Hospital-Treated Infections and 15-year Incidence of Musculoskeletal Disorders: A Large Population-Based Cohort Study

Yaqing Gao,1 Dylan McGagh,2 Lei Ding,3 Shenda Hong,4,5 Zhengxiao Ouyang,6 Jie Wei,7– 10 Chao Zeng,7– 10 Guanghua Lei,7– 10 Junqing Xie2,7 1Nuffield Department of Population Health, University of Oxford, Oxford, UK; 2Centre for Statistics in Medicine and NIHR Biomedical Research Centre Oxford, NDORMS, University of Oxford, Oxford, UK; 3State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4National Institute of Health Data Science, Peking University, Beijing, People’s Republic of China; 5Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China; 6Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 7Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 8Key Laboratory of Aging-Related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 9Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 10National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Guanghua Lei, Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China, Email [email protected] Junqing Xie, Centre for Statistics in Medicine and NIHR Biomedical Research Centre Oxford, NDORMS, University of Oxford, Oxford, Oxfordshire, OX3 7LD, UK, Tel +44 1865 227374, Email [email protected]: Basic science evidence reveals interactions between the immune and bone systems. However, population studies linking infectious diseases and musculoskeletal (MSK) disorders are limited and inconsistent. We aimed to examine the risk of six main MSK disorders (osteoarthritis, rheumatoid arthritis, osteoporosis, gout, low back pain, and neck pain) following hospital-treated infections in a large cohort with long follow-up periods.Methods: We analysed data from 502,409 UK Biobank participants. Participants free of specific MSK disorders at baseline were included in each analysis. Hospital-treated infections before baseline were identified using national inpatient data, while incident MSK outcomes were ascertained from inpatient records, primary care, and death registers. Participants with prior infections were propensity score matched (1:5) with those without. Hazard ratios (HRs) and absolute rate differences (ARDs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. To assess potential reverse causality due to delayed diagnosis of preexisting illness, analyses were repeated excluding MSK disorder cases that occurred within the first 5 and 10 years post-baseline.Results: A hospital-treated infection was associated with increased risks of all six MSK disorders, with particularly strong associations for osteoporosis (HR, 1.55 [1.48– 1.63]; ARD, 1.48 [95% CI 1.29– 1.68] per 1000 person-years) and rheumatoid arthritis (HR, 1.53 [1.41– 1.65]; ARD, 0.58 [0.46– 0.71] per 1000 person-years), while other disorders showed HRs of 1.28– 1.32. Bacterial and viral infections showed similar associations, with MSK infections (generally stronger risk) and other locations both linked to increased risks. Associations remained significant even for incident cases that occurred more than 10 years post-baseline.Conclusion: Hospital-treated infections are associated with long-term MSK disorder risks, regardless of pathogen type or disorder nature (inflammatory or degenerative). Long-term monitoring and care for MSK health in patients with prior hospital-treated infections are recommended.Plain Language Summary: Recent studies have revealed intimate interactions between immune and bone cells. However, population studies on the link between infection and musculoskeletal (MSK) disorders are limited. In this large-scale study with balanced covariates and over 15 years of follow-up, we found that people who had hospital-treated infections had a higher risk of developing MSK conditions, including those related to bone metabolism (osteoporosis), inflammation (eg, rheumatoid arthritis, gout), and degenerative processes (eg, osteoarthritis). This increased risk was not specific to a particular infection and grew with more frequent and severe infections, suggesting a systemic rather than pathogen-specific effect. The risk persists beyond 10 years, highlighting the need for long-term MSK care for individuals with a history of severe infections.Keywords: infectious disease, osteoarthritis, rheumatoid arthritis, osteoporosis, gout, low back pain