Ethnic differences in parathyroid hormone secretion and mineral metabolism in response to oral phosphate administration

Ethnic differences in bone metabolism have been reported and it has been suggested that these may be partly due to prolonged exposure to an elevated plasma parathyroid hormone (PTH) concentration or a decreased sensitivity to PTH. We explored ethnic differences in bone and mineral metabolism by 5 days of oral phosphate (P) loading to stimulate PTH secretion. Healthy older people from UK (B), The Gambia (G) and China (C), 15 individuals from each sex and ethnic group, were studied. Blood and urine samples were collected before and 2 h after P dose on days 1, 4 and 5 and on a control day. The induced changes (%) in PTH and markers of mineral and bone metabolism after 2 h and over 5 days were examined.At baseline, PTH, 1,25(OH)₂D and bone turnover markers were higher in Gambian subjects than in British and Chinese subjects (P ≤ 0.01).2 h after P loading, ionized calcium (iCa) decreased and PTH and plasma P (P) increased in all groups (P ≤ 0.01, n.s. between groups). Urinary P to creatinine ratio (uP/Cr) increased, the increase being greater in Chinese subjects than in British and Gambian subjects on days 4 and 5 (P ≤ 0.01). By day 5, fasting iCa was decreased and P increased in British and Gambian (P ≤ 0.01) but not in Chinese subjects. Fasting PTH and uP/Cr increased in all groups. There were ethnic differences in changes in bone markers, but the relationship with changes in PTH was comparable between groups.In conclusion, ethnic differences in mineral metabolism in response to 5-day P loading were found. Chinese subjects showed a more rapid renal clearance of P than British and Gambian counterparts and there were differences between the groups in the skeletal response to P loading, but no evidence was found for resistance to the resorbing effects of PTH.     

Hip fracture type: Important role of parathyroid hormone (PTH) response to hypovitaminosis D

ObjectiveTo investigate whether clinical and laboratory characteristics, including serum 25-hydroxyvitamin D (25(OH) D), PTH and parameters of mineral and bone metabolism, differ by hip fracture (HF) type.Patients and methodsWe studied prospectively 761 consecutively admitted older patients (mean age 82.3 + 8.8(SD) years; 74.9% women) with low trauma non-pathological HF. A detailed clinical examination was performed, haematologic, renal, liver and thyroid function tests, serum 25(OH)D, PTH, calcium, phosphate, magnesium, C-reactive protein (CRP) and cardiac troponin I (cTnI) measured. In a subset of 294 patients' markers of bone formation (serum osteocalcin, OC; bone specific alkaline phosphatase, BAP) and bone resorption (urinary deoxypyridinoline, DPD/Cr; N-terminal cross-linked telopeptide of type 1 collagen, NTx/Cr; both corrected to urinary creatinine, Cr) were also measured.ResultsIn the trochanteric compared to the cervical group, females were older than males and the prevalence of Parkinson's disease, mean haemoglobin and albumin levels were lower. Incidence and degree of myocardial injury (cTnl rise) and inflammatory reaction (CRP elevation) as well as length of hospital stay, need of institutionalisation or in-hospital mortality were similar in both groups. Hypovitaminosis D (25(OH)D < 50 mmol/L) was present in 77.8% of patients with cervical and in 82.1% with trochanteric HF, elevated PTH (> 6.8 pmol/L) in 30.2% and 41.3%, respectively. The associations between 25(OH)D, PTH, and parameters of mineral metabolism and bone turnover were site-specific. In multivariate analyses, PTH (both as a continuous or categorical variable) response to hypovitaminosis D was a strong independent predictor of HF type. Coexistence of vitamin D deficiency (25(OH) D< 25 nmol/L) and elevated PTH predicts trochanteric HF while blunted PTH response predicts cervical HF (OR = 3.5; 95% CI 1.5–80; p = 0.005). PTH response and phosphate status (above or below median level) correctly discriminated HF type in 73.8% of patients with vitamin D deficiency.ConclusionsHF type is significantly associated with PTH response to hypovitaminosis D and impaired phosphate homeostasis. We detected only minor differences between two main HF types with regard to a wide range of clinical and routine laboratory variables as well as short-term outcomes.     

Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis

IntroductionBreast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice.MethodsThe effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels.ResultsIn vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)₂D₃ inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49 ± 0.08 mm² versus 1.68 ± 0.15 mm², P < 0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81 ± 0.13 mm² versus 0.52 ± 0.11 mm² in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth.ConclusionVitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.     

Vitamin D metabolites and bone mineral density: The multi-ethnic study of atherosclerosis

Previous studies demonstrate associations of low 25-hydroxyvitamin D (25(OH)D) concentrations with low bone mineral density (BMD) and fractures, motivating widespread use of vitamin D supplements for bone health. However, previous studies have been limited to predominantly White populations despite differences in the distribution and metabolism of 25(OH)D by race/ethnicity. We determined associations of serum 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH₂)D₃), and parathyroid hormone (PTH) with BMD among 1773 adult participants in the Multi-Ethnic Study of Atherosclerosis (MESA) in a staggered cross-sectional study design. Vitamin D metabolites were measured using liquid chromatography-mass spectroscopy and PTH using a 2-site immunoassay from serum collected in 2000–2002. Volumetric trabecular lumbar BMD was measured from computed tomography scans performed in 2002–2005 expressed as g/cm³. We used linear regression and graphical methods to compare associations of vitamin D metabolite and PTH concentrations with BMD as the outcomes measure among White (n = 714), Black (n = 353), Chinese (n = 249), and Hispanic (n = 457) participants. Serum 25(OH)D and 24,25(OH₂)D₃ concentrations were highest among Whites and lowest among Blacks. BMD was greatest among Black participants. Higher serum 25(OH)D was only associated with higher BMD among Whites and Chinese participants (P-for-interaction = 0.054). Comparing the lowest category of 25(OH)D (< 20 ng/ml) to the highest (≥ 30 ng/ml), the adjusted mean difference in BMD was –8.1 g/cm³ (95% CI − 14.8, − 1.4) for Whites; − 10.2 g/cm³ (− 20.4, 0.0) for Chinese vs. 8.8 g/cm³ (− 2.8, 20.5) for Black and − 1.1 g/cm³ (− 8.3, 6.2) for Hispanic. Similar results were observed for serum 24,25(OH₂)D_3. Serum PTH was not associated with BMD. In a multi-ethnic population, associations of 25(OH)D with BMD were strongest among White and Chinese participants and null among Black and Hispanic participants. Further studies are needed to determine optimal biomarkers for bone health for multiple ethnic groups.     

High prevalence of vitamin D deficiency among middle-aged and elderly individuals in northwestern China: Its relationship to osteoporosis and lifestyle factors

PurposeVitamin D deficiency has reached epidemic proportions; this deficiency has been associated with osteoporosis and certain lifestyle factors in adults. This relationship is not well documented among the Lanzhou population in northwest China. This study sought to determine the prevalence of vitamin D deficiency and its risk factors in addition to its relationship with osteoporosis in a Chinese population living in Lanzhou.MethodsThis cross-sectional study involved 2942 men and 7158 women aged 40–75 years who were randomly selected from 3 communities in the Lanzhou urban district and examined medically. Levels of 25-hydroxy-vitamin D [25(OH)D] and other parameters were measured according to detailed inclusion criteria. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. Calcaneus bone mineral density (BMD) was measured by quantitative ultrasound (QUS).ResultsThe prevalence of vitamin D deficiency (25(OH)D levels < 20 ng/mL) was present in 75.2% of the entire study population. Vitamin D deficiency was more prevalent in women (79.7%) than in men (64%; P < 0.001). Multiple logistic regression analysis revealed that the significant predictors of vitamin D deficiency included coronary heart disease (CHD), obesity, dyslipidemia, older age, female sex, and smoking (all P < 0.05), whereas tea intake, moderate physical activity, milk intake, vitamin D supplementation and sun exposure were protective (all P < 0.05). No significant difference in calcaneus BMD measured by QUS was noted between subjects with < 20 ng/mL and ≥ 20 ng/mL vitamin D levels (0.53 ± 0.13 vs. 0.54 ± 0.13; P = 0.089). The risk of having osteoporosis did not increase when vitamin D levels decreased from ≥ 20 ng/mL to < 20 ng/mL after multiple adjustments (OR = 1.00; 95% CI 0.85–1.16; P = 0.357).ConclusionsVitamin D deficiency is prevalent in the middle-aged and elderly northwestern Chinese population and is largely attributed to CHD, obesity, dyslipidemia, older age, female sex, and smoking. Reduced 25(OH)D levels are not associated with an increased osteoporosis risk.     

On the combined effects of normobaric hypoxia and bed rest upon bone and mineral metabolism: Results from the PlanHab study

Bone losses are common as a consequence of unloading and also in patients with chronic obstructive pulmonary disease (COPD). Although hypoxia has been implicated as an important factor to drive bone loss, its interaction with unloading remains unresolved. The objective therefore was to assess whether human bone loss caused by unloading could be aggravated by chronic hypoxia.In a cross-over designed study, 14 healthy young men underwent 21-day interventions of bed rest in normoxia (NBR), bed rest in hypoxia (HBR), and hypoxic ambulatory confinement (HAmb). Hypoxic conditions were equivalent to 4000 m altitude. Bone metabolism (NTX, P1NP, sclerostin, DKK1) and phospho-calcic homeostasis (calcium and phosphate serum levels and urinary excretion, PTH) were assessed from regular blood samples and 24-hour urine collections, and tibia and femur bone mineral content was assessed by peripheral quantitative computed tomography (pQCT).Urinary NTX excretion increased (P < 0.001) to a similar extent in NBR and HBR (P = 0.69) and P1NP serum levels decreased (P = 0.0035) with likewise no difference between NBR and HBR (P = 0.88). Serum total calcium was increased during bed rest by 0.059 (day D05, SE 0.05 mM) to 0.091 mM (day D21, P < 0.001), with no additional effect by hypoxia during bed rest (P = 0.199). HAmb led, at least temporally, to increased total serum calcium, to reduced serum phosphate, and to reduced phosphate and calcium excretion.In conclusion, hypoxia did not aggravate bed rest-induced bone resorption, but led to changes in phospho-calcic homeostasis likely caused by hyperventilation. Whether hyperventilation could have mitigated the effects of hypoxia in this study remains to be established.     

Resistance to thyroid hormone due to mutations in the THRB gene impairs bone mass and affects calcium and phosphorus homeostasis

ContextResistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone, which is usually due to mutations in the thyroid hormone receptor β gene (THRB). Few studies have been conducted to investigate bone and mineral metabolism in RTH.ObjectiveThe objective of the study was to evaluate the clinical and biochemical parameters related to bone and mineral metabolism in RTH due to mutations in the THRB gene (RTHβ).Design and participantsWe conducted a cross-sectional study on 14 patients with RTHβ (RTHG), eight adults and six children, and 24 control subjects (CG).OutcomesSerum measures included total calcium (TCa), inorganic phosphate (iP), alkaline phosphatase (AP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), osteocalcin (OC), carboxyterminal telopeptide (CTX), and fibroblast growth factor 23 (FGF-23). We estimated the renal threshold phosphate concentration (TmPO₄/GFR) and assessed bone mass using dual X-ray absorptiometry.ResultsAdults and children with RTH showed higher serum levels of TCa than controls (P = .029 and, P = .018 respectively). However, only children with RTH exhibited lower serum levels of iP than controls (P = .048). FGF-23 was higher in RTHβ children (P = .04). RTHβ adults had lower whole-body (P = .01) and lumbar spine (P = .01) bone mineral density than control subjects. The same pattern was observed when the results were expressed as Z-scores between groups, with a lower value in RTHG than in CG for the lumbar spine of adults (P = .03). No difference was observed between groups in PTH, 25OHD, AP, OC, and CTX.ConclusionBiochemical abnormalities are seen in children with RTH (Low iP, high FGF23), while high calcium (with normal UCa) is seen in RTH subjects of all ages, and later on, in adult life, low BMD is seen. Considering that the TRα1 isoform is the predominant TR in the skeleton, we hypothesize that probably these patients may exhibit enhanced calcium flux from bone to circulation. Our data represent a challenge for new studies to unveil the control of calcium and phosphorus homeostasis and fracture risk in these patients.     

Strong relationship between vitamin D status and bone mineral density in anorexia nervosa

BackgroundAnorexia nervosa (AN) is associated with impaired bone health and low bone mineral density (BMD) as a consequence of an inadequate peak bone mass in adolescence and bone loss in young adulthood. The vitamin D status with its implications for bone health in patients affected by AN has only been examined previously in small studies.ObjectiveTo evaluate the prevalence of vitamin D deficiency and test the hypothesis that patients with AN and vitamin D deficiency might have worse bone metabolism and lower bone density as compared with AN with adequate vitamin D repletion.DesignWe analysed the vitamin D status and bone metabolism in a large cohort (n = 89) of untreated patients affected by AN, with amenorrhoea.ResultsVitamin D deficiency is widespread in untreated patients with AN: 16.9% had 25OH vitamin D levels below 12 ng/ml, 36% below 20 ng/ml and 58.4% below 30 ng/ml. PTH values were higher and BMD at both femoral sites were lower in patients with vitamin D < 20 ng/ml. Progressively higher values of BMD were observed by 4 ranks of 25 OH vitamin D values (severe deficiency: < 12 ng/ml, deficiency: ≥ 12 ng/ml and < 20 ng/ml, insufficiency: ≥ 20 and < 30 ng/ml and normal: ≥ 30 ng/ml). In patients with severe vitamin D deficiency BMD at the hip were significantly lower than that measured in groups with values over 20 ng/ml (p < 0.001 for trend). The level of significance did not change for values adjusted for BMI or body weight.ConclusionWe found a strong relationship between vitamin D status and hip BMD values with additional benefits for those with 25OHD levels above 20 ng/ml. Our results support the design of a randomized placebo-controlled clinical trial on the effect of vitamin D on BMD in patients with AN. The second point, whether 25OHD should be above 20 or 30 ng/ml remains a discussion point.     

Impact of demographic,environmental, and lifestyle factors on vitamin D sufficiency in 9084 Japanese adults

BackgroundLittle is known about correlates of vitamin D status in Asian populations. In this study, we established the prevalence of vitamin D sufficiency in the Murakami region (latitude N38°13′) in Niigata, Japan, and examined demographic, environmental, and lifestyle factors that might be associated with vitamin D sufficiency, with the aim of clarifying the relative contributions of previously described determinants of vitamin D status as well as identifying new determinants in this Japanese population.MethodsThis study involved a cross-sectional analysis of baseline data obtained from a cohort study conducted in 2011–2013. Participants were 9084 individuals aged between 40 and 74 years who provided blood samples for the determination of plasma 25-hydroxyvitamin D [25(OH)D] concentrations. Lifestyle information was obtained from 8498 participants, with some missing values regarding different lifestyle factors. Multiple logistic regression analysis was used to obtain odds ratios for vitamin D sufficiency, which was defined as a plasma 25(OH)D concentration ≥ 75 nmol/L.ResultsThe prevalence of vitamin D sufficiency (i.e., plasma 25(OH)D concentration ≥ 75 nmol/L) was 9.1%, and significant associations were observed with male gender (P < 0.0001; OR = 2.37, 95% CI: 1.84–3.05), older age (P for trend < 0.0001), lower BMI (P for trend < 0.0001), higher METs score (P for trend = 0.0138), higher vitamin D intake (P for trend = 0.0467), summer season (P for trend < 0.0001), longer duration outdoors (P for trend = 0.0026), no sunscreen use (P = 0.0135; OR = 1.40, 95% CI: 1.07–1.82), higher salmon consumption (P for trend < 0.0001), higher alcohol consumption (P for trend < 0.0001), and lower coffee consumption (P for trend = 0.0025). Unlike other populations previously reported, vitamin D sufficiency was associated with older age.ConclusionsThe prevalence of vitamin D sufficiency (i.e., 25[OH]D ≥ 75 nmol/L) was low (9.1%) in this Japanese population. A number of demographic, environmental, and lifestyle factors are associated with vitamin D sufficiency, and thus lifestyle modification may present an opportunity to achieve vitamin D sufficiency.     

Circulating concentrations of vitamin E isomers: Association with bone turnover and arterial stiffness in post-menopausal women

The effects of vitamin E on cardiovascular and bone health are conflicting with beneficial and detrimental findings reported. To investigate this further, we carried out a cross-sectional study to determine the relationship between circulating concentrations of the 2 vitamin E isomers, α- and γ-tocopherol (TP) with bone turnover and arterial stiffness.Two hundred and seventy eight post-menopausal women with mean age [SD] 60.9 [6.0] years were studied. Fasting serum α-TP and γ-TP, bone turnover markers; procollagen type 1 amino-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX), parathyroid hormone (PTH), total cholesterol (TC) and triglycerides (TG) were measured. Pulse wave velocity (PWV) and central augmentation index (AI) as markers of arterial stiffness were also determined.A positive correlation was observed between α-TP and γ-TP (r = 0.14, p = 0.022). A significant negative association between α-TP and P1NP only was seen in multiple linear regression analysis following adjustment for serum TC and TG (p = 0.016). In a full multi-linear regression model, following correction for age, years since menopause, smoking habits, alcohol intake, use of calcium supplements, BMI, PTH, serum calcium, and estimated glomerular filtration rate (eGFR), the association between α-TP and P1NP remained significant (p = 0.011). We did not observe any significant association between γ-TP or α-TP/γ-TP ratio with P1NP or CTX. P1NP was significantly lower in subjects with α-TP concentrations of > 30 μmol/L (α-TP > 30 μmol/L; P1NP: 57.5 [20.7], α-TP < 30 μmol/L; P1NP: 65.7 [24.9] μg/L, p = 0.005). PWV was significantly associated with α-TP/γ-TP ratio (p = 0.04) but not with serum α-TP or γ-TP in a full multi-linear regression model adjusting for serum lipids, age, and blood pressure. The data suggest that high serum concentrations of α-TP may have a negative effect on bone formation. The balance of α-TP and γ-TP may be important in maintaining arterial compliance. Longitudinal studies are needed to investigate the impact of the vitamin E isomers on bone and cardiovascular health.     

Seasonal changes in serum calcium,PTH and vitamin D levels in patients with primary hyperparathyroidism

BackgroundSeasonal variations of 25-hydroxyvitamin D, PTH and calcium levels are not well characterized in primary hyperparathyroidism (PHPT). Our objectives were to characterize seasonal changes in these parameters in PHPT patients, and to assess whether these seasonal changes affect clinical decision making.MethodsThis is a retrospective study based on the electronic medical records of Clalit Health service in the south of Israel between 2000 and 2012. Patients 18 years and older with PHPT (PTH > upper limit of norm (ULN) and serum calcium > 10.5 mg%) were included. Patients with renal failure or on Thiazide diuretics were excluded. All serum levels of calcium, PTH and 25-hydroxyvitamin D were collected and then stratified according to season.Results792 patients were classified as PHPT (72.2% female) and had a total of 2659 PTH tests, 1395 25-hydroxyvitamin D tests and 7426 calcium test. Fifty six percent of 25-hydroxyvitamin D levels were < 50 nmol/L. Seasonality was demonstrated in all three parameters: mean 25-hydroxyvitamin D was 13% higher in the summer compared to the winter (P < 0.001), median PTH values showed opposite trend with a fall of about 8.4% in summer compared to winter (P < 0.001). Calcium levels were higher during the autumn with a rise of about 0.2 mg/dL in the mean calcium levels compared to spring and summer (P < 0.001). The odds ratio of calcium level above 11.5 mg/dL is highest in the autumn (OR = 1.275, P = 0.018).ConclusionWe show seasonal variation in serum 25-hydroxyvitamin D, PTH, and calcium levels in patients with PHPT. These seasonal variations cause transition to pathological values that may influence diagnosis and treatment of PHPT patients.     

Third metacarpal condylar fatigue fractures in equine athletes occur within previously modelled subchondral bone

Bone modelling and remodelling reduce the risk of fatigue fractures; the former by adapting bone to its loading circumstances, the latter by replacing fatigued bone. Remodelling transiently increases porosity because of the normal delay in onset of the formation phase of the remodelling sequence. Protracted intense loading suppresses remodelling leaving modelling as the only means of maintaining bone strength. We therefore hypothesized that race horses with fatigue fractures of the distal third metacarpal bone (MC3) will have reduced porosity associated with suppressed remodelling while continued adaptive modelling will result in higher volume fraction (BV/TV) at this site. Using high resolution peripheral quantitative computed tomography (HR-pQCT), we measured the distal aspect of the MC3 obtained at postmortem from 13 thoroughbred race horses with condylar fractures of the MC3 (cases), 8 horses without fractures (training controls), 14 horses with a fracture at another site (fractured controls) and 9 horses resting from training (resting controls).Porosity of the subchondral bone of MC3 was lower in cases than resting controls (12 ± 1.4% vs. 18 ± 1.6%, P = 0.017) although areas of focal porosity were observed adjacent to fractures in 6/13 horses. BV/TV of the distal metacarpal epiphysis tended to be higher in horses with condylar fractures (0.79 ± 0.015) than training controls (0.74 ± 0.019, P = 0.070), but also higher in controls with a fracture elsewhere (0.79 ± 0.014) than the training controls (0.74 ± 0.019, P = 0.040). BV/TV was higher in horses over three years of age than those aged two or three years (0.79 ± 0.01 vs. 0.74 ± 0.01, P = 0.016). All metacarpal condylar fractures occurred within focal areas of high BV/TV.We infer that intense training in equine athletes suppresses remodelling of third metacarpal subchondral bone limiting damage repair while modelling increases regional bone volume in an attempt to minimise local stresses but may fail to offset bone fragility.     

The effect of vitamin C intake on the risk of hyperuricemia and serum uric acid level in Korean Multi-Rural Communities Cohort

ObjectiveThe aim of this study was to determine the association between vitamin C intake and risk of hyperuricemia or serum uric acid levels in male and female subjects in the Korean Multi-Rural Communities Prospective Cohort.MethodsThis cross-sectional analysis was conducted in 9400 subjects enrolled in the Korean Multi-Rural Communities Cohort Study. The risk of hyperuricemia was assessed in five quintiles (Q1 to Q5) according to dietary and total vitamin C intake using multivariate-adjusted logistic regression models. Relationships between serum uric acid levels and vitamin C intake were evaluated using linear regression analysis after adjustment for covariates. Information about dietary components was collected using validated food frequency questionnaires.ResultsDietary vitamin C intake, but not total vitamin C intake, was significantly different between hyperuricemic and non-hyperuricemic subjects in males (P = 0.01) and females (P = 0.02). The risk of hyperuricemia decreased with increased dietary vitamin C intake in male and female subjects after multivariate adjustment (P for trend = 0.002 in males and P for trend = 0.02 in females). An effect of total vitamin C intake on hyperuricemia risk was identified in females (P for trend = 0.04), but not males (P for trend = 0.06). Serum uric acid level was linearly associated with total vitamin C intake in females (β = −0.0001, P = 0.01), but not with dietary vitamin C intake in either gender.ConclusionThis study showed that vitamin C intake might be in part responsible for hyperuricemia or serum uric acid level in the Korean Multi-Rural Communities Cohort.     

Vitamin D status and common risk factors for bone fragility as determinants of quantitative ultrasound variables in a nationally representative population sample

Calcaneal quantitative ultrasound (QUS) can predict bone strength and fracture risk. Bone fragility has no single cause but results from a complex interplay of several etiologic or contributing factors. Vitamin D is essential for bone health even though it is still unclear how much of this vitamin is required to maintain bone strength and prevent fractures. Measurements of serum 25-hydroxyvitamin D [S-25(OH)D] have indicated a high prevalence of inadequate vitamin D status in a number of studies mostly based on selected study populations. The objective of this study was to examine the associations between S-25(OH)D, common risk factors for bone fragility, and QUS variables in a large unselected population sample.The study population consisted of 2736 men and 3299 women from a nationally representative population sample, aged 30 years or over. Information on lifestyle was elicited by means of interviews and questionnaires. Body fat mass was estimated using an impedance-meter. S-25(OH)D was measured by radioimmunoassay. Calcaneal QUS was performed on the Hologic Sahara apparatus recording broadband ultrasound attenuation (BUA) and speed of sound (SOS). The potential determinants of BUA and SOS were analysed using separate multiple linear regression models for men and women.S-25(OH)D proved to be an independent determinant of BUA (P < 0.0001 for men, P < 0.001 for women) and SOS (P < 0.0001 for men, P < 0.05 for women). BUA was also independently associated with age, height, weight, alcohol consumption, and postmenopausal status in women, and with weight, alcohol consumption, smoking and physical activity in men. All of the above variables, except for weight in women, were also found to be independent determinants of SOS in both men and women. A reverse association was found between S-25(OH)D and adiposity in spite of higher intakes of vitamin D in those with higher fat mass.In this unselected sample of men and women, vitamin D status, several lifestyle factors and physical characteristics proved to be significant determinants of BUA and SOS. Inadequate vitamin D status was common, and measures ensuring adequate intakes of vitamin D in the population thus deserve continued attention. Obesity should be taken into account in future assessments of vitamin D status in Finland as in other countries.     

Increased density and periosteal expansion of the tibia in young adult men following short-term arduous training

PurposeFew human studies have reported early structural adaptations of bone to weight-bearing exercise, which provide a greater contribution to improved bone strength than increased density. This prospective study examined site- and regional-specific adaptations of the tibia during arduous training in a cohort of male military (infantry) recruits to better understand how bone responds in vivo to mechanical loading.MethodsTibial bone density and geometry were measured in 90 British Army male recruits (ages 21 ± 3 years, height: 1.78 ± 0.06 m, body mass: 73.9 ± 9.8 kg) in weeks 1 (Baseline) and 10 of initial military training. Scans were performed at the 4%, 14%, 38% and 66% sites, measured from the distal end plate, using pQCT (XCT2000L, Stratec Pforzheim, Germany). Customised software (BAMPack, L-3 ATI) was used to examine whole bone cross-section and regional sectors. T-tests determined significant differences between time points (P < 0.05).ResultsBone density of trabecular and cortical compartments increased significantly at all measured sites. Bone geometry (cortical area and thickness) and bone strength (i, MM_i and BSI) at the diaphyseal sites (38 and 66%) were also significantly higher in week 10. Regional changes in density and geometry were largely observed in the anterior, medial–anterior and anterior–posterior sectors. Calf muscle density and area (66% site) increased significantly at week 10 (P < 0.01).ConclusionsIn vivo mechanical loading improves bone strength of the human tibia by increased density and periosteal expansion, which varies by site and region of the bone. These changes may occur in response to the nature and distribution of forces originating from bending, torsional and shear stresses of military training. These improvements are observed early in training when the osteogenic stimulus is sufficient, which may be close to the fracture threshold in some individuals.     

Association of vitamin D receptor gene TaqI,BsmI, FokI and ApaI polymorphisms and susceptibility to extremity chronic osteomyelitis in Chinese population

Previous studies have indicated that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with the risk of several inflammatory diseases. However, potential association of the VDR gene polymorphisms with susceptibility to extremity chronic osteomyelitis remains unclear. The present study aimed to investigate link between VDR gene polymorphisms and the risk of extremity chronic osteomyelitis in Chinese population. A total of 233 patients with chronic osteomyelitis and 200 healthy controls were genotyped for the 4 single-nucleotide polymorphisms (SNPs) (TaqI, BsmI, FokI and ApaI) in VDR gene using the SNaPshot genotyping method. The frequencies of mutant allele C in rs731236 (P = 0.044, OR = 1.830, 95% CI 1.009 − 3.319) and rs2228570 (P = 0.029, OR = 1.347, 95% CI 1.031 − 1.761) were significantly higher in patients than those in healthy controls. In addition, outcomes of the logistic regression analysis adjusted by gender and age revealed that significant links were found between rs731236 (P = 0.05, OR = 1.887, 95% CI 1.001 − 3.558), rs2228570 (P = 0.042, OR = 1.594, 95% CI 1.016–2.500) and the risk of developing chronic osteomyelitis by dominant genetic model. In addition, significant association was also found between rs2228570 and the risk of developing the disease by homozygous model (P = 0.034, OR = 1.803, 95% CI 1.046 − 3.106). However, no significant correlations were found between BsmI (rs1544410) or ApaI (rs7975232) gene polymorphisms and the susceptibility to the disease. To our knowledge, we reported for the first time that VDR gene TaqI (rs731236) and FokI (rs2228570) polymorphisms may contribute to the increased risk of chronic osteomyelitis in Chinese population.     

Tibial bone responses to 6-month calcium and vitamin D supplementation in young male jockeys: A randomised controlled trial

Young male jockeys compromise bone health by engaging in caloric restriction and high volumes of physical activity during periods of musculoskeletal growth and development. The aim of this randomised, double-blinded, placebo-controlled trial was to establish whether calcium and vitamin D supplementation would improve bone properties of young male jockeys. We conducted a 6-month trial with two groups of weight-, height- and age-matched apprentice male jockeys (age = 20.2 ± 3.2 yrs). Participants were supplemented with 800 mg of calcium and 400 IU of vitamin D (S, n = 8) or a placebo (cellulose) (P, n = 9) daily for 6-months. Baseline calcium intake was (669.7 ± 274.3 (S) vs 790.4 ± 423.9 (P) and vitamin D 64.6 ± 19.5 (S) vs 81.2 ± 24.4 (P) with no statistical differences. Peripheral quantitative computed tomography (pQCT) measured ultra-distal (4%) and proximal (66%) tibial bone properties at baseline and 6 months. Blood-borne markers of bone turnover, P1NP and CTX and vitamin D concentration were assessed. After co-varying for height, weight and baseline bone measurements, the supplemented group displayed greater post-intervention bone properties at the 66% proximal site with cortical content (mg mm) 6.6% greater (p < 0.001), cortical area (mm²) 5.9% larger (p < 0.001), cortical density (mg cm²) 1.3% greater (p = 0.001), and total area (mm²) 4% larger (p = 0.003). No other between group differences in bone variables were observed. Blood analysis indicated higher vitamin D levels (18.1%, p = 0.014) and lower CTx (ng/L) (− 24.8%, p = 0.011) in the supplemented group with no differences observed in P1NP. This is the first randomised controlled trial to examine the efficacy of calcium and vitamin D supplementation in improving bone properties in a highly vulnerable, young athletic, weight-restricted population. Results using pQCT indicate beneficial effects of supplementation on bone properties in as little as six months. Although the study size is small, this intervention appears promising as a strategy for improving bone health in young athletes in weight-restricted sports.     

The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma

Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis.We examined 93 patients with DTC over 12 months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1 year.The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12 months, were − 0.88, − 1.3 and − 0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine − 2.1%, femoral neck − 2.2%, and hip − 2.1%; all P < 0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P = 0.041) and femoral neck (P = 0.010).TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period.     

Different osteocalcin forms,markers of metabolic syndrome and anthropometric measures in children within the IDEFICS cohort

ObjectiveOsteocalcin (OC), an aboundant non-collagenous bone protein, is inversely associated with parameters of glucose metabolism. Interactions between bone tissue and energy metabolism have not been thoroughly investigated during childhood. This study investigated OC, metabolic parameters and anthropometric characteristics in normal weight and overweight/obese children.MethodsThis study comprised 108 (46 normal weight/62 overweight/obese) Swedish 2–9 year old children. Anthropometric data, insulin, glucose, glycosylated haemoglobin (HbA1c), HOMA index, vitamin D, adiponectin, total OC, carboxylated OC (cOC) and undercarboxylated OC (ucOC) were analysed.ResultsNo difference was found for total OC between the normal and overweight/obese groups, with a mean (± SD) value of 82.6 (± 2.8) ng/mL and 77.0 (± 2.4) ng/mL, (P = 0.11), respectively. Overweight children had lower cOC levels, mean 69.1 (± 2.2) ng/mL, vs. normal weight children, mean 75.6 (± 2.5) ng/mL (P = 0.03). The mean ucOC levels of 7.9 (± 0.4) ng/mL in overweight children did not differ vs. normal weight children, mean level 7.0 (± 0.4) ng/mL, (P = 0.067). None of the three OC forms correlated with any of the measured parameters.ConclusionsThe cOC levels were lower in overweight children. There was no correlation between the three OC forms and any of the measured anthropometric or metabolic parameters. OC has been suggested to have a possible metabolic role, but in general the current study in prepubertal children does not support the hypothesis of an association between OC and a positive metabolic profile.