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.

The BRAFV600E mutation maintains the aggressiveness of papillary thyroid cancers requiring downregulation of primary cilia.

Although disorders of primary cilia (PCs) were first reported in human papillary thyroid cancer (PTC) tissues in 1987, their precise role in PTC remains unclear. PCs sense the thyroid follicle colloid environment and act as a cell signaling hub. The present study investigated whether PCs are needed for BRAFV600E-driven PTC. We assessed whether BRAFV600E protein expression correlates with papillary histological architecture and clinicopathological features of PTC. We found that expression of ciliary intraflagellar transport 88 (IFT88) and PC formation were reduced in BRAFV600E-driven PTCs and that loss of cilia may be associated with lymph node metastasis. In PTC cells, the BRAFV600E mutation maintained the aggressiveness of PTC, which was partially related to loss of PCs. Our work confirms that BRAFV600E mutation-driven PC downregulation contributes to maintaining the aggressiveness of PTCs and that manipulating PC can potentially reduce the adverse incidence of PTC in a range of conditions.

Codonopsis pilosula polysaccharides promote osteogenic differentiation and inhibit lipogenic differentiation of rat bone marrow stem cells by activating ß-catenin.

Aberrant bone marrow mesenchymal stem cell (BMSC) lineage differentiation leads to osteoporosis. Codonopsis pilosula polysaccharides (CPPs) have been widely used in traditional Chinese medicines, due to their multiple pharmacological actions. However, little is known regarding their effects on BMSC differentiation. This study aimed to identify the effects and mechanisms of CPPs on osteogenic and adipogenic differentiation in rat BMSCs. An osteoporosis model was established in Sprague-Dawley (SD) rats through bilateral ovariectomy (OVX), and be applied to observe the effect of CPPs on osteoporosis in vivo. The ability of CPPs to affect rBMSC proliferation was determined using the CCK-8 assay, and the osteogenic differentiation of rBMSCs measured by ALP and Alizarin Red S staining. The adipogenic differentiation of rBMSCs was measured by Oil Red O staining. The mRNA and protein levels related to osteogenesis and adipogenic differentiation of rBMSCs were measured using qRT-PCR and western blotting, respectively. Cellular immunofluorescence was used to detect cytokine expression and localisation in rBMSCs. We observed that CPPs ameliorated bone loss in OVX rats. CPPs considerably enhanced osteogenic differentiation by increasing ALP activity and the prevalence of mineralised nodules and promoting the mRNA and protein expression of osteogenic differentiation markers (RUNX2, COL I, ALP, and OPN). Furthermore, it inhibited the accumulation of lipid vesicles in the cytoplasm and the mRNA and protein expression levels of adipogenic differentiation markers (PPARγ and C/EBPα) in a concentration-dependent manner. Meanwhile, CPPs notably increased the mRNA and protein expression of ß-catenin, the core protein of the Wnt/ß-catenin signaling pathway, in a concentration-dependent manner. Adding DKK1, a mature inhibitor of the Wnt/ß-catenin signaling pathway, partially suppressed CPP-stimulated ß-catenin activation, and reversed the acceleration of osteogenic differentiation and the inhibition of lipogenic differentiation. Our observations demonstrated CPPs ameliorate bone loss in OVX rats in vivo, and favour osteogenic differentiation while inhibit adipogenic differentiation of rBMSCs in vitro. The findings suggested that CPPs could serve as functional foods for bone health, and have great potential for the prevention and treatment of osteoporosis.

Thioredoxin-interacting protein: A new therapeutic target in bone metabolism disorders?

Target identification is essential for developing novel therapeutic strategies in diseases. Thioredoxin-interacting protein (TXNIP), also known as thioredoxin-binding protein-2, is a member of the α-arrestin protein family and is regulated by several cellular stress factors. TXNIP overexpression coupled with thioredoxin inhibits its antioxidant functions, thereby increasing oxidative stress. TXNIP is directly involved in inflammatory activation by interacting with Nod-like receptor protein 3 inflammasome. Bone metabolic disorders are associated with aging, oxidative stress, and inflammation. They are characterized by an imbalance between bone formation involving osteoblasts and bone resorption by osteoclasts, and by chondrocyte destruction. The role of TXNIP in bone metabolic diseases has been extensively investigated. Here, we discuss the roles of TXNIP in the regulatory mechanisms of transcription and protein levels and summarize its involvement in bone metabolic disorders such as osteoporosis, osteoarthritis, and rheumatoid arthritis. TXNIP is expressed in osteoblasts, osteoclasts, and chondrocytes and affects the differentiation and functioning of skeletal cells through both redox-dependent and -independent regulatory mechanisms. Therefore, TXNIP is a potential regulatory and functional factor in bone metabolism and a possible new target for the treatment of bone metabolism-related diseases.

Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management.

Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.

25-Hydroxyvitamin D and Incidence of Type 2 Diabetes from a Chinese Cohort Study.

This study aims to examine whether low serum 25-hydroxyvitamin D [25(OH)D] concentrations are correlated with increased risk of incident type 2 diabetes (T2D) in a Chinese population. The present prospective cohort study included 5,543 participants aged 40-75 y old and is free of diabetes at baseline in Lanzhou city, China. Serum 25(OH)D concentrations were measured. T2D incidence was defined based on obtained results from oral glucose tolerance tests or a self-reported previous diagnosis of diabetes by healthcare professionals. The association between baseline serum 25(OH)D concentrations and incident T2D was investigated using Cox proportional hazards model and restricted cubic spline. Of 5,543 participants (1,433 men and 4,110 women) followed for an average period of 3.9 y, 239 (4.3%) developed diabetes. No significant difference in serum 25(OH)D concentrations was found between individuals who developed diabetes and those who did not (p>0.05). Furthermore, serum 25(OH)D quartiles were not associated with T2D incidence (HR 1.33, 95% CI: 0.89-1.97, p=0.18) after adjusting for body mass index (BMI) and other potential confounders, as well as in subgroups classified with sex (men, women), glucose status (normal glucose tolerance, prediabetes), and BMI (<25 kg/m2, ≥25 kg/m2). The lower serum 25(OH)D concentrations are not associated to a higher risk of incident T2D in the present Chinese cohort after adjusting for BMI and other numerous potential confounding factors.

Metabolic (Dysfunction)-Associated Fatty Liver Disease in Chinese Patients with Type 2 Diabetes from a Subcenter of the National Metabolic Management Center.

BACKGROUND: Few studies have investigated the epidemiological metabolic (dysfunction) associated with fatty liver disease (MAFLD) in China, especially among those with type 2 diabetes. METHODS: We recruited 3553 patients aged 18-75 years with type 2 diabetes who underwent abdominal ultrasound and serum biochemical analyses. Patient information including demographic and anthropometric parameters was also collected. RESULTS: Overall, 63.2% of type 2 diabetic patients had MAFLD. Among the MAFLD patients, the proportions of lean, nonobese, and obese MAFLD were 23.1%, 75.7%, and 24.3%, respectively, and the percentage of previously undiagnosed MAFLD was 42.2%. MAFLD patients were younger, had shorter diabetic duration, and had greater BMI, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting insulin, postprandial insulin, total cholesterol, and insulin resistance levels (HOMA-IR and TyG index). Liver fibrosis diagnostic panels revealed that the proportions of elevated AST (≥40 U/L) and ALT (≥40 U/L) were 7.3% and 18.5%, respectively. The distributions of AST-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) index, and nonalcoholic fatty liver disease fibrosis score (NFS) per stage were as follows: APRI-low 55.1%, indeterminate 35.3%, and high 9.5%; FIB-4-low 48.2%, indeterminate 45.3%, and high 6.5%; and NFS-low 15.0%, indeterminate 70.0%, and high 13.0%. CONCLUSIONS: MAFLD is a very common condition and generally had greater frequency of metabolic characteristics among type 2 diabetics in China. Many MAFLD patients were in the "indeterminate" or "high" stage when APRI, FIB-4, and NFS were assessed. Assessment of MAFLD should be included in the management of type 2 diabetes.

Vitamin D deficiency in diabetes exacerbates longitudinal risk for atherosclerotic cardiovascular disease in Lanzhou, China.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency has been considered a risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate the correlation between serum 25(OH)D concentration and the risk of ASCVD in Chinese, especially in Type 2 diabetes mellitus (T2DM) patients. METHODS AND STUDY DESIGN: Based on the "REACTION" study conducted in 2011, some 9,014 Lanzhou residents aged 40-75 years were followed from 2014 to 2016. A total of 7,061 with complete data were analyzed. Baseline population was classified into four groups based on 25(OH)D quartiles. Cox proportional hazard models were used to estimate relations between 25(OH)D concentration and ASCVD. RESULTS: The prevalence of vitamin D deficiency [25(OH)D <20 ng/mL] was 75.1%. Followed-up for 3.3 years, those with the lowest of 25(OH)D concentration had higher rates of ASCVD (HR: 1.748, 95% CI: 1.149-2.660, p<0.01). A 10 ng/mL increase in baseline serum 25(OH)D was accompanied by a 24 % decrease in ASCVD risk (HR: 0.760, 95% CI: 0.590-0.980, p<0.05). For 25(OH)D and ASCVD risk with glycaemic status, low 25(OH)D plus T2DM was highly associated with ASCVD (HR: 2.296, 95% CI: 1.246-4.232, p<0.01). With diabetes, ASCVD risk decreased by 36% when serum 25(OH)D increased by 10 ng/mL (HR: 0.644, 95% CI: 0.440-0.941, p<0.05). CONCLUSIONS: Serum 25(OH)D is independently and inversely associated with the risk of ASCVD in Lanzhou Chinese, especially those with T2DM. Maintaining sufficient levels of vitamin D may be an effective measure in ASCVD prevention.

NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

Osteoporosis is a systemic bone metabolism disease that often causes complications, such as fractures, and increases the risk of death. The nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an intracellular multiprotein complex that regulates the maturation and secretion of Caspase-1 dependent proinflammatory cytokines interleukin (IL)-1ß and IL-18, mediates inflammation, and induces pyroptosis. The chronic inflammatory microenvironment induced by aging or estrogen deficiency activates the NLRP3 inflammasome, promotes inflammatory factor production, and enhances the inflammatory response. We summarize the related research and demonstrate that the NLRP3 inflammasome plays a vital role in the pathogenesis of osteoporosis by affecting the differentiation of osteoblasts and osteoclasts. IL-1ß and IL-18 can accelerate osteoclast differentiation by expanding inflammatory response, and can also inhibit the expression of osteogenic related proteins or transcription factors. In vivo and in vitro experiments showed that the overexpression of NLRP3 protein was closely related to aggravated bone resorption and osteogenesis deficiency. In addition, abnormal activation of NLRP3 inflammasome can not only produce inflammation, but also lead to pyroptosis and dysfunction of osteoblasts by upregulating the expression of Caspase-1 and gasdermin D (GSDMD). In conclusion, NLRP3 inflammasome overall not only accelerates bone resorption, but also inhibits bone formation, thus increasing the risk of osteoporosis. Thus, this review highlights the recent studies on the function of NLRP3 inflammasome in osteoporosis, provides information on new strategies for managing osteoporosis, and investigates the ideal therapeutic target to treat osteoporosis.

Correlation of serum vitamin D with lipid profiles in middle-aged and elderly Chinese individuals.

BACKGROUND AND OBJECTIVES: Deficiency of vitamin D has been associated with various health conditions. The purpose of this study was to evaluate the associations between the serum 25OHD concentration and lipid profiles in Chinese individuals. METHODS AND STUDY DESIGN: Serum 25OHD and lipid profiles were obtained for a cross sectional sample of 10100 individuals aged 40-75 years from Lanzhou city, which is located in western China. Linear-by-linear association, partial correlation analysis and multiple logistic regression analysis were used to evaluate associations between serum 25OHD concentration and lipid profiles. RESULTS: 10038 subjects aged 40- 75 years were included in the study. The 25OHD deficient and insufficient groups had higher TC, LDL-C and TG when compared to the optimal group. The dyslipidemia rates of vitamin D deficiency, insufficiency, and sufficiency groups were 45.4%, 41.6%, 38.8%, respectively. The prevalence rates of dyslipidemia, high cholesterol, high LDL-C, hypertriglyceridemia and mixed type hyperlipidemia exhibited decline trend in vitamin D deficiency, insufficiency and sufficiency groups. The correlation coefficients in between TC and 25OHD, LDL-C and 25OHD, TG and 25OHD were -0.033, -0.022, -0.044, respectively. Low 25OHD levels were associated with the risk of onset of dyslipidemia [OR 1.225 (95% CI 1.075-1.397), p=0.002] in the logistical regression analyses. CONCLUSIONS: Deficient serum 25OHD is associated with higher TC, LDL-C, and TG in middle-aged and elderly Chinese individuals. These findings suggest that low 25OHD levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease.

[Correlation of type 2 diabetes and impaired glucose regulation with chronic kidney disease in middle-aged and elderly individuals].

OBJECTIVE: To explore the correlation of different glucose metabolism statues with chronic kidney disease (CKD) in middle-aged and elderly individuals in Lanzhou. METHODS: Based on the baseline data of REACTION Study in Lanzhou area, we randomly sampled 10 038 residents aged 40-75 years in 3 communities in Lanzhou, who were classified into normal glucose tolerance (NGT), impaired glucose regulation (IGR) and diabetes groups. The estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) were used to assess the renal function and albuminuria, respectively. Binary logistic regression was performed to analyze the contribution of the risk factors to CKD. Polynominal regression was used to determine the trends of eGFR with the increment of ACR. RESULTS: Among all the participants, the prevalences of albuminuria, CKD and renal insufficiency (RI) were 26.2%, 27.4% and 2.5%, respectively. The prevalence of albuminuria, CKD and RI were significantly higher in the diabetes group than in IGR and NGT groups (P < 0.05). In IGR group, age, hypertension, and hypertriglyceridemia were positively correlated with the risk of RI (OR: 1.113, 1.904, and 2.608, respectively; P < 0.05). In diabetes group, age, coronary heart disease, obesity, hypertriglyceridemia, and elevated LDL-C level were positively correlated with the risk of RI (OR: 1.069, 2.535, 3.359, 1.827, and 2.690, respectively; P < 0.05). Logistic regression analysis showed that diabetes mellitus significantly increased the risk of albuminuria (OR: 1.543, P=0.000) and RI (OR: 1.446, P=0.005). Logistic regression analysis and multivariate regression analysis showed that although the deterioration trends of eGFR were similar in diabetes group and IGR group, IGR was not a significant risk factor for albuminuria or RI (OR:1.057, P=0.355; OR: 0.918, P=0.614). CONCLUSIONS: Diabetes mellitus is a significant risk factor for albuminuria and RI, while IGR is not. Screening for albuminuria and eGFR is highly recommended for individuals with diabetes, hypertension, and obesity, especially in women and the elderly population.

High prevalence of vitamin D deficiency among middle-aged and elderly individuals in northwestern China: its relationship to osteoporosis and lifestyle factors.

PURPOSE: Vitamin D deficiency has reached epidemic proportions; this deficiency has been associated with osteoporosis and certain lifestyle factors in adults. This relationship is not well documented among the Lanzhou population in northwest China. This study sought to determine the prevalence of vitamin D deficiency and its risk factors in addition to its relationship with osteoporosis in a Chinese population living in Lanzhou. METHODS: This cross-sectional study involved 2942 men and 7158 women aged 40-75years who were randomly selected from 3 communities in the Lanzhou urban district and examined medically. Levels of 25-hydroxy-vitamin D [25(OH)D] and other parameters were measured according to detailed inclusion criteria. Vitamin D deficiency was defined as serum 25(OH)D levels below 20ng/mL. Calcaneus bone mineral density (BMD) was measured by quantitative ultrasound (QUS). RESULTS: The prevalence of vitamin D deficiency (25(OH)D levels <20ng/mL) was present in 75.2% of the entire study population. Vitamin D deficiency was more prevalent in women (79.7%) than in men (64%; P<0.001). Multiple logistic regression analysis revealed that the significant predictors of vitamin D deficiency included coronary heart disease (CHD), obesity, dyslipidemia, older age, female sex, and smoking (all P<0.05), whereas tea intake, moderate physical activity, milk intake, vitamin D supplementation and sun exposure were protective (all P<0.05). No significant difference in calcaneus BMD measured by QUS was noted between subjects with <20ng/mL and ≥20ng/mL vitamin D levels (0.53±0.13 vs. 0.54±0.13; P=0.089). The risk of having osteoporosis did not increase when vitamin D levels decreased from ≥20ng/mL to <20ng/mL after multiple adjustments (OR=1.00; 95% CI 0.85-1.16; P=0.357). CONCLUSIONS: Vitamin D deficiency is prevalent in the middle-aged and elderly northwestern Chinese population and is largely attributed to CHD, obesity, dyslipidemia, older age, female sex, and smoking. Reduced 25(OH)D levels are not associated with an increased osteoporosis risk.

The status of 25-hydroxyvitamin D across the spectrum of glucose tolerance among middle-aged and elderly Chinese individuals.

CONTEXT: Although vitamin D status and its inverse association with diabetes among White people have been recognized, little research on vitamin D status has been well conducted in Chinese individuals based on glucose tolerance. OBJECTIVE: To compare the vitamin D status of Chinese individuals aged 40-75 years based on the glucose tolerance status. DESIGN AND METHODS: Serum 25OHD was measured in a cross-sectional sample of 10 038 individuals aged 40-75 years from Lanzhou city, which is located in western China. RESULTS: People with normal glucose tolerance (NGT, n = 4744), prediabetes (n = 2808) or diabetes (n = 2486) aged 40-75 years were included in the study. The difference in 25OHD concentration between people with NGT and prediabetes was not significant (16·5 vs 16·0 ng/ml, P = 0·773), but the 25OHD concentration of diabetes was higher than that of subjects with NGT (16·5 vs 16·5 ng/ml, P = 0·025) and prediabetes (16·5 vs 16·0 ng/ml, P = 0·032) after adjusting confounders. There was no difference in the prevalence of vitamin D deficiency between people with NGT and diabetes (74·7% vs 74·0%, P = 0·535), but the prevalence of vitamin D deficiency of prediabetes was higher than that of people with NGT (77·0% vs 74·7%, P = 0·024) and diabetes (77·0% vs 74·0%, P = 0·012). CONCLUSIONS: Although vitamin D status was significantly different across the spectrum of glucose tolerance in middle-aged and elderly Chinese individuals, the difference was not clinically significant. The results, however, highlight the very high prevalence of vitamin D deficiency in this population and should raise the awareness of this important public health issue among health-care providers.