Anion- and Solvent-Induced Single-Crystal-to-Single-Crystal Transformation within an Iron(II) Triazole System: a Promising Luminescent Probe for CrO42- and Cyano-Containing Molecules.

Anion- and solvent-induced single-crystal-to-single-crystal transformation within an iron(II) triazole system has been generated from {[Fe(TPPT)2Cl2]·CHCl3} n (1a) to [Fe(TPPT)(C2O4)0.5Cl(H2O)] n (1b). Luminescence studies indicated that the resultant 1b can be considered as a promising luminescent probe for CrO42- and cyano molecules.

[Osteoprotegerin gene polymorphism and therapeutic response to alendronate in postmenopausal women with osteoporosis].

OBJECTIVE: To investigate whether the polymorphism of osteoprotegerin (OPG) gene is associated with the change of BMD (bone mineral density) after alendronate therapy in postmenopausal women with osteoporosis and determine the correlation between genotypes and therapeutic effect. METHODS: Eighty postmenopausal osteoporotic patients were recruited with an average age of (64.2 +/- 7.7) years old. Every patient took oral alendronate (Fosamax) 70 mg weekly and Caltrate 600 mg daily for 12 months. At pre- and post-treatment, BMD was measured at lumbar spine 2 - 4 and hip sites. PCR-RFLP was performed for three polymorphisms at the promoter site of OPG gene (A163G, T245G and T950C). RESULTS: One-year therapy was accomplished in 67 patients. Patients with G allele (genotype AG and GG) of site A163G, the baseline BMD of vertebral L2-4, inter-troche and total hip were lower than genotype AA [(0.732 +/- 0.113) g/cm(2) vs (0.819 +/- 0.157) g/cm(2), (0.775 +/- 0.101) g/cm(2) vs (0.843 +/- 0.124) g/cm(2) and (0.667 +/- 0.105) g/cm(2) vs (0.725 +/- 0.091) g/cm(2)]. Patients with G allele (genotype TG and GG) of site T245G, baseline BMD of vertebral L2-4, inter-troche and total hip were lower than genotype TT [(0.723 +/- 0.111) g/cm(2) vs (0.819 +/- 0.155) g/cm(2), (0.776 +/- 0.102) g/cm(2) vs (0.840 +/- 0.124) g/cm(2) and (0.670 +/- 0.109) g/cm(2) vs (0.721 +/- 0.091) g/cm(2)]. After one-year therapy, at site A163G, the percentage of BMD change at inter-troche was higher in genotype AA than in genotypes AG and GG [2.50 (3.47)% vs 0.88% (3.47%)%, P = 0.014]. While at site T245G, the percentage of BMD change at inter-troche and total hip were higher in genotype TT than in genotype TG and GG 2.50% (3.47%) vs 0.61% (3.31%), P = 0.011; 2.72% (2.68%) vs 0.89 (3.01%), P = 0.046]. CONCLUSION: The G allele of sites A163G and T245G may be the risk allele of postmenopausal osteoporosis. Furthermore, patients with genotypes AA (A163G) and (T245G) show a better therapeutic effect to alendronate.

Age-related changes of serum tartrate-resistant acid phosphatase 5b and the relationship with bone mineral density in Chinese women.

AIM: Osteoclastic activity is mainly assessed by measurement of urinary markers (eg C-terminal cross-linked telopeptides of type I collagen, N-terminal crosslinked telopeptides of type I collagen, etc), the levels of which could often be affected by renal clearance. Recently, serum tartrate-resistant acid phosphatase 5b (TRACP5b) has been used as an alternative serum marker to evaluate osteoclastic activity. We investigated the age-related changes of TRACP5b level and its association with bone mineral density (BMD) in Chinese women. METHODS: Seven-hundred and twenty-two Chinese mainland women aged 20-79 years were recruited in the study. Serum TRACP5b level was measured using immunoassay to evaluate the state of bone resorption. Bone mineral density (BMD) (g/cm2) at lumbar spine 1-4 and proximal femur were measured by duelenergy X-ray absorptiometry. RESULTS: The serum TRACP5b level reached a bottom value in premenopausal women aged 30-39, gradually increased in women aged 40-49, rapidly rose in women aged 50-59, and culminated with a maximum value in women aged 60-69 before a slow drop in women aged 70- 79. The average level of TRACP5b was significantly higher in postmenopausal women [(3.29+/-1.07) U/L] than in premenopausal women ([1.70+/-0.59] U/L). The levels of TRACP5b were inversely correlated with BMD at all measured sites (P<0.001). Furthermore, the level of TRACP5b was obviously higher in women with osteoporosis and osteopenia than those with normal bone mass (P<0.001). CONCLUSION: We have established the reference values of serum TRACP5b in Chinese mainland women, and found that postmenopausal women had higher TRACP5b concentration than younger women. The results showed that serum TRACP5b was a sensitive and useful parameter for the evaluation of age-related changes of bone absorption.

[Development of a simple predicting tool for low bone mass of postmenopausal women: a study in Shanghai].

OBJECTIVE: To develop a simple screening tool for low bone mass of postmenopausal women. METHODS: 405 postmenopausal women in Shanghai who visited the department of osteoporosis consecutively, aged 62.8 +/- 8.0 (47 approximately 90), underwent questionnaire survey on the risk factors of osteoporosis and fracture. Dual energy X-ray absorptiometry (DXA) was conducted on the left or right femoral neck to measure the bone mineral density (BMD) to identify osteoporosis (T-score

Association between SNP and haplotypes in PPARGC1 and adiponectin genes and bone mineral density in Chinese nuclear families.

AIM: To assess the contribution of single nucleotide polymorphisms (SNP) and haplotypes in the peroxisome proliferators-activated receptor-gamma co-activator-1 (PPARGC1) and adiponectin genes to normal bone mineral density (BMD) variation in healthy Chinese women and men. METHODS: We performed population-based (ANOVA) and family-based (quantitative trait locus transmission disequilibrium test) association studies of PPARGC1 and adiponectin genes. SNP in the 2 genes were genotyped. BMD was measured using dual-energy X-ray absorptiometry in the lumbar spine and hip in 401 nuclear families with a total of 1260 subjects, including 458 premenopausal women, 20-40 years of age; 401 postmenopausal women (mothers), 43-74 years of age; and 401 men (fathers), 49-76 years of age. RESULTS: Significant within-family association was found between the Thr394Thr polymorphism in the PPGAGC1 gene and peak BMD in the femoral neck (P=0.026). Subsequent permutations were in agreement with this significant within-family association result (P=0.016), but Thr394Thr SNP only accounted for 0.7% of the variation in femoral neck peak BMD. However, no significant within-family association was detected between each SNP in the adiponectin gene and peak BMD. Although no significant association was found between BMD and SNP in the PPARGC1 and adiponectin genes in both men and postmenopausal women, haplotype 2 (T-T) in the adiponectin gene was associated with lumbar spine BMD in postmenopausal women (P=0.019). CONCLUSION: Our findings suggest that Thr394Thr SNP in the PPARGC1 gene was associated with peak BMD in the femoral neck in Chinese women. Confirmation of our results is needed in other populations and with more functional markers within and flanking the PPARGC1 or adiponectin genes region.

[Relationship between the polymorphism of start codon and CDX2 site in vitamin D receptor gene and the effect of calcium supplementation on bone mineral density of postmenopausal women].

OBJECTIVE: To investigate the association of polymorphisms of start codon (Fok I site) and CDX2 binding site in vitamin D receptor gene (VDR) concerned with the effect of calcium supplementation on bone mineral density (BMD) and bone turnover markers of postmenopausal women. METHODS: Two hundreds unrelated postmenopausal women of Han ethnicity in Shanghai were randomly divided into 2 groups of 100 women: high calcium group (1000 mg element calcium and 400 units of vitamin D were given daily for 12 months) and low calcium group (300 mg element calcium and 300 units of vitamin D were given daily for 12 months). BMD and bone turnover markers were measured at baseline and 12 months after calcium supplementation. VDR gene Fok I and CDX2 polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific multiplex PCR, respectively. RESULTS: One hundred and seventy-one women completed 12-month study period. The frequency of VDR Fok I genotypes was 48.0 % for Ff, 31.0 % for FF, and 21.0 % for ff, and the frequency of CDX2 genotypes was 56.7 % for AG, 25.7% for GG, and 17.6% for AA. The frequencies distribution of Fok I and CDX2 alleles in the entire population or in two subgroups all followed the Hardy-Weinberg equilibrium. No significant difference of baseline BMD and bone turnover markers in Fok I genotypes or CDX2 genotypes was observed in the entire population or in two subgroups. Moreover, regardless of calcium supplementation given for 12 months, no significant association was found between Fok I or CDX2 polymorphisms and the endpoint values or percentage changes of any BMD and bone turnover markers in either high calcium group or low calcium group. CONCLUSION: There is no significant relationship between VDR gene Fok I or CDX2 polymorphisms and the effect of high or low doses calcium supplementation on BMD and bone turnover markers in Shanghai postmenopausal women of Han ethnicity.

A20 overexpression under control of mouse osteocalcin promoter in MC3T3-E1 cells inhibited tumor necrosis factor-alpha-induced apoptosis.

AIM: To construct an A20 expression vector under the control of mouse osteocalcin promoter (OC-A20), and investigate osteoblastic MC3T3-E1 cell line, which stably overexpresses A20 protein prevented tumor necrosis factor (TNF)-alpha-induced apoptosis. METHODS: OC-A20 vector was constructed by fusing a fragment of the mouse osteocalcin gene-2 promoter with human A20 complementary DNA. Then the mouse MC3T3-E1 cell line, stably transfected by A20, was established. The expression of A20 mRNA and A20 protein in the cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To determine the specificity of A20 expression in osteoblast, the mouse osteoblastic MC3T3-E1 cell line and mouse embryo fibroblast NIH3T3 cell line were transiently transfected with OC-A20. The anti-apoptotic role of A20 in MC3T3-E1 cells was determined by Flow cytometric analysis (FACS), terminal dUTP nick endo-labeling (TUNEL) and DNA gel electrophoresis analysis (DNA Ladder), respectively. RESULTS: Weak A20 expression was found in MC3T3-E1 cells with the primers of mouse A20. A20 mRNA and A20 protein expression were identified in MC3T3-E1 cells transfected with OC-A20 using RT-PCR and Western blot analysis. Only A20 mRNA expression was found in MC3T3-E1 cell after MC3T3-E1 cells and NIH3T3 cells were transient transfected with OC-A20. A decrease obviously occurred in the rate of apoptosis in the OC-A20 group compared with the empty vector (pcDNA3) group by FACS (P< 0.001). A significant increase in TUNEL positive staining was found in the pcDNA group compared with OC-A20 group (P< 0.001). Simultaneously, similar effects were demonstrated in DNA gel electrophoresis analysis. CONCLUSION: We constructed an osteoblast-specific expression vector that expressed A20 protein in MC3T3-E1 cells and confirmed that A20 protects osteoblast against TNF-alpha-induced apoptosis.

Bone mineral density of the spine and femur in healthy Chinese men.

AIM: To establish bone mineral density (BMD) reference database in healthy Chinese men of Han ethnicity, and to estimate the prevalence of osteoporosis in the population. METHODS: The BMD in the lumbar spine 1-4 (L1-4) and proximal femur was measured using dual energy X-ray absorptiometry in a total of 1 385 healthy Chinese men of Han ethnicity aged 20-89 years old in Shanghai. RESULTS: The highly significant negative correlation between age and BMD at any sites of proximal femur was found in the studied population, wheras no correlation between age and BMD at lumbar spine was observed. The peak BMD of the lumbar spine and any sites of hip in Chinese men was defined as the mean BMD for the subjects aged 20-89 years. According to World Health Organization (WHO) criteria, the BMD cut-off values for osteoporosis of the L1-4, total hip, femoral neck, trochanter and intertrochanter in Chinese men are 0.719, 0.638, 0.575, 0.437 and 0.725 g/cm(2), respectively. Using the current Chinese reference data, the prevalence of osteoporosis at the L1-4, total hip, femoral neck, trochanter and intertrochanter is 5.4%, 3.8%, 6.3%, 1.8% and 2.8% in 1 084 men aged 50 years or older, respectively. However, using a database for US non-Hispanic white men (NHANES III), the prevalence of osteoporosis or osteopenia at any sites of the hip was significantly higher than that while using the current Chinese reference data. CONCLUSION: The BMD reference database was established in healthy Chinese men of Han ethnicity, and will facilitate more accurate diagnosis of osteoporosis in Chinese men.

[Do the premenopausal daughters of women with postmenopausal osteoporosis have lower peak bone mass?].

OBJECTIVE: To determine whether premenopausal daughters of women with postmenopausal osteoporosis have lower peak bone mass than the daughters of normal women the same age, and to analyze the related risk factors affecting bone mass variation. METHODS: 126 pairs of mother with postmenopausal osteoporosis and her premenopausal daughter, and 136 pairs of normal postmenopausal mother and her premenopausal daughter selected for 410 core families including one healthy premenopausal daughter aged 20 - 40, all of Han ethnicity living in Shanghai recruited by advertisement and lectures. A questionnaire survey was conducted to investigate their dietary custom, Dual-energy X-ray absorptiometry at lumber spine 1 - 4 (L(1 - 4)) and proximal femur was conducted to measure the values of bone mineral density (BMD). RESULTS: The BMD values in L(1 - 4), femoral neck, and greater trochanter of the daughters of mothers with osteoporosis were 0.68 g/cm(2) +/- 0.07 g/cm(2), 0.59 g/cm(2) +/- 0.08 g/cm(2), and 0.47 g/cm(2) +/- 0.07 g/cm(2) respectively, all significantly lower than those of the daughters of normal mothers (0.86 g/cm(2) +/- 0.14 g/cm(2), 0.70 g/cm(2) +/- 0.11 g/cm(2), and 0.57 g/cm(2) +/- 0.10 g/cm(2) respectively, all P < 0.001). The average body weight of the daughters of mothers with osteoporosis was lighter then that of the daughters of normal mothers by 4.8% (P < 0.05). Multivariate regression analysis showed that age, body height, age of menarche, and milk intake were not influencing factors of BMD value, however, body weight was most significantly associated with BMD of the premenopausal daughters, contributing to the BMD variation at L(1 - 4), femoral neck, and greater trochanter by 9.4%, 16.5%, and 16.6% respectively. When body weight was excluded in the model, lower BMD of mother became the most important factors affecting the BMD variation, contributing to the BMD variation at L(1 - 4), femoral neck, and greater trochanter by 5.1%, 5.3%, and 4.2% respectively. CONCLUSION: The daughters of mothers with osteoporosis have reduced peak bone mass. It is likely due to the lower body weight of the daughter and the lower bone mass of the mother.

Association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride on bone mineral density and bone turnover markers in postmenopausal women with osteoporosis.

OBJECTIVE: To investigate the association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride(RLX) on bone mineral density (BMD) and bone turnover markers in postmenopausal women with osteoporosis. METHODS: A total of 68 unrelated postmenopausal women with osteoporosis of Han ethnicity aged 47-74 years were randomly divided into 2 groups of 34 women: RLX group (60 mg were given daily for 12 months) and placebo group. BMD and bone turnover markers were measured at baseline, 6 and 12 months after treatment. The polymorphisms of Xba I and Pvu II sites in estrogen receptor 1 gene(ESR1), Ras I site in ESR2 gene, and start codon (Fok I) and CDX2 binding sites in vitamin D receptor gene (VDR) were analyzed. RESULTS: A total of 58 patients completed 12 months of study period. By the end of study, the increased percentage of BMD in lumbar spine 2-4 (L2-4), total hip, and trochanter were found significantly different between RLX group and placebo group(P<0.05), and the decreased percentage of C-telopeptide and osteocalcin were significantly different between the two groups (P<0.01). The BMD of total hip and trochanter of women with FF genotypes of VDR Fok I site were decreased by 1.98%+/-4.86% and 2.26%+/-4.73% respectively in the RLX group, but those of women with Ff/ff genotypes were increased by 2.52%+/-2.75% and 2.74 %+/-2.97%, respectively(P<0.05). Moreover, the total hip BMD of women with PP/Pp genotypes of ESR1 Pvu II site was increased by 2.12%+/-2.78%, and of women with pp genotype it was decreased by 1.34%+/-3.73%(P<0.05). However, no significant association was observed of the polymorphisms of five sites with the changes of BMD and bone turnover markers in the placebo group. CONCLUSION: The effect of RLX on BMD in postmenopausal women with osteoporosis is regulated by the polymorphisms of Fok I of VDR gene and Pvu II of ESR1 gene. The study is valuable to select this drug according to genotype of patients in clinical.

Association of polymorphisms in low-density lipoprotein receptor-related protein 5 gene with bone mineral density in postmenopausal Chinese women.

AIM: To investigate the possible association of Q89R, N740N and A1330V polymorphisms in low-density lipoprotein receptor-related protein 5 (LRP5) gene with bone mineral density (BMD) in postmenopausal Chinese women. METHODS: Q89R, N740N and A1330V genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 647 unrelated healthy postmenopausal Han Chinese women aged 43-76 years in Shanghai. BMD at lumbar spine 1-4 and the left proximal femur including the femoral neck, trochanter and Ward's triangle were measured by dual-energy X-ray absorptionmetry in all subjects. RESULTS: The distribution of the Q89R, N740N and A1330V genotypes in this population was as follows: QQ 80.5%, QR 18.7%, and RR 0.8%; TT 66.9%, TC 31.1%, and CC 2.0%; AA 68.0%, AV 29.7%, and VV 2.3%. The frequencies of the Q89R, N740N and A1330V genotypes and alleles did not deviate from the Hardy-Weinberg equilibrium. We found that the Q89R and A1330V polymorphisms were in linkage disequilibrium in our population (kappa2=13.50, P<0.01). Both before and after adjusting for age, years since menopause, height, and weight, the Q89R or N740N genotypes were significantly associated with BMD at the femoral neck (P<0.05). Subjects with the Q89R QQ genotype or the N740N TT genotype had a significantly higher BMD at the femoral neck, compared with those with the QR/RR or TC/CC genotypes, respectively. No significant association was found between A1330V polymorphism and BMD at any site. CONCLUSION: Our findings suggest that the LRP5 gene is a candidate for the genetic determination of BMD in postmenopausal Chinese women.

[Association of Xba I, Pvu II, and Bst U I polymorphisms of estrogen receptor-alpha gene with bone mass in men].

OBJECTIVE: To investigate the association of polymorphism in estrogen receptor-alpha (ER-alpha ) gene with bone mineral density(BMD) in men. METHODS: The ER-alpha Xba I, Pvu II and Bst UI genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) in 388 unrelated healthy men who were 46-80 years old and were of Han nationalities in Shanghai city. Bone mineral densities (BMD, g/cm(2)) at lumbar spines 1-4 (L(1-4)) and at any sites of proximal femur, including femoral neck (Neck), trochanter (Troch) and Ward's triangle (Ward's) were measured by duel-energy X-ray absorptiometry. RESULTS: The frequencies distribution of Xba I and Pvu II alleles and genotypes in this cohort all followed the Hardy-Weinberg equilibrium. No Bst UI polymorphic site in ER-alpha gene was found in total samples. All subjects were of BB genotype. No significant association was found between Xba I genotype and BMD at any skeleton sites. The significant association was found between Pvu II genotype and BMD at L(1-4) and Ward's triangle site (P< 0.05). Compared against men with PP and pp genotype, men with Pp genotype had significantly higher mean BMD at L(1-4) and Ward's triangle site (P< 0.05). CONCLUSION: This study suggests that Bst UI polymorphism in ER-alpha gene may be absent or rare in Chinese Han population. Pvu II polymorphism possibly influences the loss of trabecular bone mass in old men.

No major effect of the insulin-like growth factor I gene on bone mineral density in premenopausal Chinese women.

Osteoporosis is a major public health problem, mainly characterized by low bone mineral density (BMD). BMD is a complex trait that is determined by multiple genes. Insulin-like growth factor I (IGF-I) is an important growth factor of bone and thus IGF-I gene has been considered as an attractive candidate gene for osteoporosis. A few studies on the relationship between variants of the IGF-I gene and BMD variation, via traditional association and/or linkage methods, have yielded conflicting results. In this study, we simultaneously tested association and/or linkage of a cytosine-adenine (CA) repeat polymorphism at 1 kb upstream of the transcription initiation site of the IGF-I gene with BMD variation in a large cohort of premenopausal Chinese women. A total of 1263 subjects from 402 Chinese nuclear families were examined. Each family consists of both parents and at least one daughter aged between 20 and 45 years. BMDs (g/cm(2)) at the lumbar spine and hip were measured using dual-energy X-ray absorptiometry (DXA). Applying the QTDT (quantitative transmission disequilibrium tests) progam, we did not find significant evidence of association or linkage between the CA repeat polymorphism of the IGF-I gene and BMD variation at any skeletal site. Our data do not support the IGF-I gene having major effect on BMD variation in premenopausal Chinese women.

Association of estrogen receptor-alpha and vitamin D receptor genotypes with therapeutic response to calcium in postmenopausal Chinese women.

AIM: To investigate the correlation between calcium treatment in postmenopausal women and estrogen receptor-alpha (ER-alpha) Xba I and Pvu II genotype and vitamin D receptor (VDR) Apa I genotype. METHODS: One hundred fifteen postmenopausal Chinese women of Han population were enrolled and treated with calcichew-D3 (1000 mg calcium and 400 U vitamin D3) daily for 1 year. At entry and after 1 year treatment, the bone mineral density (BMD), serum and urinary bone turnover biochemical markers were evaluated. ER-alpha and VDR genotype were analyzed using PCR-restriction fragment length polymorphism. RESULTS: After 1 year of calcium supplementation, a significant increase of BMD and a marked reduction in serum ALP and PTH levels, and a significant increase of serum 25-(OH) vitamin D level were observed (P<0.01 or P<0.05). At entry and after 1 year of treatment, no significant association was found between Xba I, Pvu II, and Apa I genotypes and BMD in L1-4, Neck, and Troch, and all bone turnover marker levels. However, the percentage of change (median, QR) in Neck BMD was significantly different in homozygous XX [-4.14 (from -6.54 to -1.34)] in comparison with Xx [1.72 (from -1.12 to 3.20)] (P<0.001) or xx [1.22 (from -1.74 to 3.06)] Xba I ER-alpha genotype (P=0.001). CONCLUSION: Women with ER-alpha Xba I genotype XX may have a higher risk of relatively fast bone mass loss in femoral neck after menopause and that they may have a poor responsiveness to calcium supplementation. The changes in BMD are not associated with ER-alpha Pvu II genotype and VDR Apa I genotype after 1 year of calcium supplementation.

Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis: a multi-center, randomized, placebo-controlled clinical trial.

BACKGROUND: Raloxifene has been approved for prevention and treatment of postmenopausal osteoporosis in Caucasian women. It also has some positive effects on serum lipids in Caucasians. The objective of this study was to determine the effect of raloxifene hydrochloride on lumbar spine and total hip bone mineral density (BMD), bone metabolism, and serum lipids in Chinese postmenopausal women with osteoporosis. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled clinical trial in which 204 postmenopausal Chinese women with osteoporosis were assigned to receive raloxifene (60 mg) or placebo treatment daily for 12 months. BMD, serum bone metabolism markers, and serum lipids were measured before and after drug administration. BMD was measured by Dual-Energy X-Ray Absorptiometry (DEXA) and bone metabolism markers were analyzed by one-step enzyme-linked immunosorbent assay. Serum lipids were measured by enzymatic analysis. RESULTS: At the end of the 12-month study, lumbar spine BMD increased in both groups with a mean increase of (3.3 +/- 4.8)% in the raloxifene group and (1.0 +/- 4.9)% in the placebo group (P < 0.001). There was a mean increase in total hip BMD of (1.4 +/- 4.8)% in the raloxifene group and a mean decrease of (0.9 +/- 5.0)% in the placebo group (P < 0.001). No subject in the raloxifene group had a new vertebral fracture and 5 placebo subjects had new fractures (P > 0.05). In the raloxifene group, the median decreases in the biochemical markers of bone metabolism serum osteocalcin and C-telopeptide were 41.7% and 61.5%, respectively. These changes were statistically significant compared with those in the placebo group (10.6% and 35.6%, P < 0.001, respectively). Both total cholesterol and low-density lipoprotein cholesterol decreased significantly in the raloxifene group compared with those in the placebo group (P < 0.001, respectively) and there was no significant effect of raloxifene on high-density lipoprotein cholesterol and triglycerides compared with placebo. CONCLUSIONS: Raloxifene 60 mg/d for 12 months significantly increases lumbar spine and total hip BMD, significantly decreases bone turnover, and has favourable effects on serum lipids in Chinese postmenopausal women with osteoporosis.

Lack of association between the HindIII RFLP of the osteocalcin (BGP) gene and bone mineral density (BMD) in healthy pre- and postmenopausal Chinese women.

In Caucasian populations, the polymorphic restriction endonuclease HindIII marker of the osteocalcin (also known as BGP, for bone Gla protein) gene has recently been reported to be associated with bone mass, a major risk determinant of osteoporosis. In this study, we investigated the relationship between the BGP HindIII polymorphism and bone mineral density (BMD) in 388 premenopausal (31.18 +/- 5.92 years) and 169 postmenopausal (58.90 +/- 6.27 years) Chinese women. The BMD of spine and hip was measured by dual-energy X-ray absorptiometry (DEXA). All the study subjects were genotyped at the HindIII site of the BGP gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) detecting methods. The BGP alleles were designated according to the absence ( H) or presence ( h) of the HindIII restriction site. We did not find any significant difference in spine and hip BMD across BGP genotypes in either pre- or postmenopausal women or the combined group. Our result is not consistent with recent reports that the HindIII marker of the BGP gene is associated with osteoporosis. The different findings may reflect inter-population differences in the association (i.e., linkage disequilibrium) of molecular markers with BMD, and indicate the limit of using the HindIII marker of the BGP gene as a genetic marker to discern women susceptible to low BMD and thus osteoporosis in Chinese.

[Effect of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis].

OBJECTIVE: To determine the effect of raloxifene hydrochloride (RLX) on the lumbar spine and total hip bone mineral density (BMD), bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis. METHODS: 204 Chinese postmenopausal women with osteoporosis from 3 hospitals in Beijing and Shanghai were randomly divided into 2 groups of 102 women: RLX group (RLX of the dosage of 60 mg/day was given for 12 months) and placebo group. In addition, 500 mg of elemental calcium and 200 units of vitamin D were given daily to all women. BMD, serum bone markers and lipids were measured before and after drug administration. The BMD of lumber spine and hip was measured by dual-energy X-ray absorptiometry (DEXA). Serum bone gamma-carboxyglutamic acid-containing protein (BGP) and C-teloppeptide were analyzed by one-step ELISA. Serum lipids were measured by enzymatic method. RESULTS: By the end of the 12-month study period, the lumbar spine BMD was increased by 3.3% +/- 4.8% in the RLX group and 1.0% +/- 4.9% in the placebo group (P < 0.001); the hip BMD was increased by 1.4% +/- 4.8%in the RLX group and decreased by 0.9% +/- 5.0% in the placebo group (P < 0.01). New vertebral fracture occurred in none of the subjects in the RLX group and in 5 subjects of the placebo group (P = 0.059). The serum BGP and CTX decreased by 41.7% and 61.5% respectively in the RLX group, both significantly more than those in the placebo group (10.6% and 35.6% respectively, both P < 0.001). Both the total cholesterol and low-density lipoprotein cholesterol were significantly lower in the RLX group than in the placebo group (both P < 0.001), however, there were no significant differences in high-density lipoprotein cholesterol and triglycerides between these two groups. One subject in the RLX group and 5 subjects in the placebo group discontinued the study due to adverse events. There were no differences in the number of subjects with hot flushes (3 in the RLX group and 1 in the placebo group) and the number of subjects with leg cramps (9 in the RLX group and 4 in the placebo group). No venous thromboembolic event was reported. CONCLUSION: RLX of the dosage of 60 mg/day for 12 months significantly increases the lumbar spine and total hip bone BMD, significantly decreases bone turnover and has favorable effects on serum lipids in Chinese postmenopausal women with osteoporosis.

Association of vitamin D receptor and estrogen receptor-alpha gene polymorphism with peak bone mass and bone size in Chinese women.

AIM: To investigate if vitamin D receptor (VDR) gene Apa I polymorphism and estrogen receptor-alpha (ER-alpha) gene Pvu II, Xba I polymorphisms are related to bone mineral density (BMD), bone mineral content (BMC) and bone size in premenopausal Chinese women. METHODS: The VDR Apa I genotype and ER-alpha Pvu II, Xba I genotype were determined by PCR-restriction fragment length polymorphism (RFLP) in 493 unrelated healthy women aged 20-40 years of Han nationality in Shanghai city. BMD (g/cm(2)), BMC (g), and bone areal size (BAS, cm(2) ) at lumbar spine 1-4 (L(1-4)) and proximal femur (femoral neck, trochanter and Ward's triangle) were measured by duel-energy X-ray absorptionmetry. RESULTS: All allele frequencies did not deviate from Hardy-Weinberg equilibrium. After phenotypes were adjusted for age, height, and weight, a significant association was found between VDR Apa I genotype and BMC variation at L(1-4) and Ward's triangle (P<0.05), but not in BMD or BAS at lumbar spine and proximal femur. ER-a Pvu II, Xba I genotype was not related to BMC, BMD, and BAS at all sites. CONCLUSION: The study suggested that Apa I polymorphism in VDR gene may influence on attainment and maintenance of peak bone mass in premenopausal Chinese women.

A major gene model of adult height is suggested in Chinese.

Adult height (stature), as a complex quantitative trait, has been studied in different populations. However, few genetic studies on height were performed on the Chinese, the largest population in the world. In this study, familial correlation and segregation analyses were carried out for adult height in a Chinese sample composed of 385 nuclear families with a total of 1,169 informative individuals. The results suggest that a major gene with a recessive effect accounts for about 17.2% of the total adult height variation in the Chinese. Significant familial residual effects are found. The heritability (+/-SE) of height is estimated to be 0.647 (+/-0.122). This study, for the first time, provides evidence for the high degree of genetic determination of adult height in the Chinese population and furnishes a valuable reference for further mapping and identification of adult height genes in the Chinese.

Evidence for a major gene underlying bone size variation in the Chinese.

Osteoporosis is a major public health problem defined as a loss of bone strength, of which bone size is an important determinant. In the present study, familial correlation and segregation analyses for the spine and hip bone sizes were performed for the first time in a Chinese sample composed of 393 nuclear families with a total of 1,193 individuals. The results indicate a major gene of codominant inheritance for spine bone size; however, there is no evidence of a major gene influencing hip bone size. Significant familial residual effects are found for both traits, suggesting their polygenic inheritance. Heritability estimates (+/-SE) for spine and hip bone size were 0.62 (0.13) and 0.59 (0.12), respectively. Sex and age differences in genotype-specific average bone size were observed. Compared with our previous study on bone mineral density (BMD) in the same population, this study suggests that genetic determination of bone size may be different from that of BMD, and thus studying bone size as one surrogate phenotype for osteoporotic fractures may be necessary.