Unveiling the Hidden Link: Stomach Disease as a Risk Factor for Knee Osteoarthritis

Unveiling the Hidden Link: Stomach Disease as a Risk Factor for Knee Osteoarthritis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Unveiling the Hidden Link: Stomach Disease as a Risk Factor for Knee Osteoarthritis Xing Yang, Xi Yang, Ping Li, Hong Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5364266/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The knee joint is one of the most frequently affected joints in osteoarthritis (OA). However, the specific connection between gastric diseases and the occurrence of knee osteoarthritis (KOA) is currently unclear. The objective of this study is to explore the potential association between gastric diseases and KOA using the China Health and Retirement Longitudinal Study (CHARLS) database. Methods A total of 1053 subjects with complete information in 2018 from CHARLS database were included. First, the baseline characteristics of these subjects (covariates such as gender, residence, and smoke) were compared. Then, the relationship between stomach diseases and KOA was explored through 3 weighted multivariate logistic regression models. Afterwards, risk stratification analyses were taken to further confirm the stability of the correlation between stomach disease and KOA risk in different populations. The receiver operating characteristic (ROC) curve of model 3 was plotted to verify the predictive efficiency of stomach disease in KOA risk. Results we divided the subjects into 2 groups: the KOA group (n = 71) and the control group (n = 982). The baseline characteristics table revealed that substantial differences in heart attack, kidney illness, stomach disease, as well as health status between the KOA and control groups. Model 1 had an odds ratio (OR) of 3.05 (95% confidence interval (CI) = 1.75–5.30, P < 0.001). After adjusting for location, gender, and smoke, model 2's OR was 3.02 (95% CI = 1.73–5.28, P < 0.001), while model 3's OR was 2.48 (95% CI = 1.37–4.47, P = 0.002). The 3 models demonstrated that stomach disease and KOA were significantly associated and stomach disease was a risk factor for KOA, and the other covariates did not change the relationship. Risk stratification analyses indicated a stable association between stomach disease and KOA risk across populations. The area under the curve (AUC) was 0.722, indicating that model 3 had a good predictive accuracy. Conclusion In this study, we furtherly explored the correlation between stomach disease and KOA, and certified that stomach disease was a risk factor for KOA, which provided a reference for the correlation analysis between them. Stomach disease Knee osteoarthritis CHARLS Logistic regression models Receiver operating characteristic Figures Figure 1 Figure 2 Figure 3 1. Introduction Osteoarthritis (OA) is a degenerative joint disorder which charactered by the breakdown of cartilage, leading to pain, stiffness, and reduced mobility, knee osteoarthritis is the most common type[ 1 , 2 ]. It severely affects the life quality of older adults, approximately 10–15% of the population over 60 years old is affected by OA [ 3 , 4 ]. Over decades studies, obesity, genetics, injury, morphological defects, and hormonal factors are the top risks [ 5 ]. However, due to the avascular character of cartilage, there is still no effective therapy for cartilage regeneration and treatment for osteoarthritis mainly focuses on symptom relief, improving function, and slowing disease progression[ 6 ]. Treatment strategies include: non-Pharmacological Therapies, exercise, weight management physical therapy and so on [ 7 , 8 ]. Often used as first-line therapy for mild pain; Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are used as first-line therapy for pain relief but with potential gastrointestinal side effects[ 9 , 10 ]. Intra-articular corticosteroid and hyaluronic acid are applied to control inflammation and maintain joint functions[ 11 , 12 ]. Recently, platelet-rich plasma (PRP) and mesenchymal stem cell (MSC) are being widely explored for their potential in cartilage regeneration[ 12 ]. However, Arthroplasty and Osteotomy are still the final method to rescue joint functions [ 13 , 14 ], early diagnose and intervention of osteoarthritis are still vital tasks of regeneration medicine. Stomach diseases encompass a range of gastrointestinal conditions, such as gastritis, peptic ulcers, and infections like Helicobacter pylori [ 15 ]. These conditions affect different organ systems. The Russell research indicating that stomach diseases are risk factors of osteoarthritis, there are notable epidemiological links between stomach diseases and osteoarthritis[ 16 ]: 1. The two diseases have shared risk factors: age, obesity, smoking and alcohol consumption can exacerbate both joint degeneration and gastrointestinal problems; 2. Chronic low-grade inflammation is a component of osteoarthritis and may influence gastrointestinal health. Inflammatory mediators could potentially contribute to mucosal damages in both the stomach and joints[ 17 ]. 3. Studies suggest that stomach infections could induce alterations in gut microbiota, which activates the gut-brain and gut-joint axis, affecting systemic inflammation and immune responses, and then influencing the development or progression of osteoarthritis[ 18 ]; 4. NSAIDs (Nonsteroidal anti-inflammatory drugs) usage, which are frequently prescribed to relief pain, inflammation and swelling in osteoarthritis patients[ 19 ]. Prolonged NSAIDs usage has an increased risk of developing stomach diseases due to the medication's side effects[ 20 , 21 ]. However, till now there has no systematic research exploring the links between osteoarthritis and stomach diseases. China is experiencing a significant demographic shift toward an aging society, driven by increased life expectancy and declining birth rates. The aging population in China has led to increasing degenerative diseases among the elderly population, posing substantial challenges to the healthcare system[ 22 ]. The China Health and Retirement Longitudinal Study (CHARLS) provides comprehensive data that can be used to investigate degenerative diseases related to China's rapidly aging population and inform therapeutic strategies[ 23 ]. By facilitating cross-disciplinary research on aging, health, and retirement issues, the CHARLS enabling physicians and researchers to better understand the challenges and develop more effective strategies to address these challenges[ 24 ]. One study used CHARLS to investigate the relationship between chronic diseases and functional disabilities among older adults[ 25 ]. The researchers revealed that multiple chronic conditions could significantly increase the risk of disability and emphases the importance of more effective management of chronic diseases[ 26 , 27 ]. Our study, based on the CHARLS database, explored the association between gastric diseases and knee osteoarthritis by constructing a weighted multivariate logistic regression model. Subsequently, verified the stability of the link between gastric diseases and knee osteoarthritis hrough risk stratification analysis and ROC curves. This study provides a reference for research on the correlation between gastric diseases and knee osteoarthritis. 2. Materials and methods 2.1 Participants in study Based on a nationally representative cohort of people over 45 years old using the CHARLS. A total of 28 provinces were covered in the survey. Moreover, all subjects provided informed consent before participating in the survey. The 20,866 participants with information on osteoarthritis in the knee in 2018 were contained in this investigation. Subjects with missing data on stomach disease and related covariates (gender, location, smoke, fractured hip, health status, heart attack, diabetes, hypertension, kidney disease, drinking frequency, and sleep) were excluded. Eventually, we selected 1,053 subjects. The specific exclusion criteria was shown in Fig. 1 . 2.2 Defining stomach disease and KOA There were 3 questions to determine if subjects have a KOA, (1) Has a doctor ever told you that you have arthritis or rheumatism? Subjects who answered “yes” were asked a second question: (2) Do you often have pain? Not at all, a little, some, more, or very much (DA041_W4)? When an affirmative answer is received (a little, some, more, very much), the subjects were asked a third question: (3) Which parts of the body were painful (DA042)? Subjects who answered “knee” were considered to be KOA patients. According to question in the questionnaire section (da007_10_): When asked "If you have been diagnosed with stomach disease by a doctor," participants who said "yes" were categorized as having stomach disease, while those who said "no" were classified as being in the control group, which did not have stomach disease. 2.3 Definition of covariates To assess the impact of potential confounders, a number of covariates were collected for this study, including gender (male and female), location (central of city/town, rural, special zone, and urban-rural integration zone), smoke (still smoke, quit, and never smoked), fractured hip (yes and no), health status (very good, good, fair, poor, and very poor), heart attack, diabetes, hypertension, kidney disease, sleep (optimal nighttime sleep duration (7–9 hours), short nighttime sleep duration (less than 7 hours), long nighttime sleep duration (more than 9 hours) [ 28 ], and drinking frequency ( none of these, drink but less than once a month, and drink more than once a month). 2.4 Statistical analysis In this study, for the description of subjects' baseline characteristics, categorical variables were expressed as percentages, and comparisons of differences in baseline characteristics were carried out through the chi-square test (categorical variables) or the t-test (continuous variables) between groups ( P < 0.05). The baseline characteristics was plotted by the compare Groups package (v 4.8.0) [ https://cran.r-project.org/package=compareGroups ]. The association between stomach disease and KOA was explored through 3 weighted multivariate logistic regression models by survey package (v 4.4.1) [ https://cran.r-project.org/package=survey ], and adjusted odds ratio (OR) and 95% confidence interval (95%CI) were calculated. In particular, model 1 solely took into account the impact of stomach disease on KOA and was left unaltered. Model 2 was modified to account for gender, location, as well as smoke. For each covariate, Model 3 was changed. Subsequently, to further confirm the stability of the correlation between gastric disorders and KOA risk across populations, the covariates were divided into subgroups for risk stratification analyses. Based on model 3, using the p ROC package (v 1.18.0) [ 29 ], the receiver operating characteristic (ROC) curve for model 3 was created. All statistical analyses were performed by the R language (v 4.2.2) and tidy verse package (v 2.0.0) [ https://doi.org/10.21105/joss.01686 ]. 3. Results 3.1 Baseline characteristics of individual subjects The baseline characteristics were shown in Table 1 . Of the 1,053 subjects included, there were 982 in the control group and 71 in the KOA group. The 964 females and 89 males made up the population, or 8.45% and 91.55%, respectively. The KOA group's sleep duration was noticeably shorter. Significant differences were seen in health status ( P = 0.014), heart attack ( P = 0.047), kidney disease ( P < 0.001), as well as stomach disease ( P < 0.001) between the KOA and control groups. 3.2 Stomach disease was a risk factor for KOA The relationship between stomach disease and KOA was explored by 3 weighted multivariate logistic regression models ( Table 2 ), and model 1 (OR: 3.05, 95% CI: 1.75–5.30) showed that stomach disease and KOA were significantly associated ( P < 0.001) (Fig. 2 A). After adjusting the location, gender and smoke, model 2 (OR: 3.02, 95% CI: 1.73–5.28) revealed that stomach disease and KOA were apparent associated ( P < 0.001). Based on model 2, after accounting for every covariate, the results of model 3 (OR: 2.48, 95% CI: 1.37–4.47) clearly demonstrated a connection between stomach disease and KOA ( P = 0.002). Models 2 and 3 demonstrated that adding covariates did not change the stable relationship between stomach disease and KOA. Stomach disease is a risk factor for KOA. By performing a risk stratification analysis of the covariates in model 2, gender, location, as well as smoke were found to have no significant association with the risk of KOA, and there was a direct and significant association between stomach disease and KOA (Fig. 2 B). After considering for all covariates, risk stratification demonstrated that there was a significant and stable association between stomach disease and and KOA (Fig. 2 C). These results suggested that there was an obvious correlation between stomach disease and KOA, also stomach disease was a risk factor for KOA. Furthermore, the plotted ROC curves' area under the curve (AUC) values was 0.722, indicating that model 3 had high accuracy in predicting the risk of KOA, and that stomach disease showed good predictive value for changes in the risk of KOA (Fig. 3 ). 4. Discussion KOA is a prevalent degenerative joint disease, particularly affecting the elderly population[ 30 ]. Gastrointestinal diseases, including gastritis, peptic ulcers, and other gastrointestinal disorders, are also more common in the elderly[ 31 ]. Understanding the potential association between stomach diseases and knee osteoarthritis can provide valuable insights for prevention and treatment strategies. Our study suggested that there was an obvious and stable correlation between stomach disease and KOA, stomach disease was a risk factor for KOA. The findings encourage researchers and physicians to explore more effective therapies for KOA treatment. Multiple personal habits, such as smoking, cardiovascular disease, and diabetes, were associated with an increased prevalence of OA and stomach problems[ 32 ], which are consistent with our findings. Our study revealed that the sleep duration of KOA group was noticeably shorter and showed significant differences in health status (P = 0.014), heart attack (P = 0.047), kidney disease (P < 0.001), as well as stomach disease (P < 0.001) between the KOA and control groups. Studies show that poor sleep quality and insomnia are prevalent in older adults and are associated with increased risk of multiple health problems[ 33 , 34 ]. Moreover, sleep disturbance may further affect the health status of the elderly by activating inflammatory mechanisms [ 35 , 36 ]. Therefore, improving sleep quality may be an important strategy for the prevention and management of osteoarthritis and other related health problems. Yan Ren et al. found that the presence of heart disease, kidney disease, and digestive system diseases may be associated with a higher risk of developing symptomatic KOA [ 26 ]. Some scholars believe that KOA has an independent correlation with an increased risk of CVD (cardiovascular disease).[ 37 ] Diabetes and kidney diseases are associated with the symptom progression of knee OA [ 38 , 39 ]; there is a close correlation between smoking and the risk of knee osteoarthritis [ 40 ]. Even though our data shows an possible link between heart attack and osteoarthritis, till now, the detailed underling association is still not clear, the coincidence largely due to shared risk factors [ 35 ].In summary, poor lifestyle habits or having multiple chronic diseases simultaneously can both increase the risk of KOA. Emerging research highlights that gastrointestinal disorders and osteoarthritis influence each other through several aspects, like the gut microbiota, gut-brain and gut-joint axis. Previous and our data showed a stable link between osteoarthritis and stomach diseases, the association may largely depend on the role of the gut microbiome and medication use[ 41 ]. Unhealthy gut microbiome healthy plays a key role in systemic inflammation, which allows inflammatory substances to enter the bloodstream, potentially exacerbating joint inflammation and contributing to OA progression[ 41 , 42 ]. Long-term use of high-dose NSAIDs of patients with osteoarthritis always may greatly increase the possibility of stomach diseases, and vice versa[ 43 ]. If stomach diseases occur, the OA therapy needs to be changed, which results in additional treatment costs and causes discomfort for both patients and clinicians[ 43 , 44 ]. Therefore, it is necessary to create a stomach disease prediction model that can reflect the detailed health status of each individual and to use it when making treatment plans. Although there is a paucity of direct research investigating the acceleration of joint degeneration by inflammatory molecules entering the bloodstream in digestive system diseases, this association theoretically exists. Emerging research highlights that gastrointestinal disorders and osteoarthritis influence each other through several aspects, like the gut microbiota, gut-brain and gut-joint axis[ 45 , 46 ]. Stomach diseases and gut microbiota and are closely interconnected[ 47 , 48 ]. Disturbances in microbial balance can contribute to stomach diseases such as gastritis, peptic ulcers, gastro esophageal reflux disease (GERD), and even stomach cancer[ 47 , 48 ]. Yaqiong Zhou et al. found through a Mendelian randomization study that patients with GERD have a higher risk of developing KOA, which warrants our serious attention[ 49 ]. Gastric diseases can lead to nutritional absorption issues for patients, resulting in health problems such as weight loss [ 50 ]. This subsequently affects the absorption of nutrients crucial for joint health, including calcium and vitamin D [ 51 ], thereby influencing the progression of KOA. These situations allow inflammatory molecules to enter the bloodstream[ 52 , 53 ], thus may be accelerate joint degeneration. The gut-brain axis can affect pain pathways in OA through neuroinflammatory processes[ 54 ]. Alterations in gut health may influence central pain processing, leading to heightened pain sensitivity or chronic pain conditions[55]. Long-term use of high-dose NSAIDs may greatly increase the possibility of gastric ulcers and reflux, disrupting the balances in the intestinal microbiome can elevate inflammation[ 56 ], complicating OA symptoms. This bidirectional relationship suggests the need for a balanced treatment strategy, focusing not only on joint management but also on stomach healthy. Therefore, it is necessary to create a stomach disease monitor model which can predict the occurrence of KOA and make more effective therapies. This study, for the first time, combines logistic regression modeling with risk stratification analysis to more precisely explore the complex relationship between gastric diseases and the risk of KOA. It fills a gap in the current literature regarding research on the association between gastric diseases and KOA risk, providing robust evidentiary support for a deeper understanding of the intrinsic connection between the two. This research holds significant guiding implications for future clinical practice and disease prevention. However, this study has a few limitations. First, we were unable to include enough OA patients to this study because of the database limitation, and could not engorge the bias caused by gender. Second, it was difficult to eliminate side effect of drugs, such as NSAIDs, aspirin, on the gastrointestinal mucosa, which certainly would increase the risk of stomach diseases, while these drugs could attenuate the symptoms of osteoarthritis, thus the data we obtained now could not support an accurate predictive model. Last, specific and accurate diagnose of stomach disease could only be obtained by gastric endoscopy and other clinical examines, and it was difficult to get reliably onset of stomach diseases because symptoms vary on the patient. Our study explored the prevalence of stomach diseases in the general population and osteoarthritis patients, and has provided new evidence to support stomach diseases as a risk factor for osteoarthritis. This study contributes to a deeper understanding of the potential association between stomach diseases and osteoarthritis, providing new ideas and directions for clinical prevention and treatment of osteoarthritis. Abbreviations OA Osteoarthritis KOA Knee osteoarthritis CHARLS China Health and Retirement Longitudinal Study ROC Receiver operating characteristic OR Odds ratio CI Cnfidence interval AUC Aea under the curve NSAIDs Nonsteroidal Anti-inflammatory Drugs PRP Patelet-rich plasma MSC Menchymal stem cell GERD Gestro esophageal reflux disease CVD Cdiovascular disease Declarations Acknowledgements The authors thank all participants of the CHARLS and all workers who collected the data. Authors’ contributions All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. HL and PL had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. XY and XY contributed equally to this work. PL and HL wrote the manuscript. All authors reviewed and approved the final version of the manuscript. Funding This study was supported by Scientific Research Project of Chongqing Doctor Direct Train (CSTB2022BSXM-JCX0084), Doctoral research start‐up fund of Chongqing University Three Gorges Hospital (ZX-50010101-2022-285) and Natural Science Foundation of Guangdong Province (2023A1515011572). Availability of data and materials All data collected in the CHARLS are maintained at the National School of Development of Peking University, Beijing, China. The datasets are available from http://charls.pku.edu.cn/pages/data/111/zh-cn.html. Ethics approval and consent to participate The current study is a secondary analysis of the CHARLS public data. No separate ethical approval was required for our study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The original CHARLS was approved by the Ethical Review Committee of Peking University, and all participants signed informed consent at the time of participation. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Ferrari AJ, Santomauro DF, Aali A, Abate YH, Abbafati C, Abbastabar H, Abd ElHafeez S, Abdelmasseh M, Abd-Elsalam S, Abdollahi A, et al. 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Jhun J, Woo JS, Kwon JY, Na HS, Cho K-H, Kim SA, Kim SJ, Moon S-J, Park S-H, Cho M-L. Vitamin D Attenuates Pain and Cartilage Destruction in OA Animals via Enhancing Autophagic Flux and Attenuating Inflammatory Cell Death. Immune Netw 2022, 22(4). Vianello E, Galliera E. New Molecular Mechanisms and Markers in Inflammatory Disorders. Int J Mol Sci 2024, 25(12). Lee YS, Olefsky J. Chronic tissue inflammation and metabolic disease. Genes Dev. 2021;35(5–6):307–28. Wei Z, Li F, Pi G. Association Between Gut Microbiota and Osteoarthritis: A Review of Evidence for Potential Mechanisms and Therapeutics. Front Cell Infect Microbiol 2022, 12. Tables Table 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.xlsx Table2.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5364266","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":374702549,"identity":"9769ca51-e121-4420-a1e4-68ce40867fff","order_by":0,"name":"Xing Yang","email":"","orcid":"","institution":"Minda Hospital of Hubei Minzu University","correspondingAuthor":false,"prefix":"","firstName":"Xing","middleName":"","lastName":"Yang","suffix":""},{"id":374702550,"identity":"2903c775-ad76-48d4-bd74-9d98335cd689","order_by":1,"name":"Xi Yang","email":"","orcid":"","institution":"The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture","correspondingAuthor":false,"prefix":"","firstName":"Xi","middleName":"","lastName":"Yang","suffix":""},{"id":374702551,"identity":"fe3377cc-ef83-40b5-bd19-19da0cd45db6","order_by":2,"name":"Ping Li","email":"","orcid":"","institution":"The third affiliated hospital of Sun Yat-sen university ・ Lingnan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Li","suffix":""},{"id":374702552,"identity":"15b93d56-05d8-4726-a5e8-8601b7b284d4","order_by":3,"name":"Hong Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYBACPmYGNgbGBgY5fvbmAwc+/CBCCxtUi7Fkz7HEgzN7iNHCANGSuOFGjvFhDjZitLDzmD3m3XEYaMuZD4cZeBjk+cUOEHIYj7kx75nDQL/0bjhcYMFgOHN2AkEtZtK5bSBbzm44PIOHIcHgNpFaQH55cJiHjUQtDMRqYSuT/tuWDgpkA2AgSxD2Cz//4W2SM9usQVH5+MOHHzby/NIEtKADCdKUj4JRMApGwSjADgA9ZEIpbHKxBAAAAABJRU5ErkJggg==","orcid":"","institution":"Chongqing University Three Gorges Hospital","correspondingAuthor":true,"prefix":"","firstName":"Hong","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-10-31 02:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5364266/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5364266/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69010680,"identity":"b316b77e-dfae-4b97-83f7-f57ddfaba57e","added_by":"auto","created_at":"2024-11-14 13:41:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":225329,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart showing the selection of the respondents who were included in the final analysis in this study.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote：This study utilized data from 20,866 research subjects in the 2018 CHARLS database. After excluding individuals with missing exposure factors and related covariate data, we successfully recruited 1,053 participants.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-5364266/v1/0001dbead543d37a1dde4431.png"},{"id":69010926,"identity":"838382d5-ff02-42be-884b-456381c32851","added_by":"auto","created_at":"2024-11-14 13:49:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":631848,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEvaluation of risk stratification and prediction efficacy for stomach diseases and KOA.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote：(A) The stratified analysis of patients with stomach disease and KOA in Model 1 revealed a statistically significant difference (p \u0026lt; 0.01). (B) A stratified analysis was performed on patients with stomach diseases and KOA using Model 2, yielding a significant result (p\u0026lt;0.01). (C) The stratified analysis of patients diagnosed with stomach diseases and KOA, as defined in Model 3, revealed a statistically significant result (p \u0026lt; 0.01).\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-5364266/v1/8e35eecfabe0848cb8d37086.png"},{"id":69011903,"identity":"73cecd75-fd53-4c64-a2dd-eda4532384d5","added_by":"auto","created_at":"2024-11-14 13:57:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":285822,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC curve area prediction model 3 in terms of KOA risk.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: The plotted ROC curves' area under the curve (AUC) values was 0.722.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-5364266/v1/a07be2fdcc0d1d02c26d0a3f.png"},{"id":99761046,"identity":"2827aede-8981-4b74-a70e-fc448e93e9d8","added_by":"auto","created_at":"2026-01-08 06:57:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1891370,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5364266/v1/7ac88b19-760c-4a16-abc4-c394f3a5ef0a.pdf"},{"id":69010683,"identity":"e9a8b8d4-1525-49c4-b820-0cd6dacd07fe","added_by":"auto","created_at":"2024-11-14 13:41:20","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":11540,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5364266/v1/1f3a3f58d02bd27cc52ef422.xlsx"},{"id":69010924,"identity":"080edac8-68b1-4cf1-99e1-207df7363d0d","added_by":"auto","created_at":"2024-11-14 13:49:20","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10631,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5364266/v1/a96847ecb2eb8bb6c87f469a.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unveiling the Hidden Link: Stomach Disease as a Risk Factor for Knee Osteoarthritis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOsteoarthritis (OA) is a degenerative joint disorder which charactered by the breakdown of cartilage, leading to pain, stiffness, and reduced mobility, knee osteoarthritis is the most common type[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It severely affects the life quality of older adults, approximately 10\u0026ndash;15% of the population over 60 years old is affected by OA [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Over decades studies, obesity, genetics, injury, morphological defects, and hormonal factors are the top risks [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, due to the avascular character of cartilage, there is still no effective therapy for cartilage regeneration and treatment for osteoarthritis mainly focuses on symptom relief, improving function, and slowing disease progression[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Treatment strategies include: non-Pharmacological Therapies, exercise, weight management physical therapy and so on [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Often used as first-line therapy for mild pain; Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are used as first-line therapy for pain relief but with potential gastrointestinal side effects[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Intra-articular corticosteroid and hyaluronic acid are applied to control inflammation and maintain joint functions[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Recently, platelet-rich plasma (PRP) and mesenchymal stem cell (MSC) are being widely explored for their potential in cartilage regeneration[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, Arthroplasty and Osteotomy are still the final method to rescue joint functions [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], early diagnose and intervention of osteoarthritis are still vital tasks of regeneration medicine.\u003c/p\u003e \u003cp\u003eStomach diseases encompass a range of gastrointestinal conditions, such as gastritis, peptic ulcers, and infections like \u003cem\u003eHelicobacter pylori\u003c/em\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These conditions affect different organ systems. The Russell research indicating that stomach diseases are risk factors of osteoarthritis, there are notable epidemiological links between stomach diseases and osteoarthritis[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]: 1. The two diseases have shared risk factors: age, obesity, smoking and alcohol consumption can exacerbate both joint degeneration and gastrointestinal problems; 2. Chronic low-grade inflammation is a component of osteoarthritis and may influence gastrointestinal health. Inflammatory mediators could potentially contribute to mucosal damages in both the stomach and joints[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. 3. Studies suggest that stomach infections could induce alterations in gut microbiota, which activates the gut-brain and gut-joint axis, affecting systemic inflammation and immune responses, and then influencing the development or progression of osteoarthritis[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]; 4. NSAIDs (Nonsteroidal anti-inflammatory drugs) usage, which are frequently prescribed to relief pain, inflammation and swelling in osteoarthritis patients[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Prolonged NSAIDs usage has an increased risk of developing stomach diseases due to the medication's side effects[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, till now there has no systematic research exploring the links between osteoarthritis and stomach diseases.\u003c/p\u003e \u003cp\u003eChina is experiencing a significant demographic shift toward an aging society, driven by increased life expectancy and declining birth rates. The aging population in China has led to increasing degenerative diseases among the elderly population, posing substantial challenges to the healthcare system[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The China Health and Retirement Longitudinal Study (CHARLS) provides comprehensive data that can be used to investigate degenerative diseases related to China's rapidly aging population and inform therapeutic strategies[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. By facilitating cross-disciplinary research on aging, health, and retirement issues, the CHARLS enabling physicians and researchers to better understand the challenges and develop more effective strategies to address these challenges[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. One study used CHARLS to investigate the relationship between chronic diseases and functional disabilities among older adults[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The researchers revealed that multiple chronic conditions could significantly increase the risk of disability and emphases the importance of more effective management of chronic diseases[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study, based on the CHARLS database, explored the association between gastric diseases and knee osteoarthritis by constructing a weighted multivariate logistic regression model. Subsequently, verified the stability of the link between gastric diseases and knee osteoarthritis hrough risk stratification analysis and ROC curves. This study provides a reference for research on the correlation between gastric diseases and knee osteoarthritis.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Participants in study\u003c/h2\u003e \u003cp\u003eBased on a nationally representative cohort of people over 45 years old using the CHARLS. A total of 28 provinces were covered in the survey. Moreover, all subjects provided informed consent before participating in the survey. The 20,866 participants with information on osteoarthritis in the knee in 2018 were contained in this investigation. Subjects with missing data on stomach disease and related covariates (gender, location, smoke, fractured hip, health status, heart attack, diabetes, hypertension, kidney disease, drinking frequency, and sleep) were excluded. Eventually, we selected 1,053 subjects. The specific exclusion criteria was shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Defining stomach disease and KOA\u003c/h2\u003e \u003cp\u003eThere were 3 questions to determine if subjects have a KOA, (1) Has a doctor ever told you that you have arthritis or rheumatism? Subjects who answered \u0026ldquo;yes\u0026rdquo; were asked a second question: (2) Do you often have pain? Not at all, a little, some, more, or very much (DA041_W4)? When an affirmative answer is received (a little, some, more, very much), the subjects were asked a third question: (3) Which parts of the body were painful (DA042)? Subjects who answered \u0026ldquo;knee\u0026rdquo; were considered to be KOA patients. According to question in the questionnaire section (da007_10_): When asked \"If you have been diagnosed with stomach disease by a doctor,\" participants who said \"yes\" were categorized as having stomach disease, while those who said \"no\" were classified as being in the control group, which did not have stomach disease.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Definition of covariates\u003c/h2\u003e \u003cp\u003eTo assess the impact of potential confounders, a number of covariates were collected for this study, including gender (male and female), location (central of city/town, rural, special zone, and urban-rural integration zone), smoke (still smoke, quit, and never smoked), fractured hip (yes and no), health status (very good, good, fair, poor, and very poor), heart attack, diabetes, hypertension, kidney disease, sleep (optimal nighttime sleep duration (7\u0026ndash;9 hours), short nighttime sleep duration (less than 7 hours), long nighttime sleep duration (more than 9 hours) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e28\u003c/span\u003e], and drinking frequency ( none of these, drink but less than once a month, and drink more than once a month).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e \u003cp\u003eIn this study, for the description of subjects' baseline characteristics, categorical variables were expressed as percentages, and comparisons of differences in baseline characteristics were carried out through the chi-square test (categorical variables) or the t-test (continuous variables) between groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The baseline characteristics was plotted by the compare Groups package (v 4.8.0) [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cran.r-project.org/package=compareGroups\u003c/span\u003e\u003cspan address=\"https://cran.r-project.org/package=compareGroups\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e]. The association between stomach disease and KOA was explored through 3 weighted multivariate logistic regression models by survey package (v 4.4.1) [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cran.r-project.org/package=survey\u003c/span\u003e\u003cspan address=\"https://cran.r-project.org/package=survey\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e], and adjusted odds ratio (OR) and 95% confidence interval (95%CI) were calculated. In particular, model 1 solely took into account the impact of stomach disease on KOA and was left unaltered. Model 2 was modified to account for gender, location, as well as smoke. For each covariate, Model 3 was changed. Subsequently, to further confirm the stability of the correlation between gastric disorders and KOA risk across populations, the covariates were divided into subgroups for risk stratification analyses. Based on model 3, using the p ROC package (v 1.18.0) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], the receiver operating characteristic (ROC) curve for model 3 was created. All statistical analyses were performed by the R language (v 4.2.2) and tidy verse package (v 2.0.0) [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.21105/joss.01686\u003c/span\u003e\u003cspan address=\"10.21105/joss.01686\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Baseline characteristics of individual subjects\u003c/h2\u003e \u003cp\u003eThe baseline characteristics were shown in \u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e. Of the 1,053 subjects included, there were 982 in the control group and 71 in the KOA group. The 964 females and 89 males made up the population, or 8.45% and 91.55%, respectively. The KOA group's sleep duration was noticeably shorter. Significant differences were seen in health status (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014), heart attack (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047), kidney disease (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as well as stomach disease (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) between the KOA and control groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Stomach disease was a risk factor for KOA\u003c/h2\u003e \u003cp\u003eThe relationship between stomach disease and KOA was explored by 3 weighted multivariate logistic regression models (\u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e), and model 1 (OR: 3.05, 95% CI: 1.75\u0026ndash;5.30) showed that stomach disease and KOA were significantly associated (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). After adjusting the location, gender and smoke, model 2 (OR: 3.02, 95% CI: 1.73\u0026ndash;5.28) revealed that stomach disease and KOA were apparent associated (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Based on model 2, after accounting for every covariate, the results of model 3 (OR: 2.48, 95% CI: 1.37\u0026ndash;4.47) clearly demonstrated a connection between stomach disease and KOA (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). Models 2 and 3 demonstrated that adding covariates did not change the stable relationship between stomach disease and KOA. Stomach disease is a risk factor for KOA. By performing a risk stratification analysis of the covariates in model 2, gender, location, as well as smoke were found to have no significant association with the risk of KOA, and there was a direct and significant association between stomach disease and KOA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). After considering for all covariates, risk stratification demonstrated that there was a significant and stable association between stomach disease and and KOA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThese results suggested that there was an obvious correlation between stomach disease and KOA, also stomach disease was a risk factor for KOA. Furthermore, the plotted ROC curves' area under the curve (AUC) values was 0.722, indicating that model 3 had high accuracy in predicting the risk of KOA, and that stomach disease showed good predictive value for changes in the risk of KOA (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eKOA is a prevalent degenerative joint disease, particularly affecting the elderly population[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Gastrointestinal diseases, including gastritis, peptic ulcers, and other gastrointestinal disorders, are also more common in the elderly[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Understanding the potential association between stomach diseases and knee osteoarthritis can provide valuable insights for prevention and treatment strategies. Our study suggested that there was an obvious and stable correlation between stomach disease and KOA, stomach disease was a risk factor for KOA. The findings encourage researchers and physicians to explore more effective therapies for KOA treatment.\u003c/p\u003e \u003cp\u003eMultiple personal habits, such as smoking, cardiovascular disease, and diabetes, were associated with an increased prevalence of OA and stomach problems[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e32\u003c/span\u003e], which are consistent with our findings. Our study revealed that the sleep duration of KOA group was noticeably shorter and showed significant differences in health status (P\u0026thinsp;=\u0026thinsp;0.014), heart attack (P\u0026thinsp;=\u0026thinsp;0.047), kidney disease (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as well as stomach disease (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) between the KOA and control groups. Studies show that poor sleep quality and insomnia are prevalent in older adults and are associated with increased risk of multiple health problems[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Moreover, sleep disturbance may further affect the health status of the elderly by activating inflammatory mechanisms [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Therefore, improving sleep quality may be an important strategy for the prevention and management of osteoarthritis and other related health problems. Yan Ren et al. found that the presence of heart disease, kidney disease, and digestive system diseases may be associated with a higher risk of developing symptomatic KOA [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Some scholars believe that KOA has an independent correlation with an increased risk of CVD (cardiovascular disease).[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e37\u003c/span\u003e] Diabetes and kidney diseases are associated with the symptom progression of knee OA [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e39\u003c/span\u003e]; there is a close correlation between smoking and the risk of knee osteoarthritis [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Even though our data shows an possible link between heart attack and osteoarthritis, till now, the detailed underling association is still not clear, the coincidence largely due to shared risk factors [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e35\u003c/span\u003e].In summary, poor lifestyle habits or having multiple chronic diseases simultaneously can both increase the risk of KOA.\u003c/p\u003e \u003cp\u003eEmerging research highlights that gastrointestinal disorders and osteoarthritis influence each other through several aspects, like the gut microbiota, gut-brain and gut-joint axis. Previous and our data showed a stable link between osteoarthritis and stomach diseases, the association may largely depend on the role of the gut microbiome and medication use[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Unhealthy gut microbiome healthy plays a key role in systemic inflammation, which allows inflammatory substances to enter the bloodstream, potentially exacerbating joint inflammation and contributing to OA progression[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Long-term use of high-dose NSAIDs of patients with osteoarthritis always may greatly increase the possibility of stomach diseases, and vice versa[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. If stomach diseases occur, the OA therapy needs to be changed, which results in additional treatment costs and causes discomfort for both patients and clinicians[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Therefore, it is necessary to create a stomach disease prediction model that can reflect the detailed health status of each individual and to use it when making treatment plans. Although there is a paucity of direct research investigating the acceleration of joint degeneration by inflammatory molecules entering the bloodstream in digestive system diseases, this association theoretically exists. Emerging research highlights that gastrointestinal disorders and osteoarthritis influence each other through several aspects, like the gut microbiota, gut-brain and gut-joint axis[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Stomach diseases and gut microbiota and are closely interconnected[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Disturbances in microbial balance can contribute to stomach diseases such as gastritis, peptic ulcers, gastro esophageal reflux disease (GERD), and even stomach cancer[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Yaqiong Zhou et al. found through a Mendelian randomization study that patients with GERD have a higher risk of developing KOA, which warrants our serious attention[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Gastric diseases can lead to nutritional absorption issues for patients, resulting in health problems such as weight loss [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. This subsequently affects the absorption of nutrients crucial for joint health, including calcium and vitamin D [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e51\u003c/span\u003e], thereby influencing the progression of KOA. These situations allow inflammatory molecules to enter the bloodstream[\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e53\u003c/span\u003e], thus may be accelerate joint degeneration. The gut-brain axis can affect pain pathways in OA through neuroinflammatory processes[\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Alterations in gut health may influence central pain processing, leading to heightened pain sensitivity or chronic pain conditions[55]. Long-term use of high-dose NSAIDs may greatly increase the possibility of gastric ulcers and reflux, disrupting the balances in the intestinal microbiome can elevate inflammation[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e56\u003c/span\u003e], complicating OA symptoms. This bidirectional relationship suggests the need for a balanced treatment strategy, focusing not only on joint management but also on stomach healthy. Therefore, it is necessary to create a stomach disease monitor model which can predict the occurrence of KOA and make more effective therapies.\u003c/p\u003e \u003cp\u003eThis study, for the first time, combines logistic regression modeling with risk stratification analysis to more precisely explore the complex relationship between gastric diseases and the risk of KOA. It fills a gap in the current literature regarding research on the association between gastric diseases and KOA risk, providing robust evidentiary support for a deeper understanding of the intrinsic connection between the two. This research holds significant guiding implications for future clinical practice and disease prevention. However, this study has a few limitations. First, we were unable to include enough OA patients to this study because of the database limitation, and could not engorge the bias caused by gender. Second, it was difficult to eliminate side effect of drugs, such as NSAIDs, aspirin, on the gastrointestinal mucosa, which certainly would increase the risk of stomach diseases, while these drugs could attenuate the symptoms of osteoarthritis, thus the data we obtained now could not support an accurate predictive model. Last, specific and accurate diagnose of stomach disease could only be obtained by gastric endoscopy and other clinical examines, and it was difficult to get reliably onset of stomach diseases because symptoms vary on the patient.\u003c/p\u003e \u003cp\u003eOur study explored the prevalence of stomach diseases in the general population and osteoarthritis patients, and has provided new evidence to support stomach diseases as a risk factor for osteoarthritis. This study contributes to a deeper understanding of the potential association between stomach diseases and osteoarthritis, providing new ideas and directions for clinical prevention and treatment of osteoarthritis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOsteoarthritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKOA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKnee osteoarthritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCHARLS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChina Health and Retirement Longitudinal Study\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReceiver operating characteristic\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCnfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAUC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAea under the curve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNSAIDs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNonsteroidal Anti-inflammatory Drugs\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePatelet-rich plasma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMenchymal stem cell\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGERD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGestro esophageal reflux disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCVD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCdiovascular disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all participants of the CHARLS and all workers who collected the data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. HL and PL had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. XY and XY contributed equally to this work. PL and HL wrote the manuscript. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Scientific Research Project of Chongqing Doctor Direct Train (CSTB2022BSXM-JCX0084), Doctoral research start‐up fund of Chongqing University Three Gorges Hospital (ZX-50010101-2022-285) and Natural Science Foundation of Guangdong Province (2023A1515011572).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data collected in the CHARLS are maintained at the National School of Development of Peking University, Beijing, China. The datasets are available from http://charls.pku.edu.cn/pages/data/111/zh-cn.html.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe current study is a secondary analysis of the CHARLS public data. No separate ethical approval was required for our study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The original CHARLS was approved by the Ethical Review Committee of Peking University, and all participants signed informed consent at the time of participation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFerrari AJ, Santomauro DF, Aali A, Abate YH, Abbafati C, Abbastabar H, Abd ElHafeez S, Abdelmasseh M, Abd-Elsalam S, Abdollahi A, et al. 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Front Cell Infect Microbiol 2022, 12.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Stomach disease, Knee osteoarthritis, CHARLS, Logistic regression models, Receiver operating characteristic","lastPublishedDoi":"10.21203/rs.3.rs-5364266/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5364266/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe knee joint is one of the most frequently affected joints in osteoarthritis (OA). However, the specific connection between gastric diseases and the occurrence of knee osteoarthritis (KOA) is currently unclear. The objective of this study is to explore the potential association between gastric diseases and KOA using the China Health and Retirement Longitudinal Study (CHARLS) database.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 1053 subjects with complete information in 2018 from CHARLS database were included. First, the baseline characteristics of these subjects (covariates such as gender, residence, and smoke) were compared. Then, the relationship between stomach diseases and KOA was explored through 3 weighted multivariate logistic regression models. Afterwards, risk stratification analyses were taken to further confirm the stability of the correlation between stomach disease and KOA risk in different populations. The receiver operating characteristic (ROC) curve of model 3 was plotted to verify the predictive efficiency of stomach disease in KOA risk.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ewe divided the subjects into 2 groups: the KOA group (n\u0026thinsp;=\u0026thinsp;71) and the control group (n\u0026thinsp;=\u0026thinsp;982). The baseline characteristics table revealed that substantial differences in heart attack, kidney illness, stomach disease, as well as health status between the KOA and control groups. Model 1 had an odds ratio (OR) of 3.05 (95% confidence interval (CI)\u0026thinsp;=\u0026thinsp;1.75\u0026ndash;5.30, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After adjusting for location, gender, and smoke, model 2's OR was 3.02 (95% CI\u0026thinsp;=\u0026thinsp;1.73\u0026ndash;5.28, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while model 3's OR was 2.48 (95% CI\u0026thinsp;=\u0026thinsp;1.37\u0026ndash;4.47, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). The 3 models demonstrated that stomach disease and KOA were significantly associated and stomach disease was a risk factor for KOA, and the other covariates did not change the relationship. Risk stratification analyses indicated a stable association between stomach disease and KOA risk across populations. The area under the curve (AUC) was 0.722, indicating that model 3 had a good predictive accuracy.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn this study, we furtherly explored the correlation between stomach disease and KOA, and certified that stomach disease was a risk factor for KOA, which provided a reference for the correlation analysis between them.\u003c/p\u003e","manuscriptTitle":"Unveiling the Hidden Link: Stomach Disease as a Risk Factor for Knee Osteoarthritis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-14 13:41:15","doi":"10.21203/rs.3.rs-5364266/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9dcf5476-dade-4518-a0eb-95ebfa96b2d9","owner":[],"postedDate":"November 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-08T06:56:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-14 13:41:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5364266","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5364266","identity":"rs-5364266","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}