Prevalence and Risk Factors of Osteoporosis in a Chinese Population: A Cross-Sectional Study in Xi'an, Shaanxi Province, China.

BACKGROUND Osteoporosis is a systemic chronic disease characterized by bone mineral density (BMD) reduction. This study aimed to assess the prevalence of osteoporosis and fracture risks in northwestern China and investigate the related anthropometric risk factors. MATERIAL AND METHODS Between July 2022 and August 2022, 1429 participants (1295 females, 134 males) with measured BMD were recruited to participate in this cross-sectional study. Data on height, weight, and T score were collected. Spearman's correlation and multiple linear regression analysis were used to investigate the relationships between various demographic factors and BMD and the 10-year risk of major osteoporotic fracture (MO) and hip fracture (HP). RESULTS The overall prevalence of osteoporosis in northwest China was 42.34%, with 44.56% in females and 20.90% in males. Age negatively affects females' T scores (r=-0.304, P<0.05), and height positively influences both sexes' T scores (r=0.059 P<0.05). Age (r=0.148, P<0.05) and height were positive predictors of MO (r=0.027, P<0.05), while weight was a negative predictor (r=-0.035, P<0.05). The conclusion for HP was consistent with that of MO, except for the T score, which was a positive predictor of HP (r=0.014, P<0.05). CONCLUSIONS The prevalence of osteoporosis in northeast China is high. The association between anthropometric parameters and osteoporosis in adults in northwest China is different between sexes.

Wnt pathway in bone: knowledge structure and hot spots from 1993 to 2022.

Background: The role of the Wnt pathway in bone and its targets in skeletal disease has garnered interest, but the field lacks a systematic analysis of research. This paper presents a bibliometric study of publications related to the Wnt signaling pathway in bone to describe the current state of study and predict future outlooks. Methods: All relevant articles and reviews from 1993 to 2022 were collected from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using CiteSpace 6.1 R3, VOSviewer 1.6.15, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com/). Results: A total of 7,184 papers were retrieved, authored by 28,443 researchers from 89 countries/regions and published in 261 academic journals. The annual publication numbers peaked in 2021. China and United States are the leading countries, with the University of California and Harvard University as the most active institutions. Wang, Yang is the most prolific author. Bone has the most published research, while Proceedings of the National Academy of Sciences of the United States is the most cited journal on average. The main keywords include expression, Wnt, osteoporosis, bone, and osteogenic differentiation. Current and developing research hotspots focus on bone mass, sclerostin antibody, multiple myeloma, and cartilage development. Conclusion: This paper provides new insights for researchers to delve into the mechanisms of Wnt and bone related diseases and translate into clinical studies. It reveals the development and future research trends in Wnt and skeletal-related studies.

Causal associations of hand grip strength with bone mineral density and fracture risk: A mendelian randomization study.

Background: Muscle strength has been shown to exert positive effects on bone health. The causal relationship between hand grip strength and osteoporosis is an important public health issue but is not fully revealed. The goal of this study was to investigate whether and to what extent hand grip strength affects bone mineral density (BMD) and fracture risk. Methods: We conducted a state-of-the-art two-sample Mendelian randomization analysis. Genomewide significant (P<5×10-8) single nucleotide polymorphisms associated with hand grip strength were obtained. Summary level data of BMD and fractures at different body sites (lumbar spine, heel, forearm and femoral neck) was obtained from a large-scale osteoporosis database. The inverse variance weighted method was the primary method used for analysis, and the weighted-median, MR-Egger were utilized for sensitivity analyses. Results: The results provided strong evidence that hand grip strength trait was causally and positively associated with lumbar spine BMD (ß: 0.288, 95% CI: 0.079 to 0.497; P=0.007), while no causal relationship was found between hand grip strength and BMD at heel (ß: -0.081, 95% CI: -0.232 to 0.070; P=0.295), forearm (ß: 0.-0.101, 95% CI: -0.451 to 0.248; P=0.571) or femoral neck (ß: 0.054, 95% CI: -0.171 to 0.278; P=0.639). In addition, no statistically significant effects were observed for hand grip strength on fracture risks (ß: -0.004, 95% CI: -0.019 to 0.012; P=0.662). Conclusions: This study showed a positive causal relationship between hand grip strength and lumbar BMD, which is the most common site of osteoporotic fracture, but did not find a causal relationship between hand grip strength and BMD of heel, forearm, or femoral neck. No statistically significant effect of hand grip strength on fracture risk was observed. This study indicates variations in the abilities of hand grip strength trait to causally influence BMD at different skeleton sites. These results should be considered in further studies and public health measures on osteoporosis prevention strategies.

Causal relationships between rheumatism and dyslipidemia: A two-sample Mendelian randomization study.

Background: Dyslipidemia is often observed in rheumatic diseases, such as ankylosing spondylitis (AS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), yet it remains to be detected whether rheumatic diseases have a causal effect on dyslipidemia. Methods: Significant (P < 5 × 10-8) and independent (r2 < 0.1) single-nucleotide polymorphisms in genome-wide association studies were selected as instrumental variables to conduct Mendelian randomization (MR) analysis. Inverse variance weighted, weighted median, and MR-Egger regression were adopted for the causal inference. Subsequently, sensitivity analysis was conducted to assess the stability and reliability of MR. Results: The MR results revealed positive causal relationships of AS with total cholesterol (TC) (ß = 0.089, 95% CI = 0.050 to 0.128, P = 6.07 × 10-6), low-density lipoprotein (LDL) (ß = 0.087, 95% CI = 0.047 to 0.127, P = 1.91 × 10-5), and high-density lipoprotein (HDL) (ß = 0.043, 95% CI = 0.001 to 0.074, P = 0.009). There was no causal effect of RA on TC (ß = 0.008, 95% CI = 4.86 × 10-4 to 0.017, P = 0.064), LDL (ß = 6.4 × 10-4, 95% CI = -0.008 to 0.007, P = 0.871), or HDL (ß = 0.005, 95% CI = -0.003 to 0.013, P = 0.200). Additionally, SLE had negative causal links for TC (ß = -0.025, 95% CI = -0.036 to -0.015, P = 4.42 × 10-6), LDL (ß = -0.015, 95% CI = -0.025 to -0.005, P = 0.003), and HDL (ß = -0.013, 95% CI = -0.021 to -0.004, P = 0.004). The results were stable and reliable. Conclusion: This study suggested positive causal effects of AS on TC, LDL, and HDL and negative causal effects of SLE on these cholesterol levels, which could provide much help for the pathogenesis and treatment of rheumatic disease patients with dyslipidemia.

The relationship between central obesity and bone mineral density: a Mendelian randomization study.

BACKGROUND: The relationship between obesity and osteoporosis is an important public health issue. The goal of this study was to investigate whether and to what extent central obesity traits affect bone mineral density (BMD). METHODS: We conducted a two-sample Mendelian randomization analysis. Genomewide significant single nucleotide polymorphisms associated with waist circumference, hip circumference, waist-to-hip ratio, waist circumference adjusted by body mass index (WCadjBMI), hip circumference adjusted by BMI (HCadjBMI) and waist-to-hip ratio adjusted by BMI (WHRadjBMI) were obtained from a large-scale database containing 224,459 samples. The BMD summary dataset was obtained from a UK Biobank database including 265,627 participants. RESULTS: The results provided strong evidence that the HCadjBMI trait was causally and negatively associated with BMD (ß: - 0.135, 95% CI - 0.216 to - 0.054; P = 0.001), while the WHR trait was causally and positively associated with BMD (ß: 0.194, 95% CI 0.062 to 0.325, P = 0.004). No significant effects were observed for other traits on BMD. CONCLUSIONS: This study indicates variations in the abilities of different central obesity traits to influence BMD. These results should be considered in further studies and public health measures on obesity and osteoporosis prevention strategies.

Identification of N-glycoproteins of hip cartilage in patients with osteonecrosis of femoral head using quantitative glycoproteomics.

N-glycosylation is a major post-translational modification of proteins and involved in many diseases, however, the state and role of N-glycosylation in cartilage degeneration of osteonecrosis of femoral head (ONFH) remain unclear. The aim of this study is to identify the glycoproteins of ONFH hip cartilage. Cartilage tissues were collected from nine patients with ONFH and nine individuals with traumatic femoral neck fracture. Cartilage glycoproteins were identified by glycoproteomics based on LC-MS/MS. The differentially N-glycoproteins including glycosites were identified in ONFH and controls. A total of 408 N-glycoproteins with 444 N-glycosites were identified in ONFH and control cartilage. Among them, 104 N-glycoproteins with 130 N-glycosites were significantly differential in ONFH and control cartilage, which including matrix-remodeling-associated protein 5, prolow-density lipoprotein receptor-related protein 1, clusterin and lysosome-associated membrane glycoprotein 2. Gene Ontology analysis revealed the significantly differential glycoproteins mainly belonged to protein metabolic process, single-multicellular organism process, proteolysis, biological adhesion and cell adhesion. KEGG pathway and protein-protein interaction analysis suggested that the significantly differential glycoproteins were associated with PI3K-Akt signalling pathway, ECM-receptor interaction, protein processing in the endoplasmic reticulum and N-glycan biosynthesis. This information provides substantial insight into the role of protein glycosylation in the development of cartilage degeneration of ONFH patients.

Association of genetic defects in the apelin-AGTRL1 system with myocardial infarction risk in Han Chinese.

We aimed to test the hypothesis that apelin (APLN) and its receptor AGTRL1 (APLNR) genes may contribute to the pathogenesis of myocardial infarction in Han Chinese. This is a hospital-based, case-control association study, involving 1067 patients with myocardial infarction and 942 healthy controls. Myocardial infarction is diagnosed by electrocardiogram or anatomopathological examination. Eight polymorphisms in APLN gene and 5 in APLNR gene were genotyped using the TaqMan assay. Risk was summarized as odds ratio (OR) and 95% confidence interval (CI). In males, rs56204867-G allele (adjusted OR, 95% CI, p: 0.21, 0.08-0.55, 0.002) and rs2235309-T allele (0.60, 0.42-0.84, 0.004) was associated with a significantly reduced risk of myocardial infarction, and the mutations of rs2235310 was associated with an increased risk (1.41, 1.06-2.52, 0.021), as well as for rs948847-GG genotype (1.85, 1.23-2.91, 0.007). In females, the presence of rs56204867-AG and -GG genotypes was significantly associated with 44% and 50% reduced risk (0.56 and 0.50, 0.40-8.04 and 0.29-0.86, 0.007 and 0.036), respectively; for rs2235310, CC genotype was associated with 72% increased risk (1.72, 1.09-3.22, 0.016), and the odds of myocardial infarction was 3.47 for rs9943582-TT genotype (95% CI: 1.53-7.57, 0.009). The gender-specific association of APLN and APLNR genes with myocardial infarction was reinforced by further linkage and haplotype analyses. Finally, nomograms based on significant polymorphisms are satisfactory, with the C-indexes over 80% for both genders. Taken together, our findings indicate that APLN and APLNR genes are potential candidates in the pathogenesis of myocardial infarction in Han Chinese, and importantly their contribution is gender-dependent.

The Relationship Between Body Mass Index and Bone Mineral Density: A Mendelian Randomization Study.

Body mass index (BMI) is closely associated with bone mineral density (BMD) in both men and women. However, the relationship between BMI and BMD varies according to different studies. Using SNPs strongly associated with BMI in 336,107 individuals, we conducted a two-sample Mendelian randomization study to identify whether and to what extent BMD at different skeletal sites was affected by BMI. A power calculation was also performed. We found that BMI may causally increase lumbar BMD (ß 0.087; 95% CI 0.025 to 0.149; P = 0.006) and heel calcaneus BMD (ß 0.120; 95% CI 0.082 to 0.157; P = 1 × 10-7). The associations of BMI with forearm and femoral neck BMD were not statistically significant. Our study suggested that higher BMI plays a causal role in increasing BMD and the effects are similar across the skeleton. BMI was causally and positively associated with lumbar and heel calcaneus BMD. However, no statistically significant effects were observed for BMI on femoral neck or forearm BMD.

Effects of delayed hip replacement on postoperative hip function and quality of life in elderly patients with femoral neck fracture.

BACKGROUND: For various reasons, some elderly patients with femoral neck fracture undergo delayed surgical treatment. There is little information about the effect of delayed treatment on postoperative hip function and quality of life. The aim of this study was to investigate the effect of delayed hip arthroplasty on hip function, quality of life, and satisfaction in patients with femoral neck fractures. METHODS: Forty-seven patients with femoral neck fracture and hip replacement delayed over 21 days served as the delayed group (D group). Patients with femoral neck fracture, matched 1:1 for age and sex, and hip replacement within 7 days served as the control group (C group). The Harris hip score (HHS) and health-related quality of life (HRQoL) were assessed before surgery and 3 months, 6 months and 1 year postoperatively. The satisfaction questionnaires were completed by the patients themselves at the last follow-up. RESULTS: The HHS in the C group was lower than that in the D group (32.64 ± 9.11 vs. 46.32 ± 9.88, P < 0.05) before surgery but recovered faster after surgery. The HHS in the D group was lower than that in the C group 1 year postoperatively (85.2 ± 3.80 vs. 89.8 ± 3.33, P < 0.05). The patients' quality of life changed similarly to their HHS. The HHS 1 year after surgery was related to the preoperative HHS in group D (rs = 0.521, P < 0.01). Patients in the D group showed significantly higher satisfaction scores than those in the C group (P < 0.05). CONCLUSIONS: Hip function in patients with femoral neck fracture surgery delayed over 21 days recovered more slowly than that in those who underwent surgery within 7 days. However, they were more satisfied with the surgery. Moderate hip movement to ameliorate the lower limb muscle atrophy was recommended for patients facing a temporary inability to undergo surgery.

Isoform 1 of Fibrinogen Alpha Chain Precursor is a Potential Biomarker for Steroid-Induced Osteonecrosis of the Femoral Head.

PURPOSE: Early diagnosis is crucial to increase the chances of conservation treatment for patients with steroid-induced osteonecrosis of the femoral head (SIONFH). This study aimed to identify serum peptides as potential biomarkers to diagnose SIONFH. EXPERIMENTAL DESIGN: The serum proteome of 32 SIONFH patients and 24 healthy controls are analyzed using magnetic bead-based weak cation exchange (MB-WCX) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). Next, candidate biomarkers are identified using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Candidate biomarkers are then validated using ELISA and western blotting. RESULTS: 39 peaks are identified and the expression fold changes of seven peaks in the two groups are greater than 1.5. Three peaks (m/z: 1077.84 Da; m/z: 1061.78 Da; m/z: 1099.56 Da) tend to be upregulated, while four peaks (m/z: 3973.92 Da; m/z: 7766.53 Da; m/z: 3957.31 Da; m/z: 4212.02 Da) tend to be down-regulated in SIONFH patients. The peak for a 1077.84 Da peptide is identified as Isoform 1 of the Fibrinogen alpha chain precursor (FGA). ELISAs and western blot analyses reveal that the expression of FGA is significantly higher in SIONFH patients than healthy controls. CONCLUSION AND CLINICAL RELEVANCE: FGA is overexpressed in SIONFH patients, and thus, is a novel potential biomarker for SIONFH.

Fluid shear stress induces Runx-2 expression via upregulation of PIEZO1 in MC3T3-E1 cells.

Mechanically induced biological responses in bone cells involve a complex biophysical process. Although various mechanosensors have been identified, the precise mechanotransduction pathway remains poorly understood. PIEZO1 is a newly discovered mechanically activated ion channel in bone cells. This study aimed to explore the involvement of PIEZO1 in mechanical loading (fluid shear stress)-induced signaling cascades that control osteogenesis. The results showed that fluid shear stress increased PIEZO1 expression in MC3T3-E1 cells. The fluid shear stress elicited the key osteoblastic gene Runx-2 expression; however, PIEZO1 silencing using small interference RNA blocked these effects. The AKT/GSK-3ß/ß-catenin pathway was activated in this process. PIEZO1 silencing impaired mechanically induced activation of the AKT/GSK-3ß/ß-catenin pathway. Therefore, the results demonstrated that MC3T3-E1 osteoblasts required PIEZO1 to adapt to the external mechanical fluid shear stress, thereby inducing osteoblastic Runx-2 gene expression, partly through the AKT/GSK-3ß/ß-catenin pathway.

Genome-wide DNA methylation profiling of hip articular cartilage identifies differentially methylated loci associated with osteonecrosis of the femoral head.

OBJECTIVE: Recent studies demonstrated a critical role of hip articular cartilage destruction in the development of osteonecrosis of the femoral head (ONFH). The aim of this study was to characterize the genome-wide DNA methylation profile of hip cartilage obtained from patients with ONFH and healthy subjects. METHODS: Hip articular cartilage specimens were collected from 15 ONFH patients (including 11 males and 4 females) and 15 control subjects (including 11 males and 4 females) with femoral neck fracture. The average ages of the ONFH patients and control subjects were 50.27 ±â€¯5.27 years and 61.67 ±â€¯3.38 years, respectively. Genome-wide DNA methylation profiles of 5 ONFH and 5 control cartilages were determined by Illumina HumanMethylation850 array. Differential methylation analysis of DNA methylation profiles were performed by the empirical Bayes moderated t-test of the limma package. Mass spectrograph (MS) analysis of 10 ONFH cartilages and 10 normal cartilages were performed to validate the results of genome-wide DNA methylation profiling. Immunohistochemistry (IHC) of 4 ONFH cartilages and 4 control cartilages were conducted to evaluate the expression levels of proteins encoded by identified differentially methylated genes. t-test was used to assess the significance of protein expression differences between ONFH patients and controls in IHC. RESULTS: We identified a total of 2872 differentially methylated CpG sites, annotated to 480 hypermethylated genes and 1335 hypomethylated genes for ONFH. The results of MS validation were consistent with that of genome-wide DNA methylation profiling. IHC further confirmed the increased protein expression of CARS (mean and 95%CI of superficial zone 59.67% [48.46, 56.14], and deep zone 31% [25.85, 30.61]), PDE4D (superficial zone 50.33% [33.64, 40.68] and deep zone 28.67% [10.81, 36.47]), ADAMTS12 (superficial zone 53.67% [36.01, 40.93] and deep zone 34.67% [22.56, 37.18]), LRP5 (superficial zone 59.63% [27.32, 39.61] and deep zone 22.95% [5.28, 19.29]), RUNX2 (superficial zone 52.58% [11.64, 31.33] and deep zone 35.01% [10.03, 27.44]) in ONFH articular cartilage. CONCLUSION: Our results suggest the implication of DNA methylation alterations in the development of ONFH, and provide novel clues for pathogenetic and therapeutic studies of ONFH.