Serum C3 epimer of 25-hydroxyvitamin D and its determinants in adults: a national health examination survey in Thais.

UNLABELLED: A high percentage have detectable C3 epimer of 25-hydroxyvitamin D3 (3-epi-25(OH)D3) in the population of Thai National Health Examination Survey IV. INTRODUCTION: C3 epimers of vitamin D have recently been shown to contribute significantly to 25-hydroxyvitamin D (25(OH)D) levels in an infant population. However, the findings in the general adult population are unclear. Therefore, the purpose of the present study is to determine the percentage of the C3 epimer of 25(OH)D (3-epi-25(OH)D) and its determinants in an adult population. METHODS: A subsample of 1148 sera randomly selected from the Thai National Health Examination Survey IV (2009) samples were measured for serum 25(OH)D2, 25(OH)D3, 3-epi-25(OH)D2, and 3-epi-25(OH)D3 by LC-MS/MS method. The relative 3-epimer contribution (%) was used to express the amount of 3-epimer-25(OH)D3 as a percentage of total 25(OH)D3 (the sum of 25(OH)D3, and 3-epi-25(OH)D3). RESULTS: A high proportion of subjects had detectable 3-epi-25(OH)D3 that was <10 % of the total 25(OH)D levels. Since the level of total 25(OH)D2 is low, only a minority of subjects had detectable 3-epi-25(OH)D2. Multivariate analysis suggested that age, male gender, and rural residence were independently related to the 3-epi-25(OH)D3/total 25(OH)D3 ratio. CONCLUSIONS: A high percentage of Thai adults had detectable 3-epi-25(OH)D3 that was <10 % of the total 25(OH)D levels. Age, gender, and living in a rural area were associated with the relative amount of 3-epi-25(OH)D3 to total 25(OH)D3.

Causal relationship between the AHSG gene and BMD through fetuin-A and BMI: multiple mediation analysis.

UNLABELLED: Using mediation analysis, a causal relationship between the AHSG gene and bone mineral density (BMD) through fetuin-A and body mass index (BMI) mediators was suggested. INTRODUCTION: Fetuin-A, a multifunctional protein of hepatic origin, is associated with bone mineral density. It is unclear if this association is causal. This study aimed at clarification of this issue. METHODS: A cross-sectional study was conducted among 1,741 healthy workers from the Electricity Generating Authority of Thailand (EGAT) cohort. The alpha-2-Heremans-Schmid glycoprotein (AHSG) rs2248690 gene was genotyped. Three mediation models were constructed using seemingly unrelated regression analysis. First, the ln[fetuin-A] group was regressed on the AHSG gene. Second, the BMI group was regressed on the AHSG gene and the ln[fetuin-A] group. Finally, the BMD model was constructed by fitting BMD on two mediators (ln[fetuin-A] and BMI) and the independent AHSG variable. All three analyses were adjusted for confounders. RESULTS: The prevalence of the minor T allele for the AHSG locus was 15.2%. The AHSG locus was highly related to serum fetuin-A levels (P < 0.001). Multiple mediation analyses showed that AHSG was significantly associated with BMD through the ln[fetuin-A] and BMI pathway, with beta coefficients of 0.0060 (95% CI 0.0038, 0.0083) and 0.0030 (95% CI 0.0020, 0.0045) at the total hip and lumbar spine, respectively. About 27.3 and 26.0% of total genetic effects on hip and spine BMD, respectively, were explained by the mediation effects of fetuin-A and BMI. CONCLUSIONS: Our study suggested evidence of a causal relationship between the AHSG gene and BMD through fetuin-A and BMI mediators.

The efficacy of calcium supplementation alone in elderly Thai women over a 2-year period: a randomized controlled trial.

UNLABELLED: Supplementation with elemental calcium 500 mg/day alone for 2 years is able to decrease bone turnover and is effective in retarding bone loss at lumbar spine and slowing bone loss at femoral neck in elderly Thai women who had low dietary calcium intake. INTRODUCTION: Most elderly Thais have a total dietary calcium intake of less than the recommended amount. The aim of the study was to investigate the effect of calcium supplementation on bone mineral density and biochemical indices of bone remodeling in Thai postmenopausal women. METHODS: Four hundred and four healthy postmenopausal women 60 years old or older without osteoporosis were recruited and conducted in a randomized, double-blinded, placebo-controlled trial. They were randomly given elementary calcium 500 mg/day or placebo for 2 years. Dietary calcium intake was calculated from the nutrient compositional analysis of the 3-day food records. Serum 25 hydroxyvitamin D was measured by radioimmunoassay and bone turnover markers were determined by electrochemiluminescence immunoassay. RESULTS: The age of the subjects was 65.8 ± 4.4 years. All baseline characteristics of the subjects in the calcium-supplemented group and the placebo group were not statistically different. At the end of the study, significant decreases in serum C-terminal telopeptide of type I collagen and serum total procollagen type I amino terminal propeptide in the calcium-supplemented group were observed, while there was no change in the placebo group. In addition, plasma parathyroid hormone decreased, although not significantly, only in the calcium-supplemented group. Percent changes from baseline of lumbar spine (L2-L4) bone mineral density increased 2.76% in the calcium-supplemented group and 0.87% in the placebo group, whereas the percent changes from baseline of femoral neck decreased 0.21% in the calcium-supplemented group and 0.90% in the placebo group. CONCLUSIONS: Calcium supplementation is necessary for the decrease of bone turnover and prevention of bone loss in Thai elderly women.

Malic enzyme gene polymorphism is associated with responsiveness in circulating parathyroid hormone after long-term calcium supplementation.

OBJECTIVE: To identify genetic variations associated with parathyroid hormone (PTH) suppression after long-term calcium supplementation. DESIGN AND PARTICIPANTS: For high throughput SNP screening, subjects consisted of 171 postmenopausal women without osteoporosis at the lumbar spine. A separate group of 19 premenpausal women were recruited for calcium absorption study. Postmenopausal women in the screening group were given 500 mg/day calcium supplementation. SETTING: Bangkok, Thailand. MEASUREMENTS: Parathyroid hormone (PTH) and bone mineral density (BMD) were measured at baseline and 2 years after calcium supplementation. High throughput single-nucleotide polymorphism (SNP) screening was performed by comparing estimated allele frequencies derived from hybridization signal intensities of pooled DNA samples on Affymetrix's 10K SNP genotyping microarrays based responsiveness in PTH after calcium supplementation. Genotyping of SNP rs1112482 in malic enzyme gene (ME1) gene, a SNP among those with highest odds ratio of being related to PTH suppression after calcium, was performed in all postmenopausal subjects in the screening group and premenopausal women in the calcium absorption study group in which fractional calcium absorption was assessed by stable isotope dilution. Data were expressed as mean +/- SEM. RESULTS: PTH significantly decreased after 2 years of calcium supplementation (4.7 ± 1.9 vs. 4.4 ± 1.6 pmol/L, P < 0.01). There was a significant increase in lumbar spine BMD (1.03 ± 0.01 vs. 1.01 ± 0.01 g/cm2, P < 0.001) but not femoral neck BMD. In 108 subjects whose PTH levels decreased after calcium, the suppression of PTH was higher in those with at least one C allele in rs1112482 of ME1 gene (-26.3 ± 2.1 vs. -16.9 ± 1.4%, P < 0.001). Fractional calcium absorption also tends to the higher in subjects in the calcium absorption study group with at least one C allele (n = 6) compared to those without the C allele (n = 13) (58.0 ± 4.9 vs. 49.3 ± 2.8%, P = 0.054). CONCLUSION: Cytosolic malic enzyme 1 gene polymorphism is associated with the degree of suppression of parathyroid hormone after long-term calcium supplementation. The effect is probably mediated through an increase in intestinal calcium absorption.

Vitamin D status and glucose homeostasis in obese children and adolescents living in the tropics.

BACKGROUND: Pediatric obesity continues to rise and has become a major health problem worldwide. Vitamin D deficiency has been increasing among obese non-Asian children and is associated with abnormal glucose homeostasis in obese adults. However, data on the vitamin D status and its association with glucose homeostasis in obese children residing in tropical Asian countries are unavailable. OBJECTIVE: To assess vitamin D status and glucose homeostasis in obese Thai children. PATIENTS AND METHODS: A total of 150 obese, and 29 healthy non-obese children and adolescents were enrolled. Weight, height, body mass index (BMI) and waist circumference were obtained. All obese children underwent an oral glucose tolerance test with glucose and insulin measurements. Plasma 25-hydroxyvitamin D (25-OHD) and calciotropic blood chemistries were measured in all participants. Insulin sensitivity indices were calculated from the measured glucose and insulin levels. RESULTS: Approximately 25% of the obese children and adolescents had impaired glucose tolerance, impaired fasting plasma glucose (FPG) and diabetes. Seventeen out of 150 (11.3%) obese children and 3 out of 29 (10.3%) non-obese children had vitamin D deficiency, which was defined as a 25-OHD level of <50 nmol l(-1). Glucose tolerance and insulin sensitivity indices were comparable between obese children with sufficient vitamin D and those with vitamin D deficiency. There were no relationships among serum 25-OHD; weight, height, and BMI standard deviation scores; insulin sensitivity indices; FPG and insulin; and 2-h plasma glucose and insulin levels. CONCLUSION: Vitamin D deficiency is not as prevalent in obese Thai children as in obese non-Asian children from high-latitude countries. Adiposity per se is unlikely to be a determinant of vitamin D status in these obese individuals. There was no association between vitamin D deficiency and abnormal glucose homeostasis.

Hypertension is statistically associated with higher body mass index but not with vitamin D level in a Thai population.

Vitamin D deficiency has been linked to hypertension. Although vitamin D deficiency is common in tropical regions, no data on its association with hypertension were available. We randomly selected 137 cases and controls whose plasma in 1985 was available for the assessment of vitamin D status and calculated the odds ratio of having hypertension in 1997. In all, 36% of the participants were vitamin D deficient. The odds ratio of having hypertension was marginally significant for vitamin D deficiency (0.59, P=0.05) and statistically significant for body mass index (BMI)-defined overweight (1.8, P=0.02). The inverse relationship between vitamin D deficiency and hypertension became statistically significant after further adjustment for BMI, high-density lipoprotein cholesterol and triglyceride (0.55, P=0.03). Stepwise regression identified BMI-defined overweight and vitamin D deficiency as the variables of significance in relation to hypertension. Our data suggest that vitamin D deficiency, although not a rarity in Thailand, was not associated with an increased risk of developing hypertension in Thai people.

The relationship of fetuin-A and lactoferrin with bone mass in elderly women.

SUMMARY: The relationships of fetuin-A and lactoferrin to bone-related phenotypes were investigated in elderly women. Fetuin-A was associated not only with bone mineral density (BMD) but also with bone resorption marker suggesting an influence of fetuin-A on osteoclasts. INTRODUCTION: The aim of this study is to investigate the relationship of bone-related phenotypes in elderly women with circulating fetuin-A and lactoferrin. METHODS: Eighty-two elderly women were studied. Serum fetuin-A, lactoferrin, C-terminal telopeptide of type I collagen (CTx), total procollagen type 1 amino-terminal propeptide, and plasma intact parathyroid hormone (PTH) were analyzed. BMD of the lumbar spine at L2-4 and at the femoral neck was measured. RESULTS: Serum fetuin-A was significantly associated with L2-4 BMD (r = 0.23, P < 0.05). After controlling for age and body weight, the association remained statistically significant. There was a significant association between serum fetuin-A and serum CTx (r = -0.37, P < 0.001). The association between fetuin-A and L2-4 BMD no longer existed after controlling for serum CTx. There were positive associations of circulating lactoferrin with plasma PTH (r = 0.24, P < 0.05) and serum CTx (r = 0.26, P < 0.05). No association between serum lactoferrin and BMD at the lumbar spine or femoral neck was detected. CONCLUSIONS: Circulating fetuin-A is related to bone mass and bone resorption markers in elderly women. Lactoferrin, in contrast, is associated only with bone resorption markers.

Differential associations of residual estradiol levels with bone mineral density and serum lipids in postmenopausal women with osteoporosis.

OBJECTIVES: To examine the associations of residual endogenous estradiol (E2) to bone mineral density (BMD) and lipid concentrations in elderly women. METHODS: Subjects consisted of 59 elderly postmenopausal women with vertebral or femoral osteoporosis. BMD was measured at L2-4 and femoral neck by dual-energy X-ray absorptiometry (DEXA). Residual E2 concentrations were assessed by a sensitive radioimmunoassay. Data were expressed as mean +/- S.E.M. RESULTS: The age of the subjects was 65.2 +/- 0.8 years with 18.9 +/- 1.0 years postmenopausal. The mean residual E2 concentration was 6.0 +/- 0.5 pg/ml. There was a correlation between E2 levels and BMD at L2-4 (r = 0.32, P < 0.01) while no association was found at the femoral neck. The association between E2 and L2-4 BMD persisted after adjusting for years since menopause and body weight (r = 0.33, P < 0.05). With regard to serum lipid concentrations, no association of serum total cholesterol, LDL-cholesterol, HDL-cholesterol or triglyceride concentrations with residual E2 was found. CONCLUSIONS: Our findings confirm the role of residual endogenous E2 in the determination of bone mass in postmenopausal women with osteoporosis. The effect of residual E2 appears to be skeletal specific and possess no association with serum lipid concentrations.

Rectal administration of propylthiouracil in hyperthyroid patients: comparison of suspension enema and suppository form.

Previous studies have described the therapeutic effects of propylthiouracil (PTU) and methimazole in normal subjects after rectal suppositories. The goal of our study was to compare the pharmacokinetic and pharmacologic effects of a suppository and suspension form of PTU given per rectum. Fifteen newly diagnosed hyperthyroid patients of both genders (ages 21 to 55 years) were randomly given the drug as follows: group 1 (n = 7), a single enema (400 mg of PTU in 90 mL of sterile water) and group 2 (n = 8), two suppositories of polyethylene glycol base (200 mg of PTU in each). The pharmacokinetic study revealed earlier time to peak levels (T(max)) and significantly greater maximal peak levels (C(max)) in group 1 than in group 2, (85.71 +/- 12.12 minutes vs. 172.5 +/- 26.24 minutes for T(max) and 3.89 +/- 0.34 vs. 2.01 +/- 0.38 microg/mL, p < 0.05 for C(max), respectively). However, the area under the curve (635.16 +/- 105.71 vs. 377.87 +/- 68.09 microg x min/mL) was not statistically different between both groups. Both forms induced a significant decrease in serum free triiodothyronine (FT(3)) levels and an increase in serum rT(3) levels shortly after administration. Four subjects reported a bitter taste 5-10 minutes after receiving the drug. PTU can be effectively absorbed via the rectal route. The enema form appeared to provide better bioavailability than the suppository form. However, both preparations exhibited comparable therapeutic effect.

Effect of estrogen replacement on insulin sensitivity, serum lipid and bone resorption marker in hypogonadal males.

Recent reports of osteoporosis in congenital estrogen deficiency in humans from estrogen resistance or aromatase deficiency have called attention to the importance of estrogen in males. It is the purpose of the present study to evaluate the effects of low- dose estrogen on glucose, lipid and bone metabolism in males with hypogonadism. Nine Thai males with primary or secondary hypogonadism were included in the study. Testosterone was discontinued at least 8 weeks before the study. The subjects received 0.3 mg of conjugated equine estrogen (CEE) daily for 4 weeks. Serum C-terminal telopeptide of type 1 collagen (CTX), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride (TG) and parameters related to insulin sensitivity were measured at baseline and 4 weeks after treatment. Insulin sensitivity was assessed by frequent intravenous glucose tolerance test. The mean age of subjects was 35.77 years (22-70 years). Insulin sensitivity index (SI) did not change significantly after the administration of CEE (P=0.09). Likewise, no change in acute insulin response (AIR(glucose)) was detected. However, glucose effectiveness (SG) significantly decreased after CEE (P<0.05). No significant change in serum TC, LDL-C, HDL-C or TG was detected. In regard to bone turnover, serum CTX significantly decreased after CEE administration (P<0.05). We concluded that low-dose estrogen administration in hypogonadal males for 4 weeks causes a decrease in bone turnover and an increase in glucose effectiveness. No effect on serum lipid concentrations or insulin sensitivity and secretion was detected.

Differences in bone mineral density and lifestyle factors of postmenopausal women living in Bangkok and other provinces.

UNLABELLED: Decreased bone mineral density (BMD) with age is an increasing health problem, especially for postmenopausal women. Multiple factors have been reported to affect BMD including both genetic and environmental factors such as calcium intake and physical activity. For Thailand, people residing in different regions may differ in BMD due to these factors. However, there is a paucity of data concerning this issue. The objectives of this study were to identify the lifestyle factors which may influence BMD and to investigate the association between BMD and these factors in postmenopausal women who have been living in Bangkok and other provinces in Thailand. Subjects consisted of 466 postmenopausal women aged 46-90 years including 236 Bangkokians (116 early postmenopausals and 120 late postmenopausals) and 230 non-Bangkokians (134 early postmenopausals and 96 late postmenopausals). All were healthy and ambulatory. BMD was measured by dual energy X-ray absorptiometry (DEXA, Expert XL). Calcium intake was assessed by food-frequency questionnaire. Data were expressed by mean + /- SEM. There were 22 per cent (n=52), 5.9 per cent (n=14), and 4.2 per cent (n=10) of postmenopausal Bangkokians while 13.9 per cent (n=32), 4.3 per cent (n=10), and 2.2 per cent (n=5) of postmenopausal non-Bangkokians who had low BMD at spine, femoral neck, and at both sites, respectively. Spine BMD (SPBMD) and femoral neck BMD (FNBMD) increased significantly across the quartiles of calcium intake in both groups of subjects (P<0.05) and a significant difference was found between the lowest and the highest quartiles of calcium intake (P<0.05). Moreover, BMD at both regions was shown to be correlated with calcium intake, exercise and sunlight exposure in these subjects (P<0.001). Further analysis revealed higher BMD at spine (0.992 + 0.02 vs 0.945 +/- 0.02 g/cm2, P<0.05) and at femur (0.780 +/- 0.01 vs 0.740 +/- 0.01 g/cm2, P<0.05), calcium intake (348.9 +/- 12.7 vs 316.3 +/- 8.0 mg/day, P<0.05), exercise (2.8 +/- 0.1 vs 2.4 +/- 0.1 h/wk, P<0.001) and sunlight exposure (2.9 +/- 0.06 vs 1.9 +/- 0.04 h/day, P<0.001) were found in late postmenopausal women in other provinces than their counterparts in Bangkok. Nevertheless, no significant difference of BMD at both sites, calcium intake and exercise was found in the early postmenopausal groups of these two areas. CONCLUSIONS: There were significant differences in BMD and lifestyle factors between late postmenopausal women in Bangkok and other provinces. Environmental factors especially calcium intake, exercise and sunlight exposure, may influence BMD in late postmenopausal Thai women.

Biochemical markers of bone turnover and response of bone mineral density to intervention in early postmenopausal women: an experience in a clinical laboratory.

BACKGROUND: Markers of bone formation and resorption may be useful as early indicators of response to therapy. Our aim in this study was to investigate the use of bone markers for monitoring of intervention for bone loss in early postmenopausal women and to assess the relationships between these markers and changes in bone mineral density (BMD). METHODS: Subjects were randomly assigned to the following groups: a control group; a group receiving calcium alone; groups receiving calcium plus low or conventional doses of conjugated equine estrogen; and groups receiving calcium plus low or conventional doses of calcitriol. At baseline and at 1 and 3 months after intervention, we measured serum intact osteocalcin, serum N-terminal midfragment osteocalcin, serum C-terminal telopeptide of type I collagen (CTx), urinary deoxypyridinoline cross-links, and urinary CTX: The BMD of the lumbar spine and the femoral neck was measured at baseline and after 1 and 2 years of intervention. RESULTS: No marker changed significantly in the control group except urinary CTx, which increased at 3 months. Serum CTx decreased in all regimens at 1 or 3 months of intervention. In addition, the changes of all markers at 3 months were inversely associated with the change in the BMD of the lumbar spine at 1 or 2 years (r = -0.144 to -0.314), whereas only the changes of bone resorption markers at 3 months were inversely correlated with the changes in femoral BMD at 1 or 2 years (r = -0.143 to -0.366). CONCLUSIONS: Biochemical markers of bone turnover appear to be of use in assessing early response to therapy. Bone resorption markers, especially serum CTx, are better indicators than bone formation markers for estimating the response to intervention in early postmenopausal women. However, the early changes in bone markers were weakly related to the later changes in BMD.

Association of a T262C transition in exon 1 of estrogen-receptor-alpha gene with skeletal responsiveness to estrogen in post-menopausal women.

Polymorphic genetic markers of estrogen-receptor-alpha (ERalpha) gene studied so far in osteoporosis reside in non-coding region with uncertain functional significance. The purpose of the present study was to search for nucleotides changes in the exon 1 and 5' regulatory region of ERalpha gene, to study the nature of their linkages to the previously reported Pvull polymorphism in intron 1 and their functional significance in postmenopausal osteoporosis. Direct sequencing of exon 1 and promotor region of ERalpha gene revealed a synonymous nucleotide substitution from T to C at position 262, 29 nucleotides downstream from the putative start codon. No nucleotide change was found in the promotor region. Linkage disequilibrium between the T262C polymorphism and the Pvull polymorphism in intron 1 of ERalpha gene was demonstrated in 129 post-menopausal women (p<0.001). After treating 96 post-menopausal with 0.3 mg or 0.625 mg conjugated equine estrogen (CEE) for 2 yr, vertebral bone mineral density (BMD) increased regardless of the T262C genotype. However, with regard to femoral neck BMD, only those subjects that were homozygous for the T262C polymorphism had an increase in femoral BMD (+5.9+/-1.4%, mean+/-SE; p<0.0001). Using analysis of covariance to assess the effects of the T262C polymorphism, the intronic Pvull polymorphism, doses of CEE and the corresponding baseline BMD on the changes in vertebral or femoral BMD after treatments, it was found that the change in vertebral BMD was related only to the baseline BMD (p<0.05). The change in femoral BMD was independently related to the T262C polymorphism (p<0.01) and the baseline femoral BMD (p<0.01). No effect of the Pvull polymorphism or the doses of CEE on femoral BMD was demonstrated. We concluded that the previously described intronic Pvull polymorphism of ERalpha gene is in linkage disequilibrium with a T262C polymorphism in exon 1. This T262C polymorphism appears to be more directly related to the skeletal response after long-term treatment with estrogen.

Prevalence of hypovitaminosis D in elderly women living in urban area of Khon Kaen province, Thailand.

This study included 106 volunteer elderly women who were living in an urban area of Khon Kaen province. The mean (+/-SD) of age and of serum 25(OH)D concentration of these elderly women was 69.42 (+/-6.77) years and 33.32 (+/-7.14) ng/ml respectively. There was a significant inverse relationship between serum 25(OH)D and PTH concentration. Serum PTH concentration started to increase steeply when serum 25(OH)D concentration declined < or = 35 ng/ml and increased significantly when serum 25(OH)D concentration declined < or = 30 ng/ml. Furthermore mean (+/-SD) of serum 25(OH)D concentration in the group of osteopenia and osteoporosis of femoral neck was 35.25 (+/-6.77) and 30.92 (+/-6.49) ng/ml respectively. As a result, the prevalence of hypovitaminosis D in these selected elderly women would be at least 34.9 per cent, or as high as 65.1 per cent.

Association of a G2014A transition in exon 8 of the estrogen receptor-alpha gene with postmenopausal osteoporosis.

We report the association of a newly identified synonymous G2014A single nucleotide polymorphism (SNP) which does not alter the amino acid sequence in exon 8 of the estrogen receptor-alpha (ERalpha) gene with osteoporosis in Thai postmenopausal women. Subjects consisted of 228 postmenopausal women aged more than 55 years divided into two groups--with vertebral or femoral osteoporosis (n = 106) or without osteoporosis (n = 122)--according to bone mineral density (BMD) criteria. The exon 8 G2014A SNP, which is 6 nucleotides upstream from the end of the stop codon, was identified by PCR-RFLP. Data are expressed as the mean and 95% CI. The allele frequency of the G2014A polymorphism was 26.4% in osteoporotic subjects and was significantly higher than that in non-osteoporotic women (15.2%) (p<0.05). By stepwise logistic regression analysis, it was found that the G2014A polymorphism was related to the presence of osteoporosis (odds ratio 2.7 per A allele, 95% CI 1.49-4.76) independently of body weight (odds ratio 0.93 per kg, 95% CI 0.89-0.96) and years since menopause (odds ratio 1.12 per year, 95% CI 1.08-1.19). In a multiple linear regression model, L2-L4 BMD of osteoporotic subjects was associated with body weight (p<0.05), endogenous estradiol levels (p<0.05) and the G2014A genotype (p<0.001), while it was related only to body weight (p<0.05) and estradiol levels in non-osteoporotic women (p<0.05). We conclude that a G2014A SNP in exon 8 of ERalpha is associated with the presence and severity of postmenopausal osteoporosis. Linkage disequilibrium between this polymorphism and the 3'-untranslated region of the ERalpha gene which may participate in the regulation of ERalpha gene expression remains to be determined.

Different mechanism of bone loss in ageing women and men in Khon Kaen Province.

UNLABELLED: The changes of vitamin D status and biochemical markers of bone turnover have been reported with aging. In this study we determined age-related levels of vitamin D and biochemical markers of bone turnover in the general adult population between the ages of 20 and 84 years who were living in Khon Kaen province in northeastern Thailand. Serum 25 hydroxyvitamin D was determined as an indicator of vitamin D status. Serum total alkaline phosphatase and N-terminal mid fragment osteocalcin were measured as biochemical markers of bone formation and serum C-terminal fragment of type I collagen was measured as a marker of bone resorption. The levels of serum 25 hydroxyvitamin D were high in the Khon Kaen population. Men had higher levels of 25 hydroxyvitamin D than did women. However, there were no changes with age in either sex. In women, all biochemical markers of bone turnover increased with age after the fourth decade. The sharp increase was observed in the sixth decade which was around the menopausal age. In contrast, in men all biochemical markers of bone turnover except serum total alkaline phosphatase had a tendency to decrease with age. CONCLUSION: There was no evidence of vitamin D deficiency in a Khon Kaen population. In addition, serum vitamin D levels did not decline with ageing. Women and men showed different changes of biochemical markers of bone turnover with ageing indicating gender difference in the pathogenesis of osteoporosis.

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

OBJECTIVE: An oestrogen-receptor-alpha (ERalpha) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERalpha 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 ERalpha gene polymorphism. PATIENTS AND MEASUREMENTS: Subjects consisted of 124 Thai post-menopausal women. Sixty-three of the women were less than 6 years post-menopausal and 61 were more than 10 years post-menopausal with vertebral or femoral osteoporosis as defined by BMD T-score less than - 2.5. Subjects were randomly allocated to receive 0.3 mg (n = 67) or 0.625 mg (n = 57) of conjugated equine oestrogen (CEE). All subjects also took 5 mg medroxyprogesterone acetate. Vertebral and femoral neck BMD were measured at baseline and 1 year after treatment. Data were expressed as mean +/- SEM. Capital P represents the absence of the restriction site while lower-case p indicates the presence of the restriction site. RESULTS: For subjects on 0.625 mg CEE, BMD at L2-4 increased significantly after 1 year in those with pp (n = 20) Pp (n = 29) and PP genotypes (n = 8) (P < 0.001). However, in subjects on 0.3 mg CEE, BMD at L2-4 increased significantly after 1 year in subjects with Pp (n = 34, + 7.6 +/- 1.5%, P < 0.001) and PP genotypes (n = 13, + 6. 9 +/- 1.0%, P < 0.001), but not in those with pp genotype (n = 20, + 2.3 +/- 2.1%, P = NS). After adjusting for age and years since menopause, the change in vertebral BMD was still lower in those without the P allele compared to those with the P allele (P < 0.05). Femoral BMD did not significantly change regardless of dose of CEE and genotype. CONCLUSIONS: We conclude that ERalpha gene polymorphism affects skeletal response to oestrogen in post-menopausal women. The effect of ERalpha gene polymorphism appears to be site-specific and does not relate to biochemical markers of bone turnover. Determination of ERalpha genotype may help identify post-menopausal women who will have more skeletal benefit from oestrogen therapy.

Prevention of postmenopausal bone loss by low and conventional doses of calcitriol or conjugated equine estrogen.

OBJECTIVES: Estrogen deficiency is the most common cause of postmenopausal osteoporosis and estrogen replacement is well known to retard postmenopausal bone loss. Calcium supplement alone is generally considered to be insufficient for the prevention of bone loss associated with estrogen deficiency while the role of calcitriol is unclear. In the present study we examined the efficacy different doses of estrogen or calcitriol in the prevention of postmenopausal bone loss in Thais. METHODS: The subjects consisted of 146 Thai women no more than 6 years postmenopausal. The subjects were randomly allocated to receive 750 mg supplemental calcium alone, calcium and conjugated equine estrogen (CEE) at 0.3 or 0.625 mg, calcium and calcitriol at 0.25 or 0.5 microg daily. Those receiving CEE also took 5 mg medrogestone for 12 days each month. BMD at L2-4 and femoral neck were measured at baseline 1 year and 2 years after treatments. Data were expressed as mean +/- S.E. RESULTS: Subjects on supplemental calcium alone had approximately 2.5% decreases in L2-4 (P < 0.05) and femoral BMD (P < 0.01) at 2 years. CEE (0.3 mg) resulted in 3.20 +/- 1.2% increase in vertebral BMD (P < 0.05) while no significant change in BMD was demonstrated at the femoral neck. Likewise, 0.625 mg of CEE induced 5.4 +/- 1.4% increase in vertebral BMD at 2 years (P < 0.001) without change in the femoral BMD. In regard to calcitriol, no significant change in vertebral or femoral BMD was demonstrated with either 0.25 or 0.5 microg calcitriol. CONCLUSION: We concluded that calcitriol is effective in the prevention of early postmenopausal bone loss in Thais. It represents an option for the prevention of osteoporosis in postmenopausal women who are contraindicated for estrogen replacement.

Correlation of apolipoprotein E gene polymorphism to serum lipid concentrations in healthy Thais.

This study determined the genotype distribution of apolipoprotein E (apo E) gene and its relation to serum lipids in 217 healthy Thais consisting of 79 males and 138 females. Serum total cholesterol (TC), HDL-cholesterol (HDL-C) and triglyceride (TG) concentrations were determined by enzymatic-colorimetric methods, while serum LDL-cholesterol (LDL-C) levels were calculated using Friedewald formula. Apo E genotypes were determined by PCR-RFLP. Out of 217 subjects, apo E genotype frequencies were 5.5 per cent for E2/E2, 12.4 per cent for E2/E3, 81.1 per cent for E3/E3 and 0.9 per cent for E4/E4. In men, advancing age was associated with increased serum TC (r = 0.28, P < 0.05) and LDL-C (r = 0.27, P < 0.01). Subjects having the E2 allele had lower TC (r = -0.27, P < 0.05) and LDL-C. (r = -0.25, P < 0.05). Age and apo E genotypes were not associated with HDL-C and TG in men. In women, increasing age was related to higher serum TC (r = 0.45, P < 0.001), LDL-C (r = 0.44, P < 0.001), TG (r = 0.40, P < 0.001) and lower HDL-C (r = -0.36, P < 0.001). The presence of E2 allele was related to lower TC (r = -0.24, P < 0.001), LDL-C (r = -0.26, P < 0.001), TG (r = -0.15, P < 0.05) and higher HDL-C (r = 0.20, P < 0.01) independent of age and menopausal status. We concluded that the epsilon 4 allele of apo E gene is rare in Thais. The presence of the epsilon 2 allele is associated with a more favorable lipid profile and there is a sexual dimorphism concerning the effect of apo E genotype on serum HDL-C and TG.

Serum leptin concentrations in relation to body fat, gender, sex hormones and metabolic covariates in Thais.

In the present study, the relation of serum leptin to adiposity, gender and metabolic covariates in normal Thais was examined. Subjects consisted of 224 individuals aged between 20-79 years. Eighty two were men while 142 were women. Data were expressed as mean +/- SEM. Serum leptin was associated with total body fat assessed by dual-energy X-ray absorptiometry in both men (r = 0.80, P < 0.0001) and women (r = 0.73, P < 0.0001). Compared to women, serum leptin concentrations was lower in men (P < 0.0001). The difference still persisted after controlling the adiposity. Compared to premenopausal women, postmenopausal women had higher serum leptin independent of adiposity (P < 0.0001). In men, serum free testosterone was negatively associated with serum leptin (r = -0.36, P < 0.001) while there was no association between serum estradiol and leptin. The relation between serum FT and leptin in men no longer persisted after controlling for adiposity. Body fat was associated with fasting insulin levels in both men (r = 0.26, P < 0.05) and women (r = 0.18, P < 0.05). However, the association between fasting insulin levels and body fat in both men and women no longer existed after adjusting for leptin. We concluded that serum leptin concentrations are associated with total body adiposity and serum leptin may mediate the effect of body fat on insulin sensitivity. There appears to be a sexual dimorphism of serum leptin unrelated to sex hormone status and the amount of body fat.