Association of race, body fat and season with vitamin D status among young women: a cross-sectional study

Objective The purpose of this study was to provide an estimate of vitamin D status in young women residing in south‐east Texas and to determine factors that predict 25‐hydroxyvitamin D (25‐OHD) concentration. Design A cross‐sectional study was conducted on 800 non‐Hispanic white, non‐Hispanic black, and Hispanic women 16–33 years of age, who were seen in an outpatient clinic. Measurements Information was obtained on race, smoking, exercise and dietary intake of vitamin D. Percentage total body fat (%TBF) was assessed using dual‐energy X‐ray absorptiometry (DXA). Exposure to sunlight was estimated by examining national records of temperature, hours of daylight and UV index for the latitude of the study site. To determine the relationship between 25‐OHD and %TBF, season, race, body mass index (BMI), dietary vitamin D, age and smoking in a multivariate context, stepwise linear regression analysis was performed. Results Serum 25‐OHD levels differed among the racial groups (all pairwise differences P < 0·001), with the lowest value among non‐Hispanic blacks (37·7 nmol/l) and the highest value among non‐Hispanic whites (71·8 nmol/l). Among Hispanics, mean serum 25‐OHD was 47·9 nmol/l. Serum 25‐OHD was negatively associated with %TBF (r = –0·28), BMF (r = –0·36) and TBF (r = –0·33), all P < 0·001, and positively associated with dietary vitamin D (r = 0·10) and pack years of smoking (r = 0·11), both P < 0·01. In the summer months, serum 25‐OHD values were higher (55·4 nmol/l) than in the winter months (48·1 nmol/l), P < 0·001. The final regression model predicting serum 25‐OHD levels included race, %TBF and season (all P < 0·05) and explained 36% of the variance in 25‐OHD. Conclusions Favourable environmental conditions do not result in sufficient vitamin D status for young women, especially non‐Hispanic blacks, Hispanics and the obese.     

Hypovitaminosis D and parathyroid hormone response in the elderly: effects on bone turnover and mortality

Objective To investigate whether absence of secondary hyperparathyroidism in the presence of hypovitaminosis D has altered bone turnover, fracture risk and mortality. Design A prospective cohort study. Patients A total of 1280 older men and women living in residential care facilities. Measurements We measured baseline serum 25‐hydroxyvitamin D (25OHD), serum intact PTH, serum amino‐terminal propeptide of type I collagen (PINP) and serum carboxy‐terminal telopeptide of type I collagen (CTX‐I). Deaths and fractures were recorded prospectively. Results Hypovitaminosis D (25OHD < 39 nmol/l) and absence of secondary hyperparathyroidism (PTH > 7·0 pmol/l) in the presence of hypovitaminosis D were common in this sample with a prevalence of 77·5% and 53·3%, respectively. In the presence of hypovitaminosis D, residents showing a hyperparathyroid response (n = 406) had significantly higher serum bone turnover markers than individuals with serum PTH levels ≤ 7·0 pmol/l (termed ‘low vitamin D, normal PTH’, n = 463). After adjusting for risk factors, mortality was significantly higher in the secondary hyperparathyroidism group than in the ‘low vitamin D, normal PTH’ group [hazard ratio (HR) = 1·35, 95% confidence interval (CI) 1·12–1·64; P = 0·002]. All residents with serum PTH levels ≤ 7·0 pmol/l (n = 603) were similar with regard to both bone turnover and mortality, independent of their actual vitamin D status. Conclusion Absence of secondary hyperparathyroidism in the presence of hypovitaminosis D appears to be common in the frail elderly and is associated with longer survival, similar to that observed in vitamin D‐replete elderly subjects.     

Predisposition to vitamin D deficiency osteomalacia and rickets in females is linked to their 25(OH)D and calcium intake rather than vitamin D receptor gene polymorphism

Background Osteomalacia (OSM) and rickets are widely prevalent in developing countries especially in females. The factors associated with such predisposition are not known. Objectives To identify nutritional, endocrine and genetic factors related to calcium and vitamin D metabolism that are associated with OSM/rickets in females. Subjects and methods We studied 98 patients with OSM or rickets and their relatives including male and female sibs and parents (n = 221) for the presence of biochemical OSM {low serum 25‐hydroxyvitamin D [25(OH)D], raised intact PTH (iPTH) and raised alkaline phosphatase} and associated nutritional and genetic factors. Polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) was used for genotyping vitamin D receptor (VDR) (BsmI and FokI) and PTH gene (BstBI and DraII) single nucleotide polymorphisms (SNPs) in 74 families. The differences in the factors associated with calcium and vitamin D among the different groups were analysed by analysis of variance (ANOVA). Logistic regression analysis and the transmission disequilibrium test (TDT) were carried out to assess association between nutritional and genetic factors, and the disease, respectively. Results Most of the patients were female (91·8%). The mean serum 25(OH)D level of the female patients was comparable to that of the female sibs (14·4 ± 5·7 vs. 18·3 ± 9·7 nmol/l). The frequency of biochemical OSM was fivefold higher in female than in male sibs (24·4%vs. 4·9%). Female sibs also had significantly lower 25(OH)D, dietary calcium intake and sunshine exposure than male sibs. The frequency of biochemical OSM was comparable between mothers and fathers. The odds of biochemical OSM in the family members was reduced by 11% per 15‐min daily sunshine exposure [odds ratio (OR) = 0·89, 95% confidence interval (CI) = 0·81–0·98, P = 0·02] and decreased by 20% per 100 mg dietary calcium intake (OR = 0·80, 95% CI = 0·67–0·96, P = 0·02). VDR/PTH gene SNPs showed no association with OSM/rickets on TDT analysis. Conclusion Among the immediate family members of patients with OSM/rickets, female sibs have features of biochemical OSM in up to 24·4%. Female sibs, unlike male sibs, share with patients features of markedly low serum 25(OH)D levels, poor dietary calcium intake and poor exposure to sunshine. Genetic factors such as VDR and PTH gene SNPs were not associated with OSM/rickets.     

Vitamin D deficiency in rural girls and pregnant women despite abundant sunshine in northern India

Context  Vitamin D deficiency is common in urban Indians despite living in the tropics and its public health consequences are enormous. However, 70% of India is rural, and data from rural subjects, who are expected to have good sun exposure, are scant.
Objectives  To determine the population prevalence of vitamin D deficiency in rural pregnant women and adolescent girls, compare serum 25-hydroxyvitamin D (25OHD) status in adolescent boys from the same families, and determine seasonal differences in serum 25OHD.
Design  A cross-sectional study conducted over 18 months.
Subjects  A random selection of 121 adolescent girls from a survey of a population of 8270 in a rural low socioeconomic community; 139 pregnant women in the second trimester; and a subset of 28 adolescent girls compared with 34 brothers.
Measurements  Serum 25OHD, serum alkaline phosphatase (AP), sun exposure, and dietary calcium intake.
Results  The age-adjusted community prevalence of vitamin D deficiency (25OHD < 50 nmol/l) in adolescent girls was 88·6%. Seventy-four per cent of pregnant women had vitamin D deficiency. Mean ± SD 25OHD in girls and women in summer was 55·5 ± 19·8 nmol/l compared to 27·3 ± 12·3 nmol/l in winter ( P  < 0·001). Winter serum 25OHD in boys (67·5 ± 29·0 nmol/l) was higher than that in their sisters (31·3 ± 13·5 nmol/l, P  < 0·001).
Conclusion  We report a high prevalence of vitamin D deficiency among pregnant women and adolescent girls from a rural Indian community. Boys are relatively protected. Seasonal variation in serum 25OHD is significant at latitude 26° N.     

Fatty fish and supplements are the greatest modifiable contributors to the serum 25-hydroxyvitamin D concentration in a multiethnic population

Objective Because vitamin D synthesis is lower in a heavily pigmented skin than in a lighter skin, the relative contribution of determinants to the vitamin D concentration might differ between ethnic groups. The aim of this study was to assess the prevalence of vitamin D deficiency and the relative contribution of vitamin D consumption and exposure to sunlight to the vitamin D concentration in a multiethnic population. Design Cross‐sectional study. Patients A total of 613 adults aged 18–65 years from a random sample from general practices in the Netherlands (52°N, 2003–05), stratified according to gender and ethnic group. Measurements Serum 25‐hydroxyvitamin D [25(OH)D], PTH, ethnic group, sunlight exposure, consumption of foods and supplements rich in vitamin D. Results The prevalence (95% confidence interval) of vitamin D deficiency [serum 25(OH)D < 25 nmol/l] was higher in Turkish (41·3%; 32·5–50·1), Moroccan (36·5%; 26·9–46·1), Surinam South Asian (51·4%; 41·9–60·9), Surinam Creole (45·3%; 34·0–56·6), sub‐Saharan African (19·3%; 9·1–29·5) and other adults (29·1%; 17·1–41·1) compared to the indigenous Dutch (5·9%; 1·3–10·5). Modifiable, significant determinants (standardized regression coefficients) for serum 25(OH)D concentration were: consumption of fatty fish (0·160), use of vitamin D supplements (0·142), area of uncovered skin (highest category 0·136; middle category 0·028), use of tanning bed (0·103), consumption of margarine (0·093) and preference for sun (0·089). We found no significant modification of ethnic group on the effect of sunlight determinants. Conclusion Of the modifiable determinants, fatty fish and supplements are the greatest contributors to the serum 25(OH)D concentration in a multiethnic population.     

ORIGINAL ARTICLE: Association between 25‐hydroxyvitamin D,somatic muscle weakness and falls risk in end‐stage renal failure

Objective Suboptimal levels of 25‐hydroxyvitamin D (25OHD) are common in haemodialysis patients (Chronic Kidney disease‐5D: CKD‐5D) and may be associated with reduced muscle strength and increased falls risk. We tested the hypothesis that 25OHD levels may be independently associated with falls risk in CKD‐5D. Background Supplementation with calcium and cholecalciferol reduces hip and other nonvertebral fractures in elderly individuals, and this effect may in part be attributable to reduction in falls frequency. The relationship between 25OHD and falls risk has not been investigated in CKD‐5D. Design and Patients This is a cross‐sectional study of 25 CKD‐5D patients with predialysis 25OHD, 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and intact parathyroid hormone (iPTH) measurement. Falls risk was assessed by quadriceps muscle strength, FallsScreen^© test (FST), Berg Balance Scale (BBS), timed ‘up and go’ (TUG) test, Modified Barthel Index (MBI) and Falls Efficacy Scale (FES). Results Mean age was 69·8 ± 12·1 years, and median time on dialysis was 3·1 years. Median 25OHD level was 55·3 nmol/l (range 20·8–125·8 nmol/l). Muscle strength was significantly positively correlated with 25OHD (P = 0·024) but not with 1,25(OH)₂D (P = 0·477) or PTH (P = 0·461). Statistically significant correlation between 25OHD levels and FST (P = 0·028) plus MBI (P = 0·0046) was noted. No significant correlation was detected between falls risk and 1,25(OH)₂D or PTH. Conclusions Suboptimal levels of 25OHD in CKD‐5D are associated with reduced quadriceps muscle strength and increased falls risk. 25OHD may be more important than the active renal metabolite 1,25(OH)₂D for muscle strength with implications for vitamin D choice and goals of supplementation. Further investigation is required to examine effectiveness of calciferol supplementation on the incidence of falls in CKD‐5D.     

Vitamin D, PTH and calcium levels in pregnant women and their neonates

Objectives To determine the prevalence of vitamin D deficiency in pregnant women and their neonates and to examine factors associated with vitamin D deficiency. Design and patients Population‐based study of pregnant women and their neonates from South‐eastern Sydney, Australia. Measurements Serum 25 hydroxy‐vitamin D (25‐OHD), PTH, calcium, albumin, phosphate and alkaline phosphatase were measured in women at 23–32 weeks gestation and on cord blood at delivery. Maternal skin phototype was recorded using the Fitzpatrick scale. Results Vitamin D deficiency (defined as 25‐OHD ≤ 25 nmol/l) was found in 144 of 971 (15%) women and 98 of 901 (11%) neonates. Median 25‐OHD was 52 nmol/l (range 17–174) in mothers and 60 nmol/l (17–245) in neonates. Maternal 25‐OHD levels varied by season, with lowest levels in late winter/early spring (P < 0·001). Factors associated with maternal vitamin D deficiency in multiple logistic regression were (OR, 95% CI): maternal birthplace outside Australia: 2·2 (1·4–3·5, P = 0·001), dark skin phototype: 2·7 (1·6–4·5, P < 0·001), wearing a veil: 21·7 (11·7–40·3, P < 0·001) and younger maternal age: 0·93 (0·89–0·97, P = 0·001). Maternal vitamin D deficiency increased the risk of neonatal vitamin D deficiency (OR 17·2, 95% CI 8·8–34·3) and birth weight was lower among infants of deficient vs. sufficient mothers: mean (SD) 3245 g (545) vs. 3453 g (555), P < 0·001. Conclusions Vitamin D deficiency is common among pregnant women; immigrant, veiled and dark skinned women are at greatest risk. Maternal vitamin D deficiency increases the risk of neonatal vitamin D deficiency and lower birth weight.     

Visfatin, low-grade inflammation and body mass index (BMI)

Objective Visfatin is an adipokine with revealing roles in inflammatory mechanisms but its implication in inflammation related to excessive adiposity/obesity is not studied yet. Our aim was to investigate the relations of visfatin with inflammation markers and body mass index (BMI) in the peripheral blood mononuclear cells (PBMCs), a type of cells closely related to inflammatory mechanisms. Design Cross‐sectional study, quantification of visfatin, TNF‐α, IL‐6 mRNA in PBMCs. Patients Eighty‐three supposed healthy individuals from the STANISLAS cohort, belonging in three BMI categories: BMI < 25 kg/m² (lean), 25 kg/m² ≤ BMI < 30 kg/m² (overweight) or BMI ≥ 30 kg/m² (obese). Measurements We measured visfatin gene expression (by real‐time quantitative PCR), in relation to gene expression of the pro‐inflammatory cytokines TNF‐α, IL‐6 in PBMCs and to anthropometric parameters (weight, BMI, waist : hip ratio), blood pressure, lipid profile, glucose and inflammatory markers (C‐reactive protein, lymphocyte count). Results Visfatin expression in PBMCs was significantly associated with BMI in a negative way (r = –0·21, P = 0·05). Global anova analysis test for lean and over‐weight/obese individuals showed a negative significant association between visfatin expression in PBMCs and BMI both for men and women (P = 0·05 and P = 0·01, respectively) and these associations remained significant after separating subjects in three groups (lean, overweight, obese) for men and women (P = 0·02 and P = 0·05, respectively). Correlation analysis between levels of expression of visfatin and TNF‐α showed a significant positive linear association (r² = 0·27, P < 0·0001). Conclusion These findings reveal a probable new role of visfatin in inflammation reflected in PBMCs, in the context of obesity.     

Vitamin D metabolites and skeletal consequences in primary hyperparathyroidism

Background Primary hyperparathyroidism (PHPT) is associated with reduced bone mineral density (BMD) mainly at sites rich in cortical bone. However, successful parathyroidectomy causes an increase in BMD especially at sites rich in trabecular bone. Plasma 25‐hydroxyvitamin D (25OHD) levels are typically reduced and plasma 1,25‐dihydroxyvitamin D [1,25(OH)₂D] slightly increased in PHPT. These variations in vitamin D metabolites may influence variations in BMD and fracture risk. Aim To investigate relations between preoperative vitamin D metabolites and skeletal consequences in patients with untreated PHPT and to appraise the influence of preoperative vitamin D metabolites on postoperative changes in BMD. Design Cross‐sectional and cohort study. Materials Two hundred and forty‐six consecutive Caucasian PHPT patients aged 19–91 years. (median 63, 87% females). Results BMD was reduced at the femoral neck (P < 0·001) and forearm (P < 0·001), but normal at the lumbar spine (P = 0·11). Levels of biochemical bone markers were associated with high plasma PTH, high plasma 1,25(OH)₂D and low plasma levels of 25OHD. Moreover, low plasma 25OHD was associated with low levels of BMD at the femoral neck (r_p = 0·23), the forearm (r_p = 0·19) and the whole body (r_p = 0·30), whereas plasma 1,25(OH)₂D was inversely associated with BMD at all regional sites and the whole body. Plasma PTH only showed an inverse association with BMD at the forearm (r_p = –0·21). No association was observed between biochemical variables and prevalent spinal fractures, all peripheral fractures or osteoporotic peripheral fractures. The annual increase in spinal BMD after surgery was positively associated with preoperative plasma PTH (r_p = 0·40), whereas the annual increase in whole body BMD was inversely associated with plasma 25OHD (r_p = –0·32). No change in BMD at the femoral neck and forearm was observed 1 year after surgery. Conclusion Low vitamin D status and high plasma 1,25(OH)₂D are associated with increased bone turnover and decreased BMD in patients with PHPT.     

Determinants of plasma PTH and their implication for defining a reference interval

Background To improve the diagnostic sensitivity of PTH measurements, more data on the upper limit of the reference interval for PTH levels were requested at a recent international consensus conference. As PTH levels vary inversely with plasma 25‐hydroxyvitamin D (25OHD) levels and as vitamin D insufficiency is widespread, particular attention should be given to the influence of low vitamin D levels on the PTH reference interval. Aim, design and methods In a cross‐sectional design, including 2316 women aged 17–84, we determined 95% reference interval using a nonparametric approach and studied the effects of potential predictors on plasma PTH levels. Results PTH was a positive function of age, body weight and BMI and inversely associated with total daily calcium intake, smoking, plasma calcium levels and 25OHD levels, all of which explained 16% of the variability in plasma PTH levels. The threshold value for 25OHD levels below which PTH levels started to rise was 82 nmol/l. Plasma PTH levels varied inversely with the seasonal variations in 25OHD levels. Mean PTH level was 4·1 pmol/l with a reference interval equal to 2·0–8·6 pmol/l. Restricting the population in whom the reference interval was calculated to only women with 25OHD levels above 30 or 100 nmol/l lowered the upper limit of the reference interval to 8·4 and 7·1 pmol/l, respectively. Similar, stratification according to age, body mass index, smoking and calcium intake had only minor impact on the reference interval. Conclusion Indices with known effects on plasma PTH levels have only a minor impact on the upper levels of the normative reference interval in women with intact renal function.     

Altered distribution of adiponectin isoforms in children with Prader-Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormones

Objective Prader–Willi syndrome (PWS) is a genetic syndrome characterized by relative hypoinsulinaemia and normal or increased insulin sensitivity despite profound obesity. We hypothesized that this increased insulin sensitivity is mediated by increased levels of total and high molecular weight adiponectin and associated with changes in levels of satiety hormones. Design, patients and measurements We measured total adiponectin and its isoforms [high molecular weight (HMW), middle molecular weight (MMW) and low molecular weight (LMW) adiponectin] and satiety hormones in 14 children with PWS [median age 11·35 years, body mass index (BMI) Z‐score 2·15] and 14 BMI‐matched controls (median age 11·97 years, BMI Z‐score 2·34). Results Despite comparable BMI Z‐scores and leptin levels, the PWS children exhibited lower fasting insulin and HOMA‐IR (homeostasis model assessment of insulin resistance) scores compared to obese controls. For any given BMI Z‐score, the PWS children showed higher concentrations of fasting total and HMW adiponectin and higher HMW/total adiponectin ratios. The HMW/total adioponectin ratio was preserved in children with PWS at high degrees of obesity. In PWS children, fasting plasma total adiponectin, HMW adiponectin and HMW/total adiponectin ratio correlated negatively with age (P < 0·05), HOMA‐IR (P < 0·01), BMI Z‐score (P < 0·05), insulin (P < 0·01) and leptin (P < 0·05). In addition to higher fasting ghrelin concentrations, the PWS children showed significantly higher fasting levels of total peptide YY (PYY) and gastric inhibitory polypeptide (GIP) compared to obese controls. Conclusions Relative to controls of similar age and BMI Z‐score, the PWS children had significantly higher levels of total and HMW adiponectin, and increased ratios of HMW/total adiponectin. These findings may explain in part the heightened insulin sensitivity of PWS children relative to BMI‐matched controls.     

A prospective study of the associations between 25‐hydroxy‐vitamin D,sarcopenia progression and physical activity in older adults

Objective Low 25‐hydroxyvitamin D (25OHD) levels may be associated with both sarcopenia (the age‐related decline in muscle mass and function) and low physical activity (PA). Our objective was to describe prospective associations between 25OHD, muscle parameters, and PA in community‐dwelling older adults. Design Prospective, population‐based study with a mean follow‐up of 2·6 ± 0·4 years. Patients Six hundred and eighty‐six community‐dwelling older adults (49% women; mean ± SD 62 ± 7 years old). Measurements Appendicular lean mass percentage (%ALM) and body fat assessed by Dual‐energy X‐ray Absorptiometry, leg strength by dynamometer, leg muscle quality (LMQ), PA assessed by pedometer, self‐reported sun exposure by questionnaire, and serum 25OHD measured by radioimmunoassay. Results Participants with 25OHD ≤50 nm had lower mean %ALM, leg strength, LMQ and PA (all P < 0·05). As a continuous function, baseline 25OHD was a positive independent predictor of change in leg strength (β = 5·74 kg, 95% CI 0·65, 10·82) and LMQ (β = 0·49 kg/kg, 95% CI 0·17, 0·82). Also, change in 25OHD was positively predicted by baseline %ALM (β = 2·03 pm /p.a., 95% CI 0·44, 3·62) leg strength (β = 0·30 pm /p.a., 95% CI 0·06, 0·53), LMQ (β = 4·48 pm /p.a., 95% CI 0·36, 8·61) and PA (β = 2·63 pm /p.a., 95% CI 0·35, 4·92) after adjustment for sun exposure and body fat. Conclusions 25OHD may be important for the maintenance of muscle function, and higher skeletal muscle mass and function as well as general PA levels may also be beneficial for 25OHD status, in community‐dwelling older adults.     

Vitamin D status, physical performance and body mass in patients surgically cured for primary hyperparathyroidism compared with healthy controls - a cross-sectional study

Objective Low plasma 25‐hydroxyvitaminD (25OHD) levels, reduced muscle strength and increased body mass index (BMI) are well‐known characteristics of primary hyperparathyroidism (PHPT). Mechanisms for low 25OHD levels, increased BMI and potential changes after parathyroidectomy are unknown. Muscle strength is reported to increase following surgical cure, but whether the improvement corresponds to healthy controls’ performances remains largely unknown. Patients We studied 51 patients with former PHPT [mean age 61(36–77) years] successfully treated by surgery [mean time since operation 7·4(5–15) years] and 51 sex‐ and age‐matched controls. Measurements Physical performance include “repeated chair stand” (RCS), “timed up and go” (TUG), muscle strength [hand grip, elbow flexion/extension and knee flexion/extension (60°/90°)], postural stability, biochemistry and anthropometric indices. Results Forty‐one cases had pathologically verified adenoma, three had hyperplasia and three had uncertain diagnosis whereas four had missing data. Dietary calcium intake, vitamin D supplementation and biochemistry including PTH and 25OHD levels did not differ between groups. Former patients had significantly higher BMI (28·8 ± 6·0 kg/m²) than controls (26·0 ± 4·7kg/m²). Muscle pain was more frequently reported by cases than controls, and cases performed RCS slower than controls (P = 0·02). Furthermore, female cases had lower muscle strength in knee flexion 60° (P = 0·02) and 90° (P = 0·05). Former patients no longer differed from controls after adjustment for BMI. Conclusion Following cure, 25OHD levels are normalized suggesting 25OHD insufficiency is not a constitutional characteristics in patients with PHPT. Increased BMI seems to be sustained. Whether this is caused by decreased muscle strength or reduced muscular performance causes adiposity needs further investigations.     

Efficacy of risedronate with cholecalciferol on 25-hydroxyvitamin D level and bone turnover in Korean patients with osteoporosis

Background We performed a randomized, double‐blind, prospective, 16‐week clinical trial to evaluate the efficacy and safety of risedronate with and without cholecalciferol on 25‐hydroxyvitamin D [25(OH)D] levels and bone markers in Korean patients with osteoporosis. Methods We randomly assigned 164 adults with osteoporosis to one of two treatment groups: weekly risedronate 35 mg and cholecalciferol 5600 IU combined in a single pill (RSD+) or weekly risedronate 35 mg alone (RSD). We measured serum levels of 25(OH)D, parathyroid hormone (PTH), and bone markers and performed muscle function tests, at baseline and after 16 weeks of treatment. Results After 16 weeks of treatment, mean serum 25(OH)D increased significantly from 39·8 to 70·8 nmol/l in the RSD+ group and declined significantly from 40·5 to 35 nmol/l in the RSD group. Although both treatment groups had significant increases in serum PTH over baseline during the study, the RSD group had a significantly larger increase than the RSD+ group (13·6 vs 4·8 ng/l; P = 0·0005). In both groups, serum bone‐specific alkaline phosphatase (BSAP) and C‐terminal telopeptide (CTX) declined rapidly; there were no significant differences between groups. There was also no significant difference between groups in lower‐extremity function tests. The overall incidence of clinical adverse events was not significantly different between groups. Conclusion In patients with osteoporosis, a once‐weekly pill of risedronate and cholecalciferol provided equivalent antiresorptive efficacy to risedronate alone in terms of bone turnover and improved 25(OH)D level over a 16‐week treatment period without significant adverse events.     

Serum concentrations of 17β-E2 and 25-hydroxycholecalciferol (25OHD) in relation to all-cause mortality in older men – the MINOS study

Objective To examine the association of serum hormone levels with all‐cause mortality in older community‐dwelling men. Design Single centre cohort study. Subjects Men aged 50 and older, insured by Société de Secours Minière de Bourgogne (Montceau les Mines, France). Among 3400 men invited to participate, 782 volunteers had serum hormone measurements and were followed up for 10 years. No exclusion criteria were used. Results Nonsurvivors (n = 182) were older, had more comorbidities and lower physical performance. The lowest quartile of 25‐hydroxycholecalciferol (25OHD) level predicted mortality [HR = 1·44, 95% confidence interval (CI): 1·03–2·03, P < 0·05] regardless of age, BMI, smoking, physical activity, vitamin D supplementation, and health status; mainly for the first 3 years. The 17β‐E₂ level predicted mortality independent of confounders after the third year (HR = 1·21 per 1 SD increase, 95% CI: 1·09–1·35, P < 0·001). In the fully adjusted models, risk of death increased per quartiles of 17β‐E₂ (trend –P < 0·001) and was higher in the third and the fourth quartiles compared with the lowest quartile (HR = 1·80, 95% CI: 1·09–2·98, P < 0·05 and HR = 2·83, 95% CI: 1·71–4·67, P < 0·001). Concentrations of testosterone and PTH did not predict mortality independent of the model. Conclusions In older men, increased 17β‐E₂ level predicted mortality after 3 years of follow‐up. Thus, high 17β‐E₂ level may reflect presence of risk factors precipitating development of diseases. Low 25OHD level predicted mortality more weakly, mainly for the first 3 years of the follow‐up, and was strongly influenced by the confounding variables. Thus, low 25OHD level may reflect poor current health status and unhealthy lifestyle.     

Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight

Objectives Obestatin and ghrelin, which are derived from the same gene, are observed to have opposite effects on weight status. The aims of this study were to compare obestatin concentrations in obese and normal‐weight children and to analyse the effect of weight loss on obestatin and ghrelin levels. Methods We examined anthropometrical markers and fasting serum obestatin, ghrelin, leptin, glucose and insulin concentrations in 44 obese children (mean age 11·2 years) before and after participating in a 1‐year outpatient obesity intervention programme based on a high‐carbohydrate, fat‐reduced diet and increased physical activity. Additionally, total ghrelin, obestatin and leptin levels were determined in 22 normal‐weight healthy children of similar age, gender and pubertal stage. Results Obestatin and leptin concentrations were significantly (P < 0·001) higher and ghrelin concentrations were significantly (P < 0·001) lower in obese children compared to nonobese children. In contrast to the 13 children without weight loss, substantial weight loss in 31 children led to a significant (P = 0·007) increase in obestatin and to a significant (P < 0·05) decrease in leptin and insulin concentrations, while ghrelin concentrations did not change significantly. Children with substantial weight loss demonstrated significantly (P = 0·009) lower obestatin and a tendency (P = 0·064) to higher ghrelin concentrations at baseline. Changes in insulin were not related to changes in ghrelin or obestatin. Conclusion The increase in obestatin and the decrease in ghrelin in obese children point towards an adaptation process of weight status. Weight reduction due to a long‐term lifestyle intervention resulted in an increase in obestatin levels.     

Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans

Background Obesity disproportionately affects African Americans (AA) (especially women), and is linked to depressed 25‐hydroxyvitamin D (25‐OH D) and elevated parathyroid hormone (PTH). The relationship of 25‐OH D and PTH with body composition and size in AA is not well known. Objective To determine the relationship of 25‐OH D and PTH levels with body composition and anthropometric measures. Design A cross‐sectional study was conducted in 98 healthy, overweight, adult AA enrolled in an NIH/NIEHS‐sponsored weight loss/salt‐sensitivity trial. Measurements Multivariable linear regression analyses were used to explore the relationship of 25‐OH D and PTH with body composition, determined by dual‐energy X‐ray absorptiometry, and anthropometric measures. Body composition and size were contrasted across vitamin D/PTH groups using general linear models: (i) normal (25‐OH D >50 nmol/l, PTH ≤65 pg/ml), (ii) low 25‐OH D and normal PTH and (iii) low 25‐OH D and high PTH. Results Age, gender and season‐adjusted regression analyses showed that PTH was directly correlated with total (P = 0·02), truncal (P = 0·03) and extremity (P = 0·03) fat mass, while 25‐OH D was inversely related to truncal fat mass (P = 0·02). Total fat mass in groups 1–3, respectively, was 30·0, 34·0 and 37·4 kg (P = 0·008); truncal fat mass was 13·4, 15·9 and 17·6 kg (P = 0·006) and extremity fat mass was 15·8, 16·9 and 19·7 kg (P = 0·02). Lean mass did not differ across the three groups. Conclusions Our findings show that lower 25‐OH D and raised PTH are both correlated, though in opposite directions, with fat mass, fat distribution and anthropometric measures in adult AA.     

Acylated ghrelin and leptin in adolescent athletes with amenorrhea, eumenorrheic athletes and controls: a cross-sectional study

Objectives Neuroendocrine factors may predict which athletes develop amenorrhea and which athletes remain eugonadal. Specifically, ghrelin and leptin have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that adolescent athletes with amenorrhea (AA) would have higher ghrelin and lower leptin levels than eumenorrheic athletes (EA) and would predict levels of gonadal steroids. Design Cross‐sectional Subjects and measurements We enrolled 58 girls, 21 AA, 19 EA and 18 nonathletic controls 12–18 years old. Fasting blood was drawn for active ghrelin, leptin, E₂ and testosterone. Athletes were > 85% of ideal body weight for age based on body mass index (BMI). Results AA girls had lower BMI than EA and controls (P = 0·003). Log ghrelin was higher in AA than in EA and controls (P < 0·0001), and remained higher after controlling for BMI Z‐scores. Leptin was lower in AA than in the other groups (P < 0·0001), however, the differences did not persist after controlling for BMI Z‐scores. Testosterone was lower in AA than in EA and controls (P = 0·002) and log E₂ trended lower in AA (P = 0·07). We observed inverse associations of log active ghrelin with testosterone (P = 0·01), and positive associations of leptin with testosterone and log E₂ (P = 0·02 and 0·009). Conclusion Higher ghrelin levels, even after controlling for BMI, and lower leptin in AA compared with EA and controls, and their inverse and positive associations, respectively, with gonadal steroids suggest endocrine perturbations that may explain why hypogonadism occurs in some but not all athletes.