The Analysis for Anemia Increasing Fracture Risk.

BACKGROUND Fractures are a major public health problem for elderly people throughout the world. Anemia is also a common, important health problem among elderly populations. The aim of this article was to estimate the association between anemia and fracture incidence via a systematic review and meta-analysis. MATERIAL AND METHODS The participant, intervention, observation, and study design (PICOS) reporting guidelines were followed, and databases were searched from their inception to May 2020 to identify relevant studies. When heterogeneity was significant, and a random-effects model was used. Subgroup analysis was conducted to explore the source of heterogeneity based on sex, study design, and region. RESULTS We found that anemia significantly increased fracture risk [relative risk (RR)=1.26, 95% confidence interval (CI)=1.14-1.39, P<0.001], specifically, hip fracture (RR=1.44, 95% CI=1.29-1.61), spine fracture (RR=1.15, 95% CI=1.08-1.23), and nonspine fracture (RR=1.42, 95% CI=1.33-1.52). Males with anemia had a 1.51-fold higher fracture risk, females had a 1.09-fold higher fracture risk. And the association was stronger in Asian (RR=1.22, 95% CI=1.07-1.40), but not in American and European study populations. CONCLUSIONS In conclusion, a significantly increased fracture risk was observed, and anemia can be a predictor of fracture risk.

SEMA3B-AS1-inhibited osteogenic differentiation of human mesenchymal stem cells revealed by quantitative proteomics analysis.

Human mesenchymal stem cells (hMSCs) are fibroblastoid multipotent adult stem cells with capacities of differentiation into osteoblasts and chondrocytes and show great potential in new bone formation and bone repair-related clinical settings, such as osteoporosis. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in various biological processes. Here, we report an antisense lncRNA SEMA3B-AS1 regulating hMSCs osteogenesis. SEMA3B-AS1 is proximal to a member of the semaphorin family Sema3b. Overexpression of SEMA3B-AS1 using the lentivirus system markedly inhibits the proliferation of hMSCs and meanwhile reduces osteogenic differentiation. Using a comprehensive proteomic technique named isobaric tag for relative and absolute quantitation, we found that SEMA3B-AS1 significantly alters the process of osteogenesis through downregulating the expression of proteins involved in actin cytoskeleton, focal adhesion, and extracellular matrix-receptor interaction, while increasing the expression of proteins in the spliceosome. Collectively, we find that SEMA3B-AS1 is a target for controlling osteogenesis of hMSCs.

Deciphering the chromatin spatial organization landscapes during BMMSC differentiation.

The differentiation imbalance in bone marrow mesenchymal stem cells (BMMSCs) is critical for the development of bone density diseases as the population ages. BMMSCs are precursor cells for osteoblasts and adipocytes; however, the chromatin organization landscapes during BMMSC differentiation remain elusive. In this study, we systematically delineate the four-dimensional genome and dynamic epigenetic atlas of BMMSCs by RNA sequencing, assay for transposase-accessible chromatin sequencing, and high-throughput chromosome conformation capture. The structure analyses reveal 17.5% common and 28.5%-30% specific loops among BMMSCs, osteoblasts, and adipocytes. The subsequent correlation of genome-wide association studies and expression quantitative trait locus (eQTL) data with multi-omics analysis reveal 274 genes and 3634 single nucleotide polymorphisms (SNPs) associated with bone degeneration and osteoporosis (OP). We hypothesize that SNP mutations affect transcription factor (TF) binding sites, thereby affecting changes in gene expression. Furthermore, 26 motifs, 260 TFs, and 291 SNPs are identified to affect the eQTL. Among these genes, DAAM2, TIMP2, and TMEM241 are found to be essential for diseases such as bone degeneration and OP and may serve as potential drug targets.

A pooled analysis of the association between sarcopenia and osteoporosis.

BACKGROUND: Sarcopenia is a progressive generalized skeletal muscle disorder that causes the accelerated loss of muscle mass and function. Osteoporosis is a systemic condition of the skeleton that results in low bone mass and quality. Several studies have suggested that osteoporosis and sarcopenia are interrelated; however, a few studies indicate the lack of a significant association between sarcopenia and osteoporosis. We aimed to evaluate the association between sarcopenia and osteoporosis via a systematic review and pooled analysis. METHODS: From the inception of the PubMed and Embase databases until September 2022, we conducted a systematic search for studies evaluating the relationship between sarcopenia and osteoporosis. Study appraisal and synthesis methods: We included observational studies that provided 95% confidence intervals (CIs) and risk estimates. Two reviewers independently extracted data and assessed the quality of the research. The random-effects model was applied to the pool analysis, and the odds ratios (ORs) and 95% CIs were finally calculated. RESULTS: The primary statistic was the mutual risk between sarcopenia and osteoporosis. According to the inclusion criteria, 56 studies (796,914 participants) were finally included. Sarcopenia was significantly correlative to the risk of osteoporosis (OR, 3.06; 95% CI, 2.30-4.08), and each standard deviation increase in relative appendicular skeletal muscle mass was significantly related to a decreased risk of osteoporosis (OR, 0.65; 95% CI, 0.56-0.75). Osteoporosis observably referred to a higher risk of sarcopenia (OR, 2.63; 95% CI, 1.98-3.49). CONCLUSION: Our research indicated that sarcopenia and osteoporosis are highly positively correlated. Osteoporosis is closely associated with the risk of sarcopenia. Our finding highlights the importance of sarcopenia screening for those at risk of osteoporosis, and vice versa. However, heterogeneity was noted among the studies, and this might have influenced the accuracy of the results. Therefore, the results of our study should be interpreted with caution.

Impact of renal function on the prognosis of acute pulmonary embolism patients: a systematic review and meta-analysis.

OBJECTIVES: We conduct a study to explore the influence of impaired renal function on prognosis in Acute pulmonary embolism (APE) patients. METHODS: A meta-analysis was performed using the EMBASE and PubMed databases for relevant publications reporting the impact of impaired renal function on the clinical outcomes in patients with APE. RESULTS: Eventually, 17 articles were included in our analysis. The results suggested that renal insufficiency (RI) is a predictor of poor prognosis in APE patients(short-term mortality: pooled OR = 2.83, 95%CI: 2.20-3.63; long-term mortality: pooled OR = 2.30, 95%CI: 1.72-3.08; adverse outcomes: pooled OR = 3.02, 95%CI: 2.60-3.51). The short-term and long-term mortality rates of APE patients with RI were both higher than those in patients without RI. In addition, acute kidney injury(AKI) could serve as a predictive factor of poor prognosis (pooled OR = 2.75, 95%CI: 2.45-3.08), and it doubles the overall mortality rate in APE patients. However, chronic kidney disease (CKD) did not predict poor prognosis in APE patients (pooled OR = 1.94, 95%CI: 0.99-3.81), although it could slightly increase the overall mortality rate in APE patients. CONCLUSIONS: RI and AKI could be included in the prognosis evaluation for APE, but the impact of CKD in APE patients has yet to be determined.

Long non-coding RNA taurine upregulated gene 1 is downregulated in osteoporosis and influences the osteogenic differentiation of bone marrow mesenchymal stem cells.

BACKGROUND: With aging, an imbalance in bone remodeling leading to increased bone resorption and decreased bone formation is thought to contribute to osteoporosis. Osteoblastic differentiation of bone marrow mesenchymal stem cells (BMMSCs) plays a vital role in the pathogenesis of osteoporosis. However, the detailed molecular mechanisms of osteoporosis remain incompletely understood. Given that long non-coding RNA taurine upregulated gene 1 (lnc TUG1) plays a critical role in the osteogenic differentiation, and microRNA-23b (miR-23b) as a putative sponge for lnc TUG1 has upregulated expression in osteoporosis. Therefore, this study investigated the roles of TUG1/miR-23b in osteoporotic pathology. MATERIAL AND METHODS: TUG1 and miR-23b expression in the plasma of osteoporotic patients were evaluated by quantitative real-time PCR (qRT-PCR). The osteogenic differentiation in human BMMSCs was evaluated by qRT-PCR, western blot, Alizarin red staining after knockdown of TUG1 by small interfering RNA (siRNA) treatment. RESULTS: Decreased expression of TUG1 and increased expression of miR-23b evident in the plasma of patients with osteoporosis than in that of age- and sex-matched healthy controls. Additionally, increased miR-23b expression inhibited runt-related transcription factor 2 (RUNX2), osteocalcin, and osteopontin expression and reduced calcified nodule formation based on the results of qRT-PCR, western blot, and Alizarin Red S staining. CONCLUSION: The study for the first time reported that silence of lncRNA TUG1 significantly suppressed the osteogenic differentiation of BMMSCs possibly by targeting the miR-23b/RUNX2 signaling pathway. This mechanism of TUG1/miR-23b/RUNX2 signaling within the osteogenic differentiation of BMMSCs might provide new insight for the development of lncRNA-directed diagnostic and therapeutic strategies for osteoporosis.

An updated analysis of opioids increasing the risk of fractures.

OBJECTIVE: To assess the relationship between opioid therapy for chronic noncancer pain and fracture risk by a meta-analysis of cohort studies and case-control studies. METHODS: The included cohort studies and case-control studies were identified by searching the PubMed and EMBASE databases from their inception until May 24, 2019. The outcome of interest was a fracture. This information was independently screened by two authors. When the heterogeneity among studies was significant, a random effects model was used to determine the overall combined risk estimate. RESULTS: In total, 12 cohort studies and 6 case-control studies were included. We used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included literature, and 14 of the studies were considered high-quality studies. The overall relative risk of opioid therapy and fractures was 1.78 (95% confidence interval (CI) 1.53-2.07). Subgroup analyses revealed sources of heterogeneity, sensitivity analysis was stable, and no publication bias was observed. CONCLUSIONS: The meta-analysis showed that the use of opioids significantly increased the risk of fracture.