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.

Folate ameliorates homocysteine-induced osteoblast dysfunction by reducing endoplasmic reticulum stress-activated PERK/ATF-4/CHOP pathway in MC3T3-E1 cells.

INTRODUCTION: Homocysteine (Hcy) is considered a newly identified risk factor for osteoporosis. Nevertheless, the underlying mechanism of folate (FA), a key factor in the metabolism of Hcy, in protection against osteoblast dysfunction remains unclear. The purpose of this study was to investigate the mechanism by which FA attenuates Hcy-induced osteoblast damage. MATERIALS AND METHODS: The Hcy-induced MC3T3-E1 cells were treated with different concentrations of FA. Cell morphology, cell density, cell proliferation ability, alkaline phosphatase (ALP) activity and mineralization capacity were observed and determined; the gene expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) and ERS-associated factors, including glucose-regulated protein 78 (GRP-78), activating transcription factor 4 (ATF-4) and growth arrest and DNA damage inducible gene 153 (CHOP/GADD153), were assessed by RT-PCR; and protein levels of GRP-78 and ATF-4 were analyzed by western blotting. RESULTS: Hcy suppressed the proliferation, differentiation and mineralization ability of MC3T3-E1 cells in a concentration-dependent manner and activated the ERS signaling pathway. After intervention with different concentrations of FA, the cell viability and density, ALP activity, number of mineralized nodules, calcium content and Bcl-2 gene expression were all significantly increased, whereas the gene expression of GRP-78, CHOP/GADD153, ATF-4 and Bax was markedly downregulated, and protein levels of GRP-78 and ATF-4 were also markedly decreased. CONCLUSION: The adverse effects of Hcy on osteoblast differentiation are dose dependent. FA not only protects against osteoblasts apoptosis but also has a direct osteogenic effect on Hcy-induced osteoblasts, which could be partially mediated by inhibition of the PERK-activated ERS pathway.

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.

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.

Natural history of mild subclinical hypothyroidism in a middle-aged and elderly Chinese population: a prospective study.

Subclinical hypothyroidism (SCH) has a high global prevalence. Most SCH patients have mild cases (thyrotropin ≤10 mIU/L). Treatment recommendations for mild SCH are controversial, which raises concerns about the natural history of mild SCH. We aimed to clarify the natural history of mild SCH. This is a prospective population-based study. We measured thyroid function in 11,000 participants in the REACTION study and followed 505 newly diagnosed mild SCH patients aged 40-years or older between 2011 and 2014. Logistic regression analysis was used to seek baseline parameters associated with the natural outcomes of mild SCH. Among 505 mild SCH patients, 221 (43.8%) had persistent SCH, 251 (49.7%) reverted to euthyroidism, and 17 (3.4%) progressed to overt hypothyroidism (OH). Patients with higher baseline total cholesterol (TC, between 201.0-240.0 mg/dL or >240.0 mg/dL vs. <201.0 mg/dL, p = 0.048 and 0.006, respectively) or positive thyroid peroxidase antibodies (TPOAb, p = 0.009) had higher risks of progression to OH, while those with higher baseline creatinine (CR, between 0.71-0.80 mg/dL or >0.80 mg/dL vs. ≤0.65 mg/dL, p = 0.031 and 0.004, respectively), higher baseline thyrotropin (≥7 mIU/L, p < 0.001) or older (>60 years vs. ≤50 years, p = 0.012) had lower odds of reverting to euthyroidism. In conclusion, TPOAb and TC seem to be more important predictors of progression to OH than initial thyrotropin, whereas high baseline thyrotropin or CR were negative correlated with reversion to euthyroidism. The prognostic value of TC and CR in mild SCH should be considered.

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.

Advanced progress of the relationship between renin-angiotensin-aldosterone system inhibitors and cancers.

Hypertension and cancers are the most common causes of death in humans, as well as common co-diseases among elderly population. Studies have shown that hypertension is associated with carcinogenesis. The renin-angiotensin-aldosterone system (RAAS) is a crucial regulatory system of blood pressure, fluid, and electrolyte homeostasis, which plays an essential role in the pathogenesis of hypertension, whose mechanism is relatively clear. Studies have indicated that RAAS also widely exists in cancer tissues of different systems, which can affect the risk of cancers by stimulating cancer angiogenesis, participating in cancer-related oxidative stress, and regulating cancer-related immunity. Therefore, inhibiting RAAS activity seems beneficial to decreasing the risk of cancers. As one of the most commonly used antihypertensive drugs, RAAS inhibitors have been widely used in clinical practice. However, the conclusions of clinical studies on the relationship between RAAS inhibitors and cancers are not entirely consistent, which has been widely concerned by clinicians. The latest findings suggest that while RAAS inhibitors may reduce the risk of digestive cancers, respiratory cancers, urological cancers, gynecological cancers, and skin cancers, ACEIs may increase the risk of lung cancer, endometrial cancer, basal cell carcinoma, and squamous cell carcinoma. This article comprehensively reviews animal experiments, clinical studies, and meta-analyses on the relationship between RAAS inhibitors and cancers, to provide references for related studies in the future.

Chiglitazar attenuates high-fat diet-induced nonalcoholic fatty liver disease by modulating multiple pathways in mice.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide; however, effective intervention strategies for NAFLD are still unavailable. The present study sought to investigate the efficacy of chiglitazar, a pan-PPAR agonist, in protecting against NAFLD in mice and its underlying molecular mechanism. Male C57BL/6 J mice were fed a high-fat diet (HFD) for 8 weeks to generate NAFLD and the HFD was continued for an additional 10 weeks in the absence or presence of 5 mg/kg/d or 10 mg/kg/d chiglitazar by gavage. Chiglitazar significantly improved dyslipidemia and insulin resistance, ameliorated hepatic steatosis and reduced liver inflammation and oxidative stress in NAFLD mice. RNA-seq revealed that chiglitazar alleviated HFD-induced NAFLD in mice through multiple pathways, including fatty acid metabolism regulation, insulin signaling pathway, and AMPK signaling pathway. This study demonstrated the potential therapeutic effect of chiglitazar on NAFLD. Chiglitazar ameliorated NAFLD by modulating multiple pathways.

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism.

Hypertension and osteoporosis are common comorbidities among elderly individuals. Drug therapy has been widely used in clinical practice as the preferred antihypertensive treatment. Therefore, antihypertensive drugs have become some of the most commonly prescribed drugs in healthcare settings. However, antihypertensive drugs have different effects on bone metabolism. The results of animal and clinical studies on the effects of antihypertensive drugs on osteoporosis or fracture risk are controversial and have aroused widespread concern among clinicians. Recent studies found that angiotensin receptor blockers, selective ß-adrenergic receptor blockers, and thiazide diuretics might improve bone trabecular number and bone mineral density by stimulating osteoblast differentiation, reducing osteoclast generation, and other mechanism. Furthermore, nonselective ß-adrenergic receptor blockers and dihydropyridine calcium channel blockers were found to have no significant relationship with bone mineral density or bone strength, and α-adrenergic receptor blockers and loop diuretics might increase fracture risk by decreasing bone mineral density. This article aimed to review previous animal experiments, clinical studies, and meta-analyses focusing on the effects of different antihypertensive drugs on bone metabolism, and to provide a new approach for the prevention and treatment of osteoporosis.

Exposure to famine in every stage of life and the risk of osteoporosis and fractures later in life: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Data on the association between early-life famine exposure and osteoporosis and fractures remain limited and inconclusive. The aim of this study was to investigate the correlation between famine exposure and osteoporosis and fractures. METHODS: We performed a cross-sectional analysis using the first follow-up survey data from the China Cardiometabolic Disease and Cancer Cohort Study from 2014 to 2016. We classified 4807 Lanzhou participants into seven groups based on their birthday (non-exposed or exposed in the fetal stage, early childhood, mid-childhood, late childhood, adolescence, or early adulthood). And we combined the non-exposed and early-adulthood exposed groups as a control group, which was called "age balanced group". This age-balanced group was used as the control group to further evaluate the risk of osteoporosis and fracture. We used multiple logistic regression to estimate the association between famine exposure and the risk of osteoporosis (T-score ≤ -1.8 by QUS) and self-reported fracture. RESULTS: In women, compared to the age-balanced group, the odds ratios (95 % CI) for the risk of osteoporosis were 1.400(1.034, 1.897), 1.630(1.268, 2.095), 1.707(1.314, 2.218), 2.150(1.732.2.668) and 2.885(2.286,3.641) in the fetal stage, early childhood, mid-childhood, late childhood and adolescence famine-exposed cohorts. In men, no association between famine and osteoporosis was noted with exposed cohort compared with the age-balanced control cohort (p > 0.05). Interestingly, the association between famine exposure and fractures was slightly different from the above results: in women, the odds ratios (95 % CI) for fractures in mid-childhood famine exposure was 1.461(1.082,1.973), in late childhood famine exposure was 1.333(1.035,1.718) and in adolescence famine exposure was 1.607(1.239,2.085). However, compared to the age-balanced control cohort, men exposed to famine in early childhood (OR: 1.801, 95 % CI: 1.010,3.211) had a higher risk of fracture. CONCLUSION: Famine exposure in different life stage has adverse effects on bone health. Famine exposure in not only the period from gestation to infancy, but also childhood and adolescence was associated with an increased risk of osteoporosis, especially in women. Exposure to famine in childhood- (mid and late) and adolescence- life period is associated with fracture in women. But, in men early-childhood famine exposure was only associated with fracture.