Effects of obesity with reduced 25(OH)D levels on bone health in elderly Chinese people: a nationwide cross-sectional study.

Background: Obesity is often accompanied by lower 25(OH)D levels, whereas these two parameters exhibit opposite effects on bone health. It is uncertain what are the effects of lower 25(OH)D levels in obesity on bone health in elderly Chinese people. Methods: A nationally representative cross-sectional analysis of China Community-based Cohort of Osteoporosis (CCCO) was performed from 2016 to 2021, which consisted of 22,081 participants. Demographic data, disease history, Body mass index (BMI), bone mineral density (BMD), the levels of the biomarkers of vitamin D status and those of bone metabolism markers were measured for all participants (N = 22,081). The genes (rs12785878, rs10741657, rs4588, rs7041, rs2282679 and rs6013897) related to 25(OH)D transportation and metabolism were performed in a selected subgroup (N = 6008). Results: Obese subjects exhibited lower 25(OH)D levels (p < 0.05) and higher BMD (p < 0.001) compared with those of normal subjects following adjustment. The genotypes and allele frequency of rs12785878, rs10741657, rs6013897, rs2282679, rs4588 and rs7041 indicated no significant differences among three BMI groups following correction by the Bonferroni's method (p > 0.05). The levels of total 25(OH)D (ToVD) were significantly different among the GC1F, GC1S and GC2 haplotype groups (p < 0.05). Correlation analysis indicated that ToVD levels were significantly correlated with parathyroid hormone levels, BMD, risk of osteoporosis (OP) and the concentration levels of other bone metabolism markers (p < 0.05). Generalized varying coefficient models demonstrated that the increasing BMI, ToVD levels and their interactions were positively associated with BMD outcomes (p < 0.001), whereas the reduced levels of ToVD and BMI increased the risk of OP, which was noted notably for the subjects with reduced ToVD levels (less than 20.69 ng/ml) combined with decreased BMI (less than 24.05 kg/m2). Conclusion: There was a non-linear interaction of BMI and 25(OH)D. And higher BMI accompanied by decreased 25(OH)D levels is associated with increased BMD and decreased incidence of OP, optimal ranges exist for BMI and 25(OH)D levels. The cutoff value of BMI at approximately 24.05 kg/m2 combined with an approximate value of 25(OH)D at 20.69 ng/ml are beneficial for Chinese elderly subjects.

The prevalence of osteoporosis in China, a community based cohort study of osteoporosis.

Background: Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods: The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results: After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80-34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58-21.87%) and 38.05% (95% CI, 37.22-38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions: This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

Osteoporosis and Related Health Status Among the Elderly Urban Residents in Elderly-Care Inns in Beijing, a Multicenter DXA Survey.

Background: Identification of the high risk population for osteoporosis and timely prevention are the best strategies at present. Detailed epidemiological investigation in a well-defined population is necessary to explore the population-based characteristics and risk factors of osteoporosis, thus to facilitate better prevention programs. Method: In this prospective cross-sectional study, 1423 questionnaires were given out to the urban residents (female ≥ 40 years of age, male ≥50 years) who lived in the 27 Elderly-Care Inns interspersed among the seven central urban areas of Beijing. All participants were voluntary and underwent routine physical examination and spine and hip BMD measurements using the DXA instrument. The study protocols were approved by the Medical Ethics Committee of Dongzhimen Hospital, Beijing University of Chinese Medicine (JDZX2015079). Results: Altogether 1407 participants fulfilled the survey. Among 359 men, the prevalence of osteoporosis, osteopenia, and normal BMD were 18.1%, 56.6%, and 25.3%, respectively; among 1048 women, the corresponding figures were 40.3%, 42.8%, and 16.9%, respectively. After adjustment of age and BMI, both hands grip strength, height loss over 3 cm, serum levels of ß-CTx, PINP, and OST were the independent risk factors for osteoporosis in both men and women; besides, familial Alzheimer's disease history in men; and history of steatohepatitis and fracture, serum levels of PTH and ALT, age of menarche, age of menopause, and duration of menstruation in women were also risk factors of osteoporosis. In both genders, the cost-effective method, which adopted both hands grip strength, height loss over 3 cm, and medical history, indicated a good predictive ability to evaluate the risk of osteoporosis (in men AUC=0.730, 95%CI=0.642~0.817; in women AUC=0.769, 95%CI=0.724~0.813). Conclusions: In the population of elderly Beijing urban residents in Elderly-Care Inns, the prevalence of osteoporosis in women is higher than that in men and increases with aging more rapidly; the prevalence of osteopenia in men is higher than in women. The cost-effective method, including both hands grip strength, height loss over 3 cm, and familial Alzheimer's disease history in men; fracture and steatohepatitis history as well as menstrual history in women is recommended in identifying the high-risk subjects for osteoporosis.

Identification of ZEB2 as an Immune-Associated Gene in Endometrial Carcinoma and Associated with Macrophage Infiltration by Bioinformatic Analysis.

Endometrial cancer (EC) is the most common gynecological tumor arising from the endometrium. In this study, we use a published single-cell transcriptome profile of endometrial carcinoma (EC) to reveal the composition of immune cells and found an immunosuppressive environment since the presence of macrophage subtype M2 and exhausted CD8+ T cell markers. We focused on ZEB2 (Zinc finger E-box binding homeobox 2), a well-known player in epithelial to mesenchymal transition process, and we showed that ZEB2 is exclusively expressed in immune cells in single-cell transcriptome and, at the same time, downregulated in TCGA-UCEC (The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma) bulk RNA-seq data and negatively associated with tumor purity. Loss of ZEB2 protein in EC in normal endometrium and EC samples was validated in samples using immunohistochemistry (IHC) from HPA (Human Protein Atlas) database. Furthermore, we found ZEB2 was associated with immune infiltrations especially for macrophage using TIMER 2.0. Interestingly, ZEB2 prognostic significance differed under various macrophage and Th2 helper cell content using Kaplan-Meier Plotter analysis. More importantly, we showed that over 11% EC patients have somatic mutations of ZEB2 in EC samples collected from cBioportal and they have a lower body weight, earlier diagnosis age, and better overall survival and disease-free survival status compared with the unaltered group. Analysis in TIMER2.0 suggested that ZEB2 mutation would possibly change the composition of tumor-infiltrating lymphocytes. Taken together, by combining the results from single-cell data, bulk TCGA RNA-seq, and other online bioinformatic tools, we provided evidence that ZEB2 might have a unique role in the immune environment of EC. These results would provide a better insight into the pathogenetic process and ZEB2 might further be used an immunotherapeutic target of EC.

Polymorphisms of genes related to vitamin D metabolism and transportation and its relationship with the risk of osteoporosis: protocol for a multicentre prospective cohort study in China.

INTRODUCTION: Osteoporotic fracture is one of the most common causes of disability and a major contributor to medical care costs in many regions of the world. The polymorphisms of genes related to vitamin D metabolism and transportation are associated with variation in bone mineral density and the risk of osteoporosis. METHODS AND ANALYSIS: The China Community-based Cohort of Osteoporosis study is an observational, longitudinal, multicentre, prospective cohort study for middle-aged and older permanent residents of China, which has been ongoing in six cities since 2016. Female residents aged 45-80 years old and male residents aged 50-80 years old are identified through permanent resident lists. All the enrolled participants will complete questionnaires on their personal characteristics and histories. The bone mineral density of their lumbar vertebrae and left hip will be measured and serum bone metabolism parameters assessed. Polymorphisms of genes related to vitamin D metabolism and transportation will be detected, and their relationship with the risk of osteoporosis, and osteoporotic fracture, will be analysed. About 18 000 residents will be involved in the study. ETHICS AND DISSEMINATION: The study was approved by Institutional Ethics Board of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine (2016LCSY065). Results will be published in peer-reviewed journals. The results of this study are expected to improve the understanding of the association between polymorphisms of genes related to vitamin D metabolism and transportation and the risk of osteoporosis and osteoporotic fracture among middle-aged and older residents of China. TRIAL REGISTRATION NUMBER: NCT02958020.