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.

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.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Elevated triglycerides rather than other lipid parameters are associated with increased urinary albumin to creatinine ratio in the general population of China: a report from the REACTION study.

BACKGROUND: Dyslipidaemia has always been regarded as the cornerstone of arteriosclerosis and is related to the pathogenesis of renal insufficiency. However, it is unclear which routinely available lipid parameter is related to urinary albumin to creatinine ratio (UACR). The purpose of this study was to examine the lipid abnormalities associated with UACR in the general population in China. METHODS: The present study was nested in an ongoing Risk Evaluation of cAncers in Chinese diabetic Individuals: A lONgitudinal (REACTION) study, which was designed to demonstrate the association of abnormal glucose metabolism with the risk of cancer in the Chinese population. This cross-sectional study included 34, 569 subjects (11, 390 males and 23, 179 females) from 8 different regional community cohorts, with an average age of 57.9 years. The UACR data were divided into the < 25% group, the 25-49% group, the 50-74% group, and the ≥ 75% group according to the quartile division of the centre where the subjects visited. The lipid classes were defined according to the guidelines for the prevention and treatment of dyslipidaemia in Chinese adults. Multiple logistic regression analysis was used to evaluate the association of the lipid parameters and UACR. RESULTS: Multivariable regression analysis revealed that compared with the other lipid parameters, triglycerides (TG) showed an adjusted odds ratio that was significant in model 1-4. This relationship was attenuated after adjusting for Haemoglobin A1c (HbA1c) and blood pressure (BP), but TG ≥ 2.3 mmol/L was still significantly associated with UACR in total subjects and in both men and women (OR: 1.131, 95% CI 1.065-1.203, P < 0.001 in total subjects; OR: 1.134, 95% CI 1.022-1.258, P = 0.017 in men; OR: 1.129, 95% CI 1.046-1.219, P = 0.002 in women). In the stratified analysis, elevated TG was significantly associated with increased urinary albumin in subjects with eGFR ≥ 90 mL/min per 1.73 m2, 5.6 ≤ FBG < 7.0 or 7.8 ≤ PBG < 11.1 mmol/L, 24 ≤ BMI < 28 kg/m2, 120 ≤ SBP < 140 and/or 80 ≤ DBP < 90 mmHg. CONCLUSIONS: We conclude that high TG levels rather than total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol levels are associated with UACR in the general population in China.

Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity.

Resveratrol (3,5,4-trihydroxystilbene, RES), a natural antioxidant, prevents bone loss by attenuating damage caused by oxidative stress. Our previous research revealed that the forkhead box O1 (FoxO1)/ß-catenin signaling pathway affected the proliferation and differentiation of osteoblasts through its regulation of redox balance, and RES regulated the expression of FoxO1 to control white adipose tissue and then ameliorate an overweight condition. Based on previous research, we hypothesized that RES regulates FoxO1 transcriptional activity through the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway to achieve an antioxidative effect on osteoporosis and then we confirmed this hypothesis in the present study. An ovariectomized (OVX) rat model of osteoporosis and a H2O2­induced oxidative cell injury model in RAW 264.7 cells were established to explore the underlying molecular mechanisms of how RES confers an antioxidant effect and prevents bone loss. The obtained results demonstrated that RES strongly prevented bone loss induced by oxidative stress in vivo. More specifically, RES effectively decreased the receptor activator of nuclear factor-κB ligand (RANKL) together with the tartrate-resistant acid phosphatase­5b (TRAP­5b) level, but elevated the osteoproprotegrin (OPG) level and attenuated bone microarchitecture damage. Notably, RES, due to its antioxidant effect, suppressed RANKL production and then inhibited osteoclastogenesis in the OVX rats. In vitro, RES improved the oxidative stress status of cells and thus inhibited the mRNA expression of osteoclast-specific enzymes. These data indicate that RES has a significant bone protective effect by antagonizing oxidative stress to suppress osteoclast activity, function and formation both in vivo and in vitro. Moreover, at the molecular level, we confirmed, for the first time, that RES upregulated FoxO1 transcriptional activity by inhibiting the PI3K/AKT signaling pathway, and hence promoted resistance to oxidative damage and restrained osteoclastogenesis. Inhibition of the PI3K/AKT signaling pathway may be induced by RANKL. FoxO1 is a major action target of RES to confer anti-osteoporosis function, and whose effect stems from its power to improve redox balance.

Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus. METHODS: This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level. RESULTS: In patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37-4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47-38.03), dyslipidemia (OR 2.65, CI 1.54-4.56), diastolic blood pressure (OR 1.02, CI 1.00-1.04), and body mass index (OR 0.95, CI 0.92-0.99) are independent factors for early-onset T2DM. CONCLUSIONS: We observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.

The proliferation, differentiation, and mineralization effects of puerarin on osteoblasts in vitro.

AIM: Osteoblasts are key functional cells in the process of bone metabolic balance. Phytoestrogens have an important influence on the proliferation and differentiation of osteoblasts. Puerarin, a plant estrogen, has a wide range concentration in vitro on the function of osteoblasts. The current study investigates the effect of the phytoestrogen puerarin on the proliferation, differentiation, and mineralization of osteoblasts in vitro. METHODS: The calvaria bone of eight-ten Wistar rats which were born within 24 h were obtained in aseptic condition. After enzyme digestion, isolation, purified osteoblasts of rats were cultured for further study. The cells of the first to third generation were divided into a control group and a puerarin-treated group with 10(-3)-10(-10) mol·L(-1) puerarin. The cells were exposed to the medium containing a low level of carbohydrates, 10% (V/V) FBS for 24 h. After 1 to 4 days of culture, the OD values on the proliferation of osteoblasts in each group were determined by microplate reader. The cells were cultured in the medium containing 50 µg·mL(-1) vitamin C, 10(-2) mol·L(-1) sodium glycerophosphate, 10% FBS and the medium was changed every 3 to 4 days. After 2 to 8 days of culture, expression of alkaline phosphatase were tested and compared by microplate reader. The mineral nodes of osteoblasts were dyed using alizarin red or improved Von Kossa way after four weeks. RESULTS: Compared with those in the 10(-5)-10(-9) mol·L(-1) puerarin, the proliferation of osteoblasts, the expression of alkaline phosphatase, and the number of mineral nodes of osteoblasts were significantly decreased in the control group. The increase was the fastest in the third day, while on the fourth day it was decreased, and arrived at statistical significance compared with the alkaline phosphatase activities and control group. The 10(-6) mol·L(-1) group was the most distinct, and formed the most mineralized nodule. Compared with the 10(-3) mol·L(-1) puerarin group, those changes were markedly increased in the control group. CONCLUSIONS: Puerarin has proliferation, differentiation, and mineralization effects on osteoblasts in a dose-dependent manner, and has a double-way effect on the osteoblasts in vitro. A low-dose showed positive effects on the development of osteoblasts, and high-dose puerarin could inhibit the formation of bone.

Effect of glucocorticoid-induced oxidative stress on the expression of Cbfa1.

Glucocorticoids therapy is strongly limited since extended glucocorticoids can cause serious side effects, including increased susceptibility to develop the bone disease osteoporosis. Despite its side effects recognized importance to clinicians, seldom is known about how glucocorticoids directly impact bone-forming osteoblasts. Previous studies showed that dexamethasone (DEX) induces excessive production of reactive oxygen species (ROS), and causes oxidative stress in rat hippocampal slice cultures. To assess the implications and investigate the mechanisms of glucocorticoid-elicited osteoporosis, we hypothesize that DEX exposure induces oxidative stress which leads to decreased Cbfa1 mRNA expression, and predict that the antioxidant N-acetylcysteine (NAC) mitigates the damaging effects of DEX. Oxidative stress is implicated in osteoporosis. Furthermore, the osteoblast transcriptional factor Cbfa1 is reported to play a protective role against osteoporosis in postmenopausal women. Cells treated with (0.1, 1, 10µM) DEX exhibited signs of oxidative damages including depletion in total antioxidant capacity (T-AOC), increased ROS formation, and enhanced lipid peroxidation. Cbfa1 mRNA expression, by RT-PCR, was significantly reduced after exposure to (0.1, 1, 10µM) DEX. Pretreatment with the antioxidant NAC (2mM) prevented DEX-induced decrease in Cbfa1 mRNA. This study provides insight into the underlying mechanisms of high dose DEX-induced osteotoxicity. DEX (0.1, 1, 10µM) decreases the expression of Cbfa1 mRNA and inhibits differentiation and function of osteoblasts by inducing oxidative stress. The antioxidant NAC can mitigate the oxidative stress damaging effects of DEX. In addition, this study distinguishes itself by identifying Cbfa1 as a target for high dose DEX-induced osteotoxicity.

[A Meta-analysis of alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis].

OBJECTIVE: To assess the efficiency and safety of alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). METHODS: The electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, Chinese BioMedical Literature Database (CBM) and Wanfang Data were searched for all randomized controlled trials (RCT) of alendronate vs. placebo. Two reviewers independently selected trials for inclusion, assessed trial quality using Jadad's scale and extracted the data. RevMan 5.1 software was used for data synthesis and Meta-analysis. RESULTS: Seven studies with 1111 patients were included. Compared with placebo, alendronate significantly increased bone mineral density (BMD) at the lumbar spine[MD = 3.35, 95%CI (2.67-4.02), P = 0.000] and the femoral neck[MD = 1.90, 95%CI (0.89-2.92), P = 0.000] after 12 months of therapy. After 24 months of therapy, alendronate significantly increased BMD at the lumbar spine[MD = 3.91, 95%CI (2.37-5.45), P = 0.000], but not at the femoral neck[MD = 1.91, 95%CI (-1.15-5.02), P = 0.22]. Compared with placebo, no significant reduction was found by the use of alendronate in the incidence of vertebral fractures [RR = 1.00, 95%CI (0.49-2.07), P = 0.99] or nonvertebral fractures [RR = 1.02, 95%CI (0.49-2.14), P = 0.95]. No difference was shown with the adverse event between the two groups[RR = 0.97, 95%CI (0.90-1.05), P = 0.47]. CONCLUSIONS: Alendronate is effective for the prevention and treatment of glucocorticoid-induced bone loss at the lumbar spine and the femoral neck with relatively good safety profile. Yet, there is no significant difference between the two groups in reducing the incidence of vertebral fractures and non-vertebral fractures. Large-scale RCT designed to observe whether different lengths of alendronate therapy will influence the efficiency should be conducted in the future and to further explore whether it can reduce the incidence of fractures.

Dynamic oxidative stress and DNA damage induced by oestrogen deficiency and protective effects of puerarin and 17ß-oestradiol in ovariectomized rats.

Oxidative stress plays an essential role in the pathogenesis of cardiovascular diseases and osteoporosis resulting from oestrogen deficiency in the postmenopausal period. In this report, we observed a dynamic change of oxidative stress and DNA damage after ovariectomy in female rats. We then compared phytoestrogen puerarin and 17ß-oestradiol (E2) in their effects on oestrogen deficiency-induced oxidative stress and DNA damage. Serum total antioxidant capacity (TAC), malondialdehyde (MDA) and lymphocytes DNA damage (comet%) were measured. There was a gradual increase in oxidative stress in the ovariectomized (OVX) rats over time after ovariectomy, as compared to rats receiving sham operation. OVX rats that were on puerarin and E2 showed increased TAC and decreased MDA in the serum, as well as decreased lymphocytes comet%. Puerarin appeared to have a more powerful protective effect on DNA oxidative damage than E2. The study indicates that postmenopausal women may benefit from phytoestrogen puerarin.

Oxidative stress in Graves' disease patients and antioxidant protection against lymphocytes DNA damage in vitro.

DNA damage to peripheral blood lymphocytes of patients with Graves' disease (GD) was studied in vitro before and after treatment with antioxidants, melatonin, quercetin, N-acetylcysteine (NAC) and vitamin C. DNA damage (comet %) was remarkably higher in patients (23.7 +/- 5.5%) than that in healthy persons (9.8 +/- 3.2%, p < 0.01). Plasma malondialdehyde (MDA) content (7.90 +/- 1.77 microM) of patients was significantly higher than that of healthy persons (4.71 +/- 1.19 microM, p < 0.01). Also, the plasma total antioxidant capacity (TAC) (7.53 +/- 1.35 U/ml) in GD patients was significantly lower than that in healthy persons (10.56 +/- 2.21 U/ml, p < 0.01). Negative correlations were observed between plasma TAC and DNA damage in lymphocytes (r = -0.599, p < 0.01), and between plasma TAC and MDA (r = -0.40, p < 0.05) in GD patients. After treatment with 100 microM melatonin, quercetin or NAC for 4 h in vitro, DNA damage in lymphocytes in GD patients declined significantly (from 23.8 +/- 4.4% to 14.4 +/- 4.0%, p < 0.001 for melatonin, from 23.4 +/- 4.7% to 18.1 +/- 4.3%, p < 0.01 for quercetin, from 23.7 +/- 4.0% to 18.7 +/- 5.7%, p < 0.05 for NAC), while there was little change with concentrations of 1-100 microM of vitamin C. However, 1000 microM vitamin C enhanced DNA damage significantly (from 23.8 +/- 2.3% to 30.3 +/- 3.9%, p < 0.05). Our results showed that oxidative stress existed in GD patients and the antioxidants melatonin, quercetin and NAC are beneficial for DNA damage in lymphocytes of GD patients in vitro.