La-or Chailurkit

Serum oestradiol and oestrogen‐receptor gene polymorphism are associated with bone mineral density independently of serum testosterone in normal males

The physiological effects of oestrogens on bone in men were largely unanticipated until recently, when oestrogen deficiency in males with aromatase deficiency and oestrogen resistance was found to cause osteoporosis and delayed fusion of epiphyses despite sufficient serum testosterone. This raises the possibility that in normal men oestrogens rather than androgens are of physiological importance in bone maturation. In the present study, we examined the association of serum oestradiol (E2) compared to that of free testosterone (FT) with bone mineral density (BMD) in normal men. The effect of oestrogen receptor (ER) gene polymorphism on BMD in men was also addressed.

Oestrogen-receptor-α gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women

An oestrogen‐receptor‐α (ERα) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERα gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post‐menopausal women in relation to ERα gene polymorphism.

Estrogen receptor gene polymorphism is associated with bone mineral density in premenopausal women but not in postmenopausal women

In the present study, we examined the genotypes distribution of Pvu II estrogen receptor (ER) gene polymorphism and its association to bone mass in Thai females. Subjects consisted of 134 Thai females 54 of whom were premenopausal and 80 were postmenopausal. Pvu II ER gene polymorphism was determined by PCR-RFLP. Capital P represents the absence of the restriction site while small p indicates the presence of the restriction site. Forty nine (36.6%) of the subjects had pp genotype, while 59 (44.0%) had Pp genotype and 26 (19.4%) had PP genotype. There was no significant difference in age, body weight, height and calcium intake in premenopausal women with different genotypes. The results including years since menopause were similar in postmenopausal women. When including ER gene genotypes, age, body weight, height and dietary calcium intake in a stepwise multiple regression model, it was found that besides body weight ER gene polymorphism was associated with bone mineral density (BMD) at AP spine (p<0.05), lateral spine (p<0.05) femoral neck (p<0.05) and femoral trochanter (p<0.05) with the pp genotype having the least BMD. ER gene polymorphism was the only factor associated with BMD at Ward’s triangle, (p<0.05) while only body weight was associated with BMD at distal and mid radius. There was no difference in serum intact osteocalcin (OC) concentrations among subjects with different genotypes. ER gene polymorphism was not related to BMD in postmenopausal women at any skeletal site. Similarly, serum intact OC levels were not different among postmenopausal women with different genotypes. We concluded that Pvu II estrogen receptor gene polymorphism is associated with bone mineral density in premenopausal women but not in postmenopausal women. Estrogen receptor gene polymorphism may have a modulatory role in calcium and bone metabolism during adolescence and young adulthood.

Regional variation and determinants of vitamin D status in sunshine-abundant Thailand

BackgroundVitamin D insufficiency is highly prevalent. Most of the studies concerning vitamin D status were generated from countries situated at temperate latitudes. It is less clear what the extent of vitamin D insufficiency is in countries situated in the tropics and how geographical regions within country would affect vitamin D status. In the present study, we investigated vitamin D status in Thais according to geographical regions and other risk factors.MethodsSubjects consisted of 2,641 adults, aged 15 - 98 years, randomly selected from the Thai 4th National Health Examination Survey (2008-9) cohort. Serum 25 hydroxyvitamin D were measured by liquid chromatography/tandem mass spectrometry. Data were expressed as mean ± SE.ResultsSubjects residing in Bangkok, the capital city of Thailand, had lower 25(OH)D levels than other parts of the country (Bangkok, central, northern, northeastern and southern regions: 64.8 ± 0.7, 79.5 ± 1.1, 81.7 ± 1.2, 82.2 ± 0.8 and 78.3 ± 1.3 nmol/L, respectively; p < 0.001). Within each region, except for the northeastern part of the country, subjects living inside municipal areas had lower circulating 25(OH)D (central, 77.0 ± 20.9 nmol/L vs 85.0 ± 22.1 nmol/L, p < 0.001; north 79.3 ± 22.1 nmol/L vs 86.8 ± 21.8 nmol/L, p < 0.001; northeast 84.1 ± 23.3 nmol/L vs 87.3 ± 20.9 nmol/L, p = 0.001; south, 76.6 ± 20.5 nmol/L vs 85.2 ± 24.7 nmol/L, p < 0.001). Overall, the prevalence of vitamin D insufficiency was 64.6%, 46.7%, and 33.5% in Bangkok, municipal areas except Bangkok, and outside municipal area in other parts of the country, respectively. In addition, the prevalence of vitamin D insufficiency according to geographical regions was 43.1%, 39.1%, 34.2% and 43.8% in the central, north, northeast and south, respectively. After controlling for covariates in multiple linear regression analysis, the results showed that low serum 25(OH)D levels were associated with being female, younger age, living in urban and Bangkok.ConclusionsVitamin D insufficiency is common and varies across geographical regions in Thailand.

A reduced serum level of total osteocalcin in men predicts the development of diabetes in a long‐term follow‐up cohort

Background  Osteocalcin (OC), an osteoblast‐specific protein, has been demonstrated to affect glucose metabolism in both animals and humans. Studies in animals have shown an effect of undercarboxylated OC (ucOC) on beta‐cell proliferation and insulin resistance. It remains unclear whether OC is associated with the future development of diabetes in humans, as well as the relative importance of ucOC vs OC.

Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D3 or D2supplementation

BackgroundIt is not known whether genetic variation in the vitamin D binding protein (DBP) influences 25-hydroxyvitamin D levels [25(OH)D] after vitamin D supplementation. We aimed to investigate the changes of total 25(OH)D, 25(OH)D3 and 25(OH)D2 in a Thai cohort, according to type of vitamin D supplement (vitamin D3 or D2) and DBP genotype, after receiving vitamin D3 or D2 for 3 months.MethodsThirty-nine healthy subjects completed the study. All subjects received 400 IU of either vitamin D3 or D2, plus a calcium supplement, every day for 3 months. Total serum 25(OH)D, 25(OH)D3 and 25(OH)D2 were measured by LC-MS/MS. Individual genotyping of rs4588 in the DBP gene was performed using real-time PCR.ResultsVitamin D3 supplementation of 400 IU/d increased 25(OH)D3 significantly (+16.2 ± 4.2 nmol/L, p <0.001). Vitamin D2 (400 IU/d) caused increased 25(OH)D2 levels (+22.0 ± 2.11 nmol/L, p <0.001), together with a decrease of 25(OH)D3 (−14.2 ± 2.0 nmol/L, p <0.001). At 3 month, subjects in vitamin D3 group tended to have higher total 25(OH)D levels than those in vitamin D2 (67.8 ± 3.9 vs. 61.0 ± 3.0 nmol/L; p = 0.08). Subjects were then classified into two subgroups: homozygous for the DBP rs4588 C allele (CC), and the rest (CA or AA). With D3 supplementation, subjects with CA or AA alleles had significantly less increase in 25(OH)D3 and total 25(OH)D when compared with those with the CC allele. However, no difference was found when the supplement was vitamin D2.ConclusionGenetic variation in DBP (rs4588 SNP) influences responsiveness to vitamin D3 but not vitamin D2.

Vitamin D receptor gene polymorphism is associated with urinary calcium excretion but not with bone mineral density in postmenopausal women

Polymorphism of vitamin D receptor (VDR) gene has been found to be associated with serum osteocalcin (OC) levels and bone mineral density (BMD) in Caucasian identical twins and unrelated postmenopausal women. Being ethnically different and living in a geographic area with adequate vitamin D status due to abundant sunshine exposure, it is unclear whether VDR gene polymorphism will affect bone mass in Thai population. In the present study, we investigated the association between VDR gene polymorphism and bone metabolism in Thai postmenopausal women. Subjects consisted of 84 postmenopausal women. Bsm I, Taq I and Apa I polymorphisms of VDR gene were determined by PCR-RFLP. B, T and A represent the absence of the corresponding restriction sites while b, t and a indicate the presence of the restriction sites. Data were expressed as mean ± SE. Sixty-six subjects (78.6%) had bb genotype while 18 (21.4%) had Bb genotype. None of the subjects was found to have BB genotype. Taq I restriction site was in linkage disequilibrium to the Bsm I site. For Apa I polymorphism, 33 (39.3%), 42 (50.0%) and 9 (10.7%) of the subjects had aa, Aa and AA genotypes, respectively. There was no significant difference in serum intact OC levels and BMD at various skeletal sites among subjects with different genotypes. Despite the lack of difference in BMD and intact OC levels, subjects with bb genotype had higher 24-hour urinary calcium excretion than those with Bb genotype (bb, 6.1 ±0.3 mmol/day; Bb, 4.4±0.6 mmol/day; p<0.05). The effect of Bsm I VDR genotype was still significant (p<0.05) after dietary calcium intake was controlled using analysis of covariance. Despite the difference in urinary calcium levels, there was no significant difference in fractional excretion of calcium among subjects with different Bsm I-related genotypes, suggesting that the effect of the VDR gene polymorphism on urinary calcium excretion is more likely due to the effect on intestinal calcium absorption rather than renal tubular calcium reabsorption. We conclude that VDR genotype distributions in Thai postmenopausal women are different from those reported in Caucasians. VDR gene polymorphism does not appear to be associated with BMD or bone turnover in Thai postmenopausal women. However, Bsm I VDR polymorphism may have physiologic role in calcium homeostatasis by modulating intestinal calcium absorption.

Serum Uric Acid Levels in Relation to Bone-Related Phenotypes in Men and Women

Serum uric acid levels have recently been found to be associated with bone mineral density (BMD) in elderly males. The purpose of the present study was to investigate the relationship between bone-related phenotypes and serum uric acid levels in young and middle-aged males and females. Subjects consisted of 1320 males and 485 females aged 25-54 yr. Bone densitometry and quantitative ultrasonometry (QUS) were performed on each subject. Serum uric acid and biochemical markers of bone turnover were measured in fasting serum samples. When adjusted for covariates including age, body weight, and serum creatinine in multiple linear regression models, it was found that there was a positive association between uric acid levels and BMD in males at the lumbar spine (p < 0.05). The association between uric acid levels and BMD was found in females after controlling for age, body weight, and serum creatinine at the femoral neck, but in the opposite direction (p < 0.05). Uric acid levels were related to the stiffness index (SI) as assessed by QUS in males, independent of age, body weight, and serum creatinine (p < 0.05). No association between uric acid and SI in females was found. The present study demonstrated a positive association in males between serum uric acid levels and BMD, and SI from QUS, suggesting a beneficial influence of uric acid on both the quantity and quality of bone in males.

High vitamin D status in younger individuals is associated with low circulating thyrotropin.

BACKGROUND Vitamin D is an immunomodulator and may affect autoimmune thyroid diseases. Vitamin D has also been shown to influence thyrocytes directly by attenuating thyrotropin (TSH)-stimulated iodide uptake and cell growth. However, it is unclear how vitamin D status is related to TSH at the population level. The goal of the present study was to investigate the relationship between vitamin D status and TSH levels according to thyroid autoantibodies in a population-based health survey in Thailand. METHODS A total of 2582 adults, aged 15-98 years, were randomly selected according to the geographical region from the Thailand 4th National Health Examination Survey sample. By study design, the sexes were equally represented. Serum levels of 25-hydroxyvitamin D [25(OH)D], TSH, the thyroid peroxidase antibody (TPOAb), and the thyroglobulin antibody (TgAb) were measured in all subjects. RESULTS The mean age was 55.0±0.4 (SE) years. In subjects positive for serum TgAb, serum TSH levels were higher, whereas total serum 25(OH)D levels were lower. In addition, the prevalence of vitamin D insufficiency in TgAb-positive subjects was significantly higher than that observed in TPOAb- and TgAb-negative subjects, whether based on cutoff values of 20 or 30 ng/mL: 8.3% vs. 5.6%, p<0.05; or 47.6% vs. 42.0%, p<0.05, respectively. However, vitamin D status was not associated with positive TPOAb and/or TgAb after controlling for sex and age. To explore the probable interaction between vitamin D status and age on serum TSH, analyses were performed according to age tertiles; it was found that higher 25(OH)D levels were independently associated with lower TSH, but only in subjects in the lowest age tertile. CONCLUSIONS This population-based study showed that high vitamin D status in younger individuals is associated with low circulating TSH.

Vitamin D status and bone health in healthy Thai elderly women

OBJECTIVE The prevalence of hypovitaminosis D varies in different countries. Therefore, the current study was designed to assess vitamin D status and bone health in elderly women in Thailand, which is situated near the equator. METHODS This cross-sectional study was performed in 446 healthy women aged 60-97 y. RESULTS Serum 25-hydroxyvitamin D (25(OH)D) was 67.6 ± 15.7 (mean ± SD) nmol/L. Daily calcium intake was 309.5 ± 147.2 mg/d. Serum 25(OH)D levels tended to decline with bone mineral density (BMD) status. Based on functional health-based reference values, plasma-intact parathyroid hormone began to rise below serum 25(OH)D level 70 nmol/L and increase significantly when serum 25(OH)D was ≤ 60 nmol/L. Thirty-two percent of elderly women had 25(OH)D insufficiency (≤ 60 nmol/L). There was no trend toward a decrease in the concentration of serum 25(OH)D with age (r = -0.078, P = 0.10) and no significant inverse relationship with plasma intact parathyroid hormone values (r = -0.079, P = 0.097). However, a positive relationship was observed between serum 25(OH)D level and femoral neck BMD (r = 0.156, P = 0.001) but not lumbar spine L(2)-L(4) BMD (r = 0.093, P = 0.050). In addition, BMD at the femoral neck but not lumbar spine of the vitamin D insufficiency group was significantly lower than that of the vitamin D sufficiency group. CONCLUSION The optimum level of serum 25(OH) value in Thai elderly women should be higher than 70 nmol/L. Vitamin D insufficiency is observed in one-third of elderly women in Bangkok.