Association between BMI and osteoporotic fractures at different sites in Chinese women: a case-control retrospective study in Changsha.

BACKGROUND: Osteoporotic fractures are a growing problem in an aging society. The association between body mass index (BMI) and osteoporotic fractures varies by fracture site and ethnicity. Limited knowledge exists regarding this association in native Chinese, particularly utilizing local databases as reference sources. OBJECTIVE: To investigate the association between BMI and osteoporotic fractures at different sites in Chinese women. METHODS: Three thousand ninety-eight female patients with radiographic fractures and 3098 age- and sex-matched healthy controls without fractures were included in the study. Both of them underwent assessment using dual-energy X-ray absorptiometry (DXA), with BMD measurements calculated using our own BMD reference database. Participants were classified into underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24.0 kg/m2), overweight (24 ≤ BMI < 28 kg/m2) and obese (BMI ≥ 28 kg/m2) according to the Chinese BMI classification standard. RESULTS: There were 2296 (74.1%) vertebral fractures, 374 (12.1%) femoral neck fractures, and 428 (13.8%) other types of fractures in the case group. Bone mineral density (BMD) was almost lower in the fracture groups compared to the control groups (p = 0.048 to < 0.001). Compared with normal weight, underweight had a protective effect on total [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.49 -0.75; P< 0.001], and lumbar fractures (OR = 0.52; 95% CI, 0.41 - 0.67; P < 0.001), while obesity was associated with an increased risk for total (OR = 2.26; 95% CI, 1.85 - 2.76; P < 0.001), lumbar (OR = 2.17; 95% CI, 1.72 - 2.73; P < 0.001), and femoral neck fractures (OR = 4.08; 95% CI, 2.18 - 7.63; P < 0.001). Non-linear associations were observed between BMI and fractures: A J-curve for total, lumbar, and femoral neck fractures, and no statistical change for other types of fractures. Underweight was found to be a risk factor for other types of fracturess after adjusting for BMD (OR = 2.29; 95% CI, 1.09 - 4.80; P < 0.001). Osteoporosis and osteopenia were identified as risk factors for almost all sites of fracture when compared to normal bone mass. CONCLUSIONS: Underweight has a protective effect on total and lumbar spine fractures in Chinese women, while obesity poses a risk factor for total, lumbar, and femoral neck fractures. The effect of BMI on fractures may be mainly mediated by BMD.

SP-141 targets Trs85 to inhibit rice blast fungus infection and functions as a potential broad-spectrum antifungal agent.

Rice blast is a devastating disease worldwide, threatening rice production and food security. The blast fungus Magnaporthe oryzae invades the host via the appressorium, a specialized pressure-generating structure that generates enormous turgor pressure to penetrate the host cuticle. However, owing to ongoing evolution of fungicide resistance, it is vitally important to identify new targets and fungicides. Here, we show that Trs85, a subunit of the transport protein particle III complex, is essential for appressorium-mediated infection in M. oryzae. We explain how Trs85 regulates autophagy through Ypt1 (a small guanosine triphosphatase protein) in M. oryzae. We then identify a key conserved amphipathic α helix within Trs85 that is associated with pathogenicity of M. oryzae. Through computer-aided screening, we identify a lead compound, SP-141, that affects autophagy and the Trs85-Ypt1 interaction. SP-141 demonstrates a substantial capacity to effectively inhibit infection caused by the rice blast fungus while also exhibiting wide-ranging potential as an antifungal agent with broad-spectrum activity. Taken together, our data show that Trs85 is a potential new target and that SP-141 has potential for the control of rice blast. Our findings thus provide a novel strategy that may help in the fight against rice blast.

Association of follicle-stimulating hormone with bone turnover markers and bone mineral density in Chinese women across the menopausal transition.

BACKGROUND: Elevated follicle-stimulating hormone (FSH) is associated with an increased risk of postmenopausal osteoporosis. This study investigated the association of serum FSH with bone turnover markers (BTMs) and bone mineral density (BMD) in healthy women undergoing menopausal transition. METHODS: A total of 487 healthy women (age 35-65 years, 50 ± 8.5 years) were enrolled in this study. Serum FSH, BTMs, and BMD at lumbar spine and total hip were measured in these subjects. RESULTS: Follicle-stimulating hormone was positively correlated with various BTMs (r = 0.339-0.583, all p < 0.001) and negatively correlated with lumbar spine and total hip BMD (r = -0.629 and -0.514, all p < 0.001). After adjusting for age and body mass index, the partial correlation coefficients of FSH with BTMs and BMD remained significant. Estimating from the regression equation, for every 10 IU/L increase in serum FSH, BTMs increased by 0.38-3.6 units, and BMD decreased by 0.03-0.05 g/cm2 , respectively. Multiple linear regression analysis showed that FSH was a positive factor for serum bone-specific alkaline phosphatase, osteocalcin, and N-telopeptide of collagen type 1 (ß = 0.188-0.403, all p < 0.001), and a negative factor for lumbar spine BMD and serum C-telopeptide of collagen type 1 (ß = -0.629 and -0.183, all p < 0.001). CONCLUSIONS: This study suggests that serum FSH levels are an independent risk factor for BTMs and BMD in menopause-transitioning women, particularly for serum BAP and lumbar spine BMD.

MoVast2 combined with MoVast1 regulates lipid homeostasis and autophagy in Magnaporthe oryzae.

Macroautophagy/autophagy is an evolutionarily conserved biological process among eukaryotes that degrades unwanted materials such as protein aggregates, damaged mitochondria and even viruses to maintain cell survival. Our previous studies have demonstrated that MoVast1 acts as an autophagy regulator regulating autophagy, membrane tension, and sterol homeostasis in rice blast fungus. However, the detailed regulatory relationships between autophagy and VASt domain proteins remain unsolved. Here, we identified another VASt domain-containing protein, MoVast2, and further uncovered the regulatory mechanism of MoVast2 in M. oryzae. MoVast2 interacted with MoVast1 and MoAtg8, and colocalized at the PAS and deletion of MoVAST2 results in inappropriate autophagy progress. Through TOR activity analysis, sterols and sphingolipid content detection, we found high sterol accumulation in the ΔMovast2 mutant, whereas this mutant showed low sphingolipids and low activity of both TORC1 and TORC2. In addition, MoVast2 colocalized with MoVast1. The localization of MoVast2 in the MoVAST1 deletion mutant was normal; however, deletion of MoVAST2 leads to mislocalization of MoVast1. Notably, the wide-target lipidomic analyses revealed significant changes in sterols and sphingolipids, the major PM components, in the ΔMovast2 mutant, which was involved in lipid metabolism and autophagic pathways. These findings confirmed that the functions of MoVast1 were regulated by MoVast2, revealing that MoVast2 combined with MoVast1 maintained lipid homeostasis and autophagy balance by regulating TOR activity in M. oryzae.

Effect of Body Surface Area on Severe Osteoporotic Fractures: A Study of Osteoporosis in Changsha China.

Clinical vertebral fractures and femoral neck fractures are severe osteoporotic fractures that increase morbidity and mortality. Anthropometric variables are associated with an increased risk of osteoporotic fractures, but it is not clear whether body surface area (BSA) has an effect on clinically severe osteoporotic fractures. The study included total of 3,694 cases of clinical vertebral fractures and femoral neck fractures (2,670 females and 1,024 males) and 3,694 controls without fractures who were matched with the cases by sex and age. There was a significant positive correlation between BSA and bone mineral density (BMD) in female and male fracture patients (females: r = 0.430-0.471, P < 0.001; males: r = 0.338-0.414, P < 0.001). There was a significant systematic increase in BMD in both genders at various skeletal sites, grouped by BSA quartile. The osteoporosis rates of the lumbar spine (97.9%), femoral neck (92.4%) and total hip (87.1%) in the female Q1 group were significantly higher than those in the Q4 group (P < 0.001), which were 80.0%, 57.9% and 36.9%, respectively, in the Q4 group; the osteoporosis rates of the lumbar spine, femoral neck, and total hip were 53.9%, 59.4%, and 36.3% in the male Q1 group, and 15.2%, 21.9%, and 7.03% in the Q4 group, which were significantly lower than those in the Q1 group (P < 0.001). In age-adjusted Cox regression models, the risk of fracture in the remaining three groups (Q2, Q3, and Q4) for weight, BMI, and BSA for both genders, compared with the highest quartile (Q1 by descending quartile stratification) were significantly higher. In models adjusted for age and BMD, only men in the BSA Q3 (HR = 1.55, 95% CI = 1.09-2.19) and BSA Q4 groups (HR = 1.41, 95% CI = 1.05-1.87) had significantly higher fracture risks. In models adjusted for age, height, weight, BMI, and BSA, low BMD was the greatest fracture risks for both sexes. Our results showed that BSA was closely related to BMD, prevalence of osteoporosis, and fracture risk, and that a decline in BSA may be a new potential risk factor for osteoporotic fractures in Chinese men.

MoOpy2 is essential for fungal development, pathogenicity, and autophagy in Magnaporthe oryzae.

The development and pathogenicity of the fungus Magnaporthe oryzae, the causal agent of destructive rice blast disease, require it to perceive external environmental signals. Opy2, an overproduction-induced pheromone-resistant protein 2, is a crucial protein for sensing external signals in Saccharomyces cerevisiae. However, the biological functions of the homologue of Opy2 in M. oryzae are unclear. In this study, we identified that MoOPY2 is involved in fungal development, pathogenicity, and autophagy in M. oryzae. Deletion of MoOPY2 resulted in pleiotropic defects in hyphal growth, conidiation, germ tube extension, appressorium formation, appressorium turgor generation, and invasive growth, therefore leading to attenuated pathogenicity. Furthermore, MoOpy2 participates in the Osm1 MAPK pathway and the Mps1 MAPK pathway by interacting with the adaptor protein Mst50. The interaction sites of Mst50 and MoOpy2 colocalized with the autophagic marker protein MoAtg8 in the preautophagosomal structure sites (PAS). Notably, the ΔMoopy2 mutant caused cumulative MoAtg8 lipidation and rapid GFP-MoAtg8 degradation in response to nitrogen starvation, showing that MoOpy2 is involved in the negative regulation of autophagy activity. Taken together, our study revealed that MoOpy2 of M. oryzae plays an essential role in the orchestration of fungal development, appressorium penetration, autophagy and pathogenesis.

Relationship between bone mineral density and fragility fracture risk: a case-control study in Changsha, China.

BACKGROUND: Fragility fracture is associated with bone mineral density (BMD), and most databases used in related researches are instrument-matched. Little is known about the relationship between BMD and fragility fracture risk of native Chinese, especially using local databases as reference databases. OBJECTIVE: To investigate relationship between BMD and risk of fragility fracture in native China. METHODS: 3,324 cases, including 2,423 women (67.7 ± 8.9 years) and 901 men (68.4 ± 11.6 years) having radiological fragility fractures and 3,324 age- and gender-matched controls participated in the study. We measured BMD at posteroanterior spine and hip using dual-energy X-ray absorptiometry (DXA), calculated BMD measurement parameters based on our own BMD reference database. RESULTS: BMDs and mean T-scores were lower in case group (with clinical fragility) than in control group (without clinical fragility). In patients with fragility fractures, prevalence of lumbar osteoporosis, low bone mass, and normal BMD were 78.9 %, 19.3 %, and 1.8 %, respectively, in women, and 49.5, 44.8 %, and 5.7 %, respectively, in men. In hip, these prevalence rates were 67.2 %, 28.4 %, and 4.4 % in females, and 43.2 %, 45.9 %, and 10.9 % in males, respectively, showing differences between females and males. Multivariate Cox regression analysis showed that after adjusting age, height, weight, and body mass index, fracture hazard ratio (HR) increased by 2.7-2.8 times (95 % CI 2.5-3.1) and 3.6-4.1 times (95 %CI 3.0-5.1) for women and men respectively with decreasing BMD parameters. In both sexes, risk of fragility fracture increased approximately 1.6-1.7 times (95 % CI 1.5-1.8) for every 1 T-score reduction in BMD. CONCLUSIONS: Risk of clinical fragility fracture increases with decreasing BMD measurement parameters and anthropometric indicators in native China, and fracture HR varies from gender and site.

A VASt-domain protein regulates autophagy, membrane tension, and sterol homeostasis in rice blast fungus.

Sterols are a class of lipids critical for fundamental biological processes and membrane dynamics. These molecules are synthesized in the endoplasmic reticulum (ER) and are transported bi-directionally between the ER and plasma membrane (PM). However, the trafficking mechanism of sterols and their relationship with macroautophagy/autophagy are still poorly understood in the rice blast fungus Magnaporthe oryzae. Here, we identified the VAD1 Analog of StAR-related lipid transfer (VASt) domain-containing protein MoVast1 via co-immunoprecipitation in M. oryzae. Loss of MoVAST1 resulted in conidial defects, impaired appressorium development, and reduced pathogenicity. The MoTor (target of rapamycin in M. oryzae) activity is inhibited because MoVast1 deletion leads to high levels of sterol accumulation in the PM. Site-directed mutagenesis showed that the 902 T site is essential for localization and function of MoVast1. Through filipin or Flipper-TR staining, autophagic flux detection, MoAtg8 lipidation, and drug sensitivity assays, we uncovered that MoVast1 acts as a novel autophagy inhibition factor that monitors tension in the PM by regulating the sterol content, which in turn modulates the activity of MoTor. Lipidomics and transcriptomics analyses further confirmed that MoVast1 is an important regulator of lipid metabolism and the autophagy pathway. Our results revealed and characterized a novel sterol transfer protein important for M. oryzae pathogenicity.Abbreviations: AmB: amphotericin B; ATMT: Agrobacterium tumefaciens-mediated transformation; CM: complete medium; dpi: days post-inoculation; ER: endoplasmic reticulum; Flipper-TR: fluorescent lipid tension reporter; GO: Gene ontology; hpi: hours post-inoculation; IH: invasive hyphae; KEGG: kyoto encyclopedia of genes and genomes; MoTor: target of rapamycin in Magnaporthe oryzae; PalmC: palmitoylcarnitine; PM: plasma membrane; SD-N: synthetic defined medium without amino acids and ammonium sulfate; TOR: target of rapamycin; VASt: VAD1 Analog of StAR-related lipid transfer; YFP, yellow fluorescent protein.

Gender differences in a reference database of age-related femoral neck geometric parameters for Chinese population and their association with femoral neck fractures.

Femoral neck geometric parameters (FNGPs) are closely related to the strength of the femoral neck and the risk of fragility fractures. No reference database is available for FNGPs for Chinese population, and gender-related differences in FNGPs as well as their association with the risk of femoral neck fractures are unknown. This investigation aimed to set up reference databases for FNGPs, understand gender-related differences in FNGPs, and examine the association between FNGPs and the risk of osteoporotic fractures of the femoral neck. This study included 5268 females and 2156 males (aged 15-91years) from Chinese population. A total of 384 patients (282 females and 102 males) had sustained femoral neck fractures; 384 age- and sex-matched individuals without any fractures served as controls. Femoral neck DXA images were used to measure bone mineral density (BMD) and eight FNGPs. Our results showed that the age-related trends of FNGPs were fitted with the best goodness-of-fit by applying the cubic regression model. The trends shown by FNGPs were significantly different between male and female subjects, and the fitting curves were significantly higher in male subjects. After adjustments were made for age, height, weight, and body mass index, Cox regression analysis showed that changes in all FNGPs were related to increased hazard ratios (HRs) of femoral neck fractures. After further adjustment was made for BMD of the femoral neck, the HRs related to a cortical thickness (CT) decrease and buckling ratio (BR) increase in females went up by 3.35-folds (95% CI: 2.75-4.07) and 1.86-folds (95% CI: 1.33-2.60), respectively. In males, the HRs related to the decrease in CT and cross-sectional area (CSA) increased by 3.21-folds (95% CI: 2.32-4.45) and 1.88-folds (95% CI: 1.03-3.44), respectively. In conclusions, the reference databases of FNGPs established in this study will assist in the evaluation and prediction of femoral neck fracture risk in the clinic. The decrease in CT and increase in BR of the femoral neck were independent risk factors for osteoporotic fractures of the femoral neck in females from mainland China, while a decrease in CT and CSA were risk factors in male.

Epidemiology and management of osteoporosis in the People's Republic of China: current perspectives.

With the progressive aging of the population, osteoporosis has gradually grown into a global health problem for men and women aged 50 years and older because of its consequences in terms of disabilities and fragility fractures. This is especially true in the People's Republic of China, which has the largest population and an increasing proportion of elderly people, as osteoporosis has become a serious challenge to the Chinese government, society, and family. Apart from the fact that all osteoporotic fractures can increase the patient's morbidity, they can also result in fractures of the hip and vertebrae, which are associated with a significantly higher mortality. The cost of osteoporotic fractures, moreover, is a heavy burden on families, society, and even the country, which is likely to increase in the future due, in part, to the improvement in average life expectancy. Therefore, understanding the epidemiology of osteoporosis is essential and is significant for developing strategies to help reduce this problem. In this review, we will summarize the epidemiology of osteoporosis in the People's Republic of China, including the epidemiology of osteoporotic fractures, focusing on preventive methods and the management of osteoporosis, which consist of basic measures and pharmacological treatments.

Age-related bone turnover markers and osteoporotic risk in native Chinese women.

BACKGROUND: The rate of bone turnover is closely related to osteoporosis risk. We investigated the correlation between bone turnover markers and BMD at various skeletal sites in healthy native Chinese women, and to study the effect of changes in the levels of bone turnover markers on the risk of osteoporosis. METHODS: A cross-section study of 891 healthy Chinese women aged 20-80 years was conducted. The levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), serum cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. BMD at the posteroanterior spine and the hip was measured using DXA. RESULTS: Pearson's correlation coefficient found significant negative correlation between bone turnover marker and BMD T-score at different skeletal sites (r = -0.08 to -0.52, all P = 0.038-0.000). After adjustments for age and body mass index, the partial correlation coefficients between the OC, BAP, sNTX, sCTX and uCTX, and the T-scores at various skeletal sites were still significant. After adjustment of height and weight, the correlation coefficients between most BTMs and PA lumbar spine BMD were also significant. Multiple linear regression analysis showed that bone turnover markers were negative determinants of T-scores. BAP and OC accounted for 33.1% and 7.8% of the variations in the T-scores of the PA spine, respectively. Serum OC, BAP, uDPD, and sNTX accounted for 0.4-21.9% of the variations in the femoral neck and total hip T-scores. The bone turnover marker levels were grouped as per quartile intervals, and the T-scores, osteoporosis prevalence and risk were found to markedly and increase with increase in bone turnover marker levels. CONCLUSIONS: This study clarified the relationship between bone turnover markers and osteoporosis risk in native Chinese women. Bone turnover marker levels were found to be important determinants of BMD T-scores. Furthermore, osteoporotic risk significantly increased with increase in the levels of bone turnover markers.

Relationships between age-related biochemical markers of bone turnover and OPG, TGF-ß1 and TGF-ß2 in native Chinese women.

Osteoprotegerin (OPG), transforming growth factor-ß1 (TGF-ß1) and TGF-ß2 are cytokines closely associated with bone metabolism. However, their association with bone turnover markers in native Chinese women remains unknown. The study aims to investigate the relationship between bone metabolism related cytokines including OPG, TGF-ß1, TGF-ß2 and bone turnover markers in native Chinese women. The cross-sectional study was conducted on 691 healthy Chinese women (20-80 years old). Levels of OPG, TGF-ß1, TGF-ß2, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. The present study showed that OPG and TGF-ß2 had positive correlation with BAP, OC, uNTX, uCTX and uDPD, while TGF-ß1 showed negative correlation with BAP, OC, sCTX, uNTX and uCTX, and most of the coefficients of partial correlation remained significant after adjustments for age and body mass index (BMI). Multiple linear regression stepwise analysis showed that OPG and TGF-ß2 were positive determinative factors for BAP, sCTX, uNTX and uCTX, which could explain 0.6-16.6% of the variation in these markers. TGF-ß1 was a negative determinative factor for BAP, OC, sCTX and uCTX, which could explain 0.7-7.3% of the variation in these markers. This study suggested that measuring bone turnover indicators and serum cytokines simultaneously might help evaluating changes in bone turnover rate caused by aging or menopause in women.

[Relationship of age-related levels of serum sex hormones with bone mineral density decreasing rate in women].

OBJECTIVE: To explore the relationship between the changes of estrogen, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and bone mineral density (BMD) decreasing rate (BDR) at different skeletal regions and examine the effects of hormones levels on BDR. METHODS: An age cross-sectional study was conducted in 694 healthy adult women excluded from diseases and drugs affecting bone metabolism. Their age range was 20-80 years. The serum concentrations of FSH, LH and estradiol (E2) were measured with radioimmunoassay. And BDR was measured with a DXA fan-beam bone densitometer at various skeletal regions including lumbar spine, left hip and left forearm. RESULTS: The serum levels of FSH (r = -0.597 to -0.479, all P < 0.01) and LH r = -0.452 to -0.283, all P < 0.01) were significantly negatively correlated with BDR at various skeletal regions. Meanwhile, the serum level of E2 only had slightly positive correlation with hip and distal forearm (r = 0.077 to 0.122, all P < 0.05). After adjusting age and body mass index (BMI), serum FSH still had markedly negative correlation with BDR at various skeletal regions. However, the correlation coefficients became weak. Multiple line regression stepwise analysis revealed that serum FSH was a negative determinant factor of BDR at various skeletal regions: 20%-32% changes in BDR of various skeletal regions were determined by FSH, while LH only produced very small negative effects (0.6%-0.8%) on BDR of lumbar spine. Serum E2 seemed to be a positive determinant factor of skeletal regions and 2.5%-5.4% changes in BDR were determined by E2. The effects of serum FSH on BDR were approximately 3.8-12.8 folds than those of serum E2. CONCLUSIONS: BDR is correlated with increased FSH in women. The most critical factor for aging-related BDR is FSH in women while a decreased level of estrogen may be secondary.

Relationship between Serum Levels of OPG and TGF- ß with Decreasing Rate of BMD in Native Chinese Women.

The objective of this study was to investigate the relationship between serum levels of OPG, TGF- ß 1, and TGF- ß 2 and BMD decrease rate (BDR) in native Chinese women. This cross-sectional study was performed on 465 healthy native Chinese women aged 35-80 years. Serum levels of OPG, TGF- ß 1, and TGF- ß 2 were determined. BDR was measured by DXA at the posteroanterior spine, hip, and distal forearm. At all skeletal sites tested, there was a negative correlation between BDR and serum levels of both OPG (r = -0.122 to -0.230, all P = 0.007-0.000) and TGF- ß 2 (r = -0.100 to -0.173, all P = 0.029-0.000) and a positive correlation between BDR and serum TGF- ß 1 (r = 0.245 - 0.365, all P = 0.000). After adjustment for age and BMI, there were no statistically significant correlations between serum levels of OPG or TGF- ß 2 and BDR. However, statistically significant correlations between serum TGF- ß 1 and BDR at the lumbar spine and ultradistal forearm remained. Multiple linear regression stepwise analysis showed that serum OPG could explain 1.4-3.7% of BDR variation. Serum TGF- ß 1 was a positive determinant of BDR and could explain 5.3-13.3% of BDR variation.

Early bone mineral density decrease is associated with FSH and LH, not estrogen.

BACKGROUND: It remains unclear whether gonadotropins or estrogen is responsible for early bone mineral density (BMD) decrease in Chinese women. METHODS: A cross-sectional study was conducted on 368 healthy adult women, aged 35-60 years. We measured BMD, calculated BMD decrease rates (BDRs) and assessed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E(2)) levels. RESULTS: BDR was significantly negatively correlated with serum FSH (r=-0.429 to -0.622, all p=0.000) and LH (r=-0.359 to -0.526, all p=0.000). After adjustment for age and body mass index, the negative correlations of serum FSH and LH with BDR persisted, but there was no overall correlation between serum E(2) and BDR. Multiple linear stepwise regression analysis suggested that serum FSH is a negative determinant of BDR. Serum E(2) seems to be a positive determinant of BDR in a few parts of the skeleton. CONCLUSIONS: The decrease of BMD during the menopause is associated with FSH and LH levels, rather than E(2) in Chinese women.

The relationship between bone turnover markers and BMD decreasing rates in Chinese middle-aged women.

BACKGROUND: The relationship between bone turnover markers (BTMs) and BMD decreasing rate (BDR) in Chinese women is unclear. Wu investigated the relationship between (BTMs) and BDR at various skeletal sites in Chinese middle-aged women. METHODS: A cross-section study of 555 healthy Chinese women over 35-60years of age. BMD at posteroanterior spine, the left hip, and the left forearm were measured with a DXA. Levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), cross-linked N-terminal telopeptides of type I collagen (sNTX) and total urinary deoxypyridinoline (uDPD) were determined. RESULTS: BDR at various skeletal sites had significant negative correlation with serum OC(r=-0.395 to -0.530), BAP(r=-0.297 to -0.486), and sNTX(r=-0.207 to -0.272). After adjustment of age and weight, serum OC, BAP, and sNTX rather than total uDPD still exhibited significant correlations with BDR. Stepwise regression analyses showed that, serum OC and BAP were the significantly negative determinants of BDR. Between 4.7-27.7% and 1.2-16.1% of the changes in BDR were determined by serum OC and BAP, respectively. However, sNTX and total uDPD had no significant effect on BDR at various skeletal sites. CONCLUSIONS: This study indicated the correlation between BTMs and early-stage BDR in Chinese middle-aged women and suggested that serum OC and BAP, rather than sNTX and total uDPD, are the key determining factors of early BMD decreases.

The relationship between the levels of gonadotropic hormones and OPG, leptin, TGF-beta1 and TGF-beta2 in Chinese adult women.

BACKGROUND: The relationship between the levels of gonadotropic hormones and bone metabolism-related cytokines in Chinese women is unclear. We investigated the relationship between FSH and LH and OPG, leptin, TGF-beta1, and TGF-beta2 in Chinese women. METHODS: A cross-sectional study of 694 Chinese women, aged 20 to 82y was conducted. Levels of serum FSH, LH, OPG, leptin, TGF-beta1, and TGF-beta2 were determined. RESULTS: In premenopausal females, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels seemly showed no correlation with the cytokine levels. In perimenopausal females, serum FSH and LH levels showed significant positive correlation with osteoprotegerin (OPG) and transforming growth factor-beta2 (TGF-beta2) levels (r=0.286 to 0.405, all P=0.000), whereas they showed negative correlation with TGF-beta1 levels (r=-0.413 and -0.354, all P=0.000). In postmenopausal females, FSH and LH levels showed positive correlation with OPG levels (r=0.247 and 0.241, all P=0.000), negative correlation with leptin and TGF-beta1 levels (r=-0.234 to -0.319, all P=0.000), and no correlation with TGF-beta2 levels. Multiple linear regression stepwise analysis revealed the following results. In premenopausal females, 2.0% and 1.5% of the changes in LH could be explained by OPG and leptin, respectively, while 1.9% of the changes in OPG could be explained by LH. In perimenopausal females, the determinants of OPG and TGF-beta1 on FSH were 10.9% and 17.0%, respectively, and the determinants of OPG, TGF-beta1 and TGF-beta2 on LH were 4.5%, 4.9% and 16.4%, respectively. The determinants of FSH and LH on OPG were 14.5% and 2.5%, respectively. The determinant of FSH on TGF-beta1 was 4.5%, while the determinant of LH on TGF-beta2 was 16.4%. In postmenopausal females, the determinants of leptin and OPG on FSH were 10.2% and 2.8%, respectively, and the determinants of OPG and TGF-beta1 on LH were 5.8% and 2.3%, respectively. The determinant of FSH on OPG, leptin and TGF-beta1 were 6.1%, 3.4% and 9.2%. CONCLUSIONS: These results indicate that age-related gonadotropic hormone levels are associated with changes in OPG, TGF-beta1, TGF-beta2 and leptin, and change with menopausal status.

Suppressive effect of dexamethasone on TIMP-1 production involves murine osteoblastic MC3T3-E1 cell apoptosis.

High dose glucocorticoid (GC) treatment induces osteoporosis partly via increasing osteoblast apoptosis. However, the mechanism of GC-induced apoptosis has not been fully elucidated. Osteoblast-derived tissue inhibitor of metalloproteinase-1 (TIMP-1) was recently reported to be involved in bone metabolism. Our previous study demonstrated that TIMP-1 suppressed apoptosis of the mouse bone marrow stromal cell line MBA-1 (pre-osteoblast) induced by serum deprivation. Therefore, we tested the effect of the GC dexamethasone (Dex) on TIMP-1 production in murine osteoblastic MC3T3-E1 cells and further determined whether this action is associated with Dex-induced osteoblast apoptosis. Dex decreased TIMP-1 production in MC3T3-E1 cells, and this effect was blocked by the glucocorticoid receptor (GR) antagonists, RU486 and RU40555. Recombinant TIMP-1 protein reduced caspase-3 activation and apoptosis induced by Dex in MC3T3-E1 cells. In addition, the pro-apoptotic effect of the Dex was augmented by suppression of TIMP-1 with siRNA. Furthermore, mutant TIMP-1, which has no inhibitory effects on MMPs, yet protects MC3T3-E1 cells against Dex-induced apoptosis. Our study demonstrates that Dex suppresses TIMP-1 production in osteoblasts through GR, and this effect is associated with its induction of osteoblast apoptosis. The anti-apoptotic action of TIMP-1 is independent of its inhibitory effects on MMPs activities. The decrease in TIMP-1 production caused by Dex may contribute to the mechanisms of Dex-induced bone loss.

Relationship between age-related serum concentrations of TGF-beta1 and TGF-beta2 and those of osteoprotegerin and leptin in native Chinese women.

BACKGROUND: Transforming growth factor-beta 1 (TGF-beta1), TGF-beta2, osteoprotegerin (OPG), and leptin are important cytokines in the regulation of bone remodeling. We investigated the relationship of TGF-beta1 and TGF-beta2 concentrations with those of OPG and leptin in Chinese females. METHODS: The serum concentrations of TGF-beta1, TGF-beta2, OPG, and leptin were measured by ELISA in 459 healthy Chinese females aged 25-80 y. RESULTS: The mean values (+/-SD) of the serum concentrations of TGF-beta1, TGF-beta2, OPG, and leptin in Chinese females were 29.7+/-1.69 microg/l, 13.7+/-3.86 microg/l, 3.81+/-1.96 pmol/l, and 10.5+/-2.01 microg/l, respectively. Further, the serum TGF-beta1 concentrations of postmenopausal women were significantly lower than those of perimenopausal and premenopausal women (24.3+/-1.59 vs 33.4+/-1.69 and 37.6+/-1.64, respectively), while the TGF-beta2 concentrations of postmenopausal women were significantly higher than those of perimenopausal and premenopausal women (14.6+/-3.91 vs 13.5+/-3.93 and 11.7+/-2.68, respectively). The serum TGF-beta1 concentration was found to be significantly negatively correlated with age (r=-0.335, P=0.000) and the TGF-beta2 concentration, to be significantly positively correlated with age (r=0.230, P=0.000). The TGF-beta1 concentration was found to be significantly negatively correlated with both TGF-beta2 (r=-0.261, P=0.000) and OPG (r=-0.313, P=0.000) concentrations; a significantly positive correlation was found between the TGF-beta1 and leptin concentrations (r=0.164, P=0.000) and between TGF-beta2 and OPG concentrations (r=0.432, P=0.000). CONCLUSION: These results provide age-related reference values of TGF-beta1 and TGF-beta2 in Chinese adult women, and reveal the relationships between these cytokines.

Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women.

BACKGROUND: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may play an important role in bone mass regulation in postmenopausal women. METHODS: A cross-sectional study of 699 healthy Chinese women, aged 20 to 82 y, was conducted. Serum FSH and LH and BMD were measured at the posteroanterior (PA) spine, lateral spine, total hip, and distal forearm. RESULTS: The geometric mean values (+/-SD) of serum FSH and LH in premenopausal women were 3.94 +/- 2.08 and 7.51 +/- 2.58 IU/l, respectively, and in postmenopausal women were 28.8 +/- 1.88 and 25.6 +/- 1.95 IU/l, respectively. The correlation of FSH to BMD at different skeletal regions (r = -0.597 - -0.492, P = 0.000) was higher than that of LH to BMD (r = -0.452 - -0.332, P = 0.000). The prevalences of osteoporosis for the quartiles of FSH at various skeletal sites were 0.57%, 0.43%, 27.1%, and 30.9%, respectively; and of LH were 2.14%, 4.43%, 19.5%, and 26.0%, respectively. The prevalence of osteoporosis in 3rd and 4th quartile was more significantly increased than the 1st and 2nd quartile. CONCLUSIONS: These data suggest that FSH and LH levels in circulation are associated with BMD changes and osteoporosis occurrence in Chinese women.