended, especially in cases of reduced UV-B radiation.

     

The vitamin D status in ankylosing spondylitis in relation to intestinal inflammation,disease activity,and bone health: a cross-sectional study

Summary

We assessed the vitamin D status in ankylosing spondylitis (AS) patients and healthy controls in the late winter when no vitamin D is produced by the sunlight. The vitamin D status was often poor, but not lower in AS and not associated with disease activity or signs of gut inflammation.

Introduction

The aims of the study were to investigate the vitamin D levels attained mainly by dietary intake in ankylosing spondylitis (AS) in comparison with healthy controls and in relation to gut inflammation, measured indirectly by fecal calprotectin, disease activity, osteoproliferation, bone mineral density (BMD), and vertebral fractures.

Methods

Serum 25-hydroxy vitamin D (25(OH)D) was measured in 203 AS patients and 120 healthy controls at the end of “the vitamin D winter,” when the out-door UVB irradiation is too low to allow synthesis of vitamin D₃ in the skin at the latitude of Gothenburg, Sweden. Fecal calprotectin was measured in stool samples. Disease activity was assessed with CRP, ESR, ASDAS_CRP, BASDAI, BAS-G, BASFI, and BASMI. Lateral spine radiographs were scored for osteoproliferation and vertebral fractures using the mSASSS and Genant scores. BMD was measured in the lumbar spine and femoral neck.

Results

Vitamin D insufficiency (a serum 25(OH)D <50 nmol/L) was found in approximately 50 % of the AS patients, but serum 25(OH)D was not different from healthy controls and not significantly correlated with fecal calprotectin, gastrointestinal symptoms, disease activity parameters, mSASSS, BMD, or vertebral fractures.

Conclusions

The vitamin D status was often poor in the late winter in AS but not different from the healthy controls. No evidence for a connection between subclinical gut inflammation, malabsorption, and hypovitaminosis D was found. Serum 25(OH)D was not associated with disease activity, osteoproliferation, BMD, or vertebral fractures. We suggest that the lower vitamin D levels in AS, previously found by others, may be caused by reduced out-door UVB exposure.

     

Undiagnosed Primary Hyperparathyroidism and Recurrent Miscarriage: The First Prospective Pilot Study

Background

Primary hyperparathyroidism (pHPT) in pregnancy is reported to be associated with significant maternal and foetal complications and an up to threefold increase in the risk of miscarriage. However, the true incidence of pHPT in pregnancy, complete and miscarried, is unknown and there are no data on the prevalence of undiagnosed pHPT in recurrent miscarriage (RM) (≥3 consecutive miscarriages under 24-week gestation). This is the first prospective study aiming to establish the prevalence of undiagnosed pHPT in RM.

Methods

Following UK National ethics committee approval, women who had experienced 3 or more consecutive miscarriages were recruited from a nationwide RM clinic. Serum corrected calcium, phosphate, PTH and vitamin D were evaluated. Patients with raised serum calcium and/or PTH were recalled for confirmatory tests. Power calculations suggested that a minimum of 272 patients were required to demonstrate a clinically significant incidence of pHPT.

Results

Three hundred women were recruited, median age 35 years (range 19–42). Eleven patients had incomplete data, leaving 289 patients suitable for analysis; 50/289 patients (17%) with abnormal tests were recalled. The prevalence of vitamin D deficiency (<25 nmol/l) and insufficiency (25–75 nmol/l) was 8.7 and 67.8%, respectively. One patient was diagnosed with pHPT (0.34%) and underwent successful parathyroidectomy.

Conclusions

The prevalence of undiagnosed pHPT (0.34%) in RM in this study appears to be many times greater than the 0.05% expected in this age group. The findings of this pilot study merit follow-up with a larger-scale study. Routine serum calcium estimation is not currently undertaken in RM and should be considered.

     

Changes in Bone Mineral Density Following Weight Loss Induced by One-Anastomosis Gastric Bypass in Patients with Vitamin D Supplementation

Background

Little is known about changes in bone mineral density (BMD) following weight loss after one-anastomosis gastric bypass (OAGB) and the role of serum vitamin D and its supplementation on bone metabolism. We evaluated BMD after OAGB as a function of vitamin D supplementation with respect to a minimum threshold of 25-hydroxy-vitamin-D [25(OH)D] concentration, which could prevent or decelerate an eventual bone loss.

Methods

Fifty bariatric patients who participated in the randomized controlled trial were included in this analysis. BMD and anthropometric measurements by DXA and laboratory parameters were assessed before (T0), at 6 (T6), and 12 months (T12) after surgery.

Results

OAGB resulted in a 36% total body weight loss with a decrease in body fat and an increase in lean body mass. A significant decrease in BMD was seen in lumbar spine by 7%, left hip 13%, and total body 1%, but not in forearm. Bone turnover markers increased significantly but with normal parathyroid hormone concentrations. Weight loss was not associated with changes in BMD. A serum 25(OH)D concentration?>?50 nmol/l at T6 and T12 (adequate-vitamin-D-group; AVD) showed a significant lower bone loss, compared to the inadequate-vitamin-D-group (IVD; <?50 nmol/l). Lower bone loss in the left hip showed a strong correlation with higher 25(OH)D concentrations (r?=?0.635, p?=?0.003).

Conclusion

These findings support a dose effect of vitamin D supplementation on bone health and suggest that 25(OH)D concentrations need to be above 50 nmol/l at least during the first postoperative year to decelerate bone loss in patients undergoing OAGB.

Clinical Trial Registry Number and Website

Clinicaltrials.gov (NCT02092376) at https://clinicaltrials.gov/.EudraCT (2013-003546-16) at https://eudract.ema.europa.eu/.

     

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study

Background

Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20–100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation.

Methods

Multicenter longitudinal study of children (2–18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later.

Results

Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D?<?20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D?<?20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p?<?0.01) in children supplemented with vitamin D.

Conclusions

In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2–4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

     

Associations of total and free 25OHD and 1,25(OH)<Subscript>2</Subscript>D with serum markers of inflammation in older men

Summary

Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.

Introduction

Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.

Methods

We tested serum total 25OHD, total 1,25(OH)₂D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)₂D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.

Results

IL-6 was lower in men with higher 25OHD (?0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) ?0.07 to ?0.38 μg/mL) and with higher 1,25(OH)₂D (?0.20 μg/mL, 95 % CI ?0.0004 to ?0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)₂D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)₂D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)₂D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)₂D).

Conclusions

Associations of 1,25(OH)₂D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)₂D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

     

Is there an association between low serum 25-OH-D levels and the length of hospital stay in orthopaedic patients after arthroplasty?

Background

The purpose of this observational study was to evaluate serum levels of 25-OH-D in patients scheduled to undergo elective hip or knee arthroplasty. We hypothesised that 25-OH-D level is an independent risk factor for length of stay in orthopaedic patients after elective hip or knee arthoplasty.

Materials and methods

25-OH-D levels were measured in 1083 patients admitted to an orthopaedic surgery department to undergo elective hip or knee arthroplasty. Comparisons were performed using Chi square or Student’s t test, followed by univariate and multiple linear regression analysis examining the correlation between the length of stay in the orthopaedic department and 25-OH-D level while adjusting for possible confounders.

Results

Overall, 86 % of patients had insufficient serum levels of 25-OH-D, and over 60 % were vitamin D deficient. The mean length of stay was 13.2 ± 8.3 days. In patients with hypovitaminosis D, the length of stay was significantly longer compared to patients with normal serum 25-OH-D levels (15.6 ± 7.2 compared to 11.3 ± 7.9 days, P = 0.014). In univariate analyses, serum 25-OH-D level was inversely related to the length of stay in our orthopaedic department compared to patients with normal vitamin D levels (r = ?0.16; P = 0.008). In multivariate analyses, the length of stay remained significantly associated with low 25-OH-D levels (P = 0.002), indicating that low vitamin D levels increase the length of stay.

Conclusions

We found a high frequency of hypovitaminosis D among orthopaedic patients scheduled to undergo elective arthroplastic surgery. Low vitamin D levels showed a significant inverse association to the length of stay in our orthopaedic department. Patients with vitamin D levels in the target range were hospitalised 4.3 days less than patients with hypovitaminosis D.Level 3 of evidence according to “The Oxford 2011 levels of evidence”.

     

Prevalence of vitamin D insufficiency among adolescents and its correlation with bone parameters using high-resolution peripheral quantitative computed tomography

Summary

Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents.

Introduction

The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents.

Methods

Three hundred thirty-three girls and 230 boys (12–16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed.

Results

Sixty-four point seven percent and 11.4 % of subjects were insufficient [25?≤?25(OH)Vit-D?≤?50 nmol/L] and deficient [25(OH)Vit-D?<?25 nmol/L] in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7?±?13.6 and 35.9?±?12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels.

Conclusion

Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.

     

Effect of concomitant vitamin D deficiency or insufficiency on lumbar spine volumetric bone mineral density and trabecular bone score in primary hyperparathyroidism

Summary

Lower vitamin D and higher parathyroid hormone (PTH) levels are associated with higher volumetric BMD and bone strength at the lumbar spine as measured by central quantitative computed tomography in primary hyperparathyroidism (PHPT), but there are no differences in bone microarchitecture as measured by trabecular bone score (TBS).

Introduction

The purpose of this study was to evaluate the association between 25-hydroxyvitamin D (25OHD) and volumetric bone mineral density (vBMD) and the TBS at the lumbar spine (LS) in PHPT.

Methods

This is a cross-sectional analysis of PHPT patients with and without low 25OHD. We measured vBMD with quantitative computed tomography (cQCT) and TBS by dual-energy X-ray absorptiometry (DXA) at the LS in 52 and 88 participants, respectively.

Results

In the cQCT cohort, those with lower vitamin D (<20 vs. 20-29 vs. ≥30 ng/ml) tended to be younger (p?=?0.05), were less likely to use vitamin D supplementation (p?<?0.01), and had better renal function (p?=?0.03). Those with 25OHD <20 ng/ml had 80 and 126 % higher serum PTH levels respectively vs. those with 25OHD 20–29 ng/ml (p?=?0.002) and 25OHD ≥30 ng/ml (p?<?0.0001). Covariate-adjusted integral and trabecular vBMD were higher in those with 25OHD 20–29 vs. those with 25OHD ≥30 ng/ml, but those with 25OHD <20 did not differ. Because there were few participants with 25OHD deficiency, we also compared those with vitamin D <30 vs. ≥30 ng/ml. Covariate-adjusted integral and trabecular vBMD were 23 and 30 % higher respectively (both p?<?0.05) in those with vitamin D <30 vs. ≥30 ng/ml. TBS was in the partially degraded range but did not differ by vitamin D status.

Conclusion

In mild PHPT, lower 25OHD is associated with higher PTH, but vitamin D deficiency and insufficiency using current clinical thresholds did not adversely affect lumbar spine skeletal health in PHPT. Further work is needed to determine if higher vBMD in those with lower vitamin D is due to an anabolic effect of PTH.