Contralateral knee osteoarthritis is a risk factor for ipsilateral knee osteoarthritis progressing: a case control study.

BACKGROUND: Knee osteoarthritis (KOA) is a highly disabling disease, and studying its progression is crucial. However, it is still unclear whether the progression of ipsilateral knee osteoarthritis is influenced by contralateral knee osteoarthritis. METHODS: Data were collected from the OAI database and divided into two study cohorts (right/left KOA cohort). Each cohort had a target knee (right/left knee) and was further divided into two groups (exposure/control group). The demographic data of both cohorts were balanced at baseline by propensity score matching (PSM), and the data included rating scale and radiographic and clinical data. After checking for balance in the matched variables, we then compared the differences between the two groups in each cohort. Our primary focus was on the minimum joint space width (mJSW) of the target knee, which was measured four years after baseline. The secondary outcome was the arthroplasty rate of the target knee within nine years. RESULTS: In this study, a total of 678 participants were enrolled and matched. After 1:1 PSM of the baseline demographic data, 98 participants in the right KOA cohort (RKOAC) were successfully matched, and 117 participants in the left KOA cohort (LKOAC) were successfully matched. Furthermore, the standardized mean difference (SMD) of the matched variables in both cohorts was less than 0.25. After analyzing the outcome metrics, we found that the target knee had a significantly lower mJSW in the fourth year after baseline and a significantly greater arthroplasty rate within nine years in the exposed group than in the control group. RKOAC: mJSW (exposure: 2.6(1.1 ~ 3.6) vs. control: 3.3(2.0 ~ 4.2), P < 0.05), arthroplasty rate (exposure: 14(14.3%) vs. control: 4(4.1%), P < 0.05); LKOAC: mJSW (exposure: 3.1(2 ~ 3.9) vs. control: 3.4(2.6 ~ 4.2), P < 0.05), arthroplasty rate (exposure: 16(13.7%) vs. control: 7(6%), P < 0.05). CONCLUSIONS: Patients with knee osteoarthritis experienced greater progression of osteoarthritis when the contralateral knee was also affected.

Influence of Inflammatory Bowel Disease on Patients Undergoing Primary Total Joint Arthroplasty: A Systematic Review and Meta-analysis of Cohort Studies.

Background: Inflammatory bowel disease (IBD) is recognized as a global disease. Although IBD is commonly diagnosed in the young male population, it also occurs in patients aged >60 years. With the advent of an aging society, it is expected that an increasing number of patients with IBD will undergo total joint arthroplasty (TJA). Purpose: To assess the impact of IBD on the risk of complications and revision as well as the length of stay (LOS) and treatment costs after TJA. Study Design: Systematic review; Level of evidence, 4. Methods: Utilizing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, articles were searched in the PubMed/MEDLINE, Embase, and Cochrane Library databases from the date of inception to August 31, 2022, using the following search terms: (1) "Inflammatory Bowel Diseases"[MeSH] and (2) "Arthroplasty, Replacement"[MeSH]. The study quality was scored according to the Newcastle-Ottawa Scale. A fixed-effects or random-effects model was used to calculate odds ratios or mean differences with 95% confidence intervals. Results: Of 232 studies initially retrieved, 8 retrospective cohort studies consisting of 33,758 patients with IBD and 386,238 patients without IBD were included. Patients with IBD had a higher incidence of complications (P < .05), readmission and revision (P < .05), experienced a longer LOS (P < .01), and paid higher treatment costs after TJA compared with patients without IBD . Conclusion: The results of our review demonstrated that IBD increased the risk of postoperative complications, prolonged the LOS, and increased treatment costs.

Analysis of Zinc and Stromal Immunity in Disuse Osteoporosis: Mendelian Randomization and Transcriptomic Analysis.

OBJECTIVE: Disuse osteoporosis is known to be primarily caused by a lack of exercise. However, the causal relationships between zinc and immunity and disuse osteoporosis remain unknown. This study investigated these relationships and their potential mechanisms. METHODS: This study was an integrative study combining genome-wide association studies and transcriptomics. Two-sample Mendelian randomization analysis (MR) was used to analyze the causal relationships between exposures (zinc, immunity, physical activity) and the outcome (osteoporosis) with the aid of single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Four models, MR-Egger, inverse variance weighted, weighted median and MR-Pleiotrophy RESidual Sum and Outlier (MRPRESSO), were used to calculate odds ratio values. Sensitivity and heterogeneity analyses were also performed using MRPRESSO and MR-Egger methods. The mRNA transcriptomic analysis was subsequently conducted. Zinc metabolism scores were acquired through single-sample Gene Set Enrichment Analysis algorithms. Stromal scores were obtained using the R Package "estimate" algorithms. Important Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways were also derived through gene set variation analysis. Cytoscape software helped construct the transcription factor (TF)-mRNA-microRNA (miRNA) network. Virtual screening and molecular docking were performed. Polymerase chain reaction validation was also carried out in vivo. RESULTS: Causal relationships were demonstrated between zinc and exercise (95% confidence interval [CI] = 1.30-2.95, p = 0.001), exercise and immunity (95% CI = 0.36-0.80, p = 0.002), exercise and osteoporosis (95% CI = 0.97-0.99, p = 0.0007), and immunity disorder and osteoporosis (95% CI = 1.30-2.03, p = 0.00002). One hundred and seventy-nine mRNAs in important modules were screened. Combining the differential expressional genes (DEGs) and the Boruta selection, six DEGs were screened (AHNAK, CSF2, ADAMTS12, SRA1, RUNX2, and SLC39A14). TF HOXC10 and miRNA hsa-miR-204 were predicted. Then, the TF-mRNA-miRNA network was successfully constructed. RUNX2 and SLC39A14 were identified as hub mRNAs in the TF-mRNA-miRNA network. Eventually, the novel small drug C6O4NH5 was designed according to the pharmacophore structure of SLC39A14. The docking energy for the novel drug was -5.83 kcal/mol. SLC39A14 and RUNX2 were downregulated (of statistical significance p-value < 0.05) in our animal experiment. CONCLUSION: This study revealed that zinc had a protective causal relationship with disuse osteoporosis by promoting exercise and immunity. SLC39A14 and RUNX2 mRNA participated in this zinc-related mechanism.

Mining Potential Drug Targets for Osteoporosis Based on CeRNA Network.

OBJECTIVE: To identify key pathological hub genes, micro RNAs (miRNAs), and circular RNAs (circRNAs) of osteoporosis (OP) and construct their ceRNA network in an effort to explore the potential biomarkers and drug targets for OP therapy. METHODS: GSE7158, GSE201543, and GSE161361 microarray datasets were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by comparing OP patients with healthy controls and hub genes were screened by machine learning algorithms. Target miRNAs and circRNAs were predicted by FunRich and circbank, then ceRNA network were constructed by Cytoscape. Pathways affecting OP were identified by functional enrichment analysis. The hub genes were verified by receiver operating characteristic (ROC) curve and real time quantitative PCR (RT-qPCR). Potential drug molecules related to OP were predicted by DSigDB database and molecular docking was analyzed by autodock vina software. RESULTS: A total of 179 DEGs were identified. By combining three machine learning algorithms, BAG2, MME, SLC14A1, and TRIM44 were identified as hub genes. Three OP-associated target miRNAs and 362 target circRNAs were predicted to establish ceRNA network. The ROC curves showed that these four hub genes had good diagnostic performance and their differential expression was statistically significant in OP animal model. Benzo[a]pyrene was predicted which could successfully bind to protein receptors related to the hub genes and it was served as the potential drug molecules. CONCLUSION: An mRNA-miRNA-circRNA network is reported, which provides new ideas for exploring the pathogenesis of OP. Benzo[a]pyrene, as potential drug molecules for OP, may provide guidance for the clinical treatment.