Associations between osteoarthritis and comorbidities before and after diagnosis across four European primary care databases: a multinational case-control and cohort study.

Background: Osteoarthritis (OA) is associated with some comorbidities. However, the consistency of the associations across different countries is unclear. We analysed relationships between OA and 61 comorbidities before and after diagnosis using data from four European primary care databases: the UK, the Netherlands, Sweden, and Spain. Methods: The multinational ComOA study combined case-control and cohort designs in people aged ≥18 years using large primary care records databases in each country. The study population consisted of incident OA cases, and age and sex matched controls without OA. We reported adjusted odds ratios (aOR) and adjusted hazard ratios (aHR) after adjusting for other covariates. Pooled proportions with comorbidities, ORs and HRs were estimated using random effect methods for congruency evidence. Congruency was present if the results of all the countries favoured in one direction. Findings: The four databases included 845,373 OA cases and 2,556,243 matched controls combined for prospective and retrospective studies. The percentage of women varied from 41.7% (808,725/1,936,792) in Spain to 64.0% (254,930/398,143) in the Netherlands. Mean age at diagnosis of OA was lowest in the UK (59.8 years, SD 12.8), and highest in the Netherlands (65.8 years, SD 12.2). Retrospectively, 10 out of 33 comorbidities studied by all four countries showed congruent associations with OA such as, fibromyalgia (aOR 1.93; 95% CI 1.49-2.49), polymyalgia rheumatica (aOR 1.44; 95% CI 1.31-1.58), and chronic back pain (aOR 1.42; 95% CI 1.32-1.53). Prospectively, three of eight conditions studied by all four countries showed congruent, i.e., depression (aHR 1.11; 95% CI 1.07-1.16), osteoporosis (aHR 1.05; 95% CI 1.01-1.09), and hypertension (aHR 1.05; 95% CI 1.02-1.09). Additionally, contingency was also observed between retrospective and prospective studies for sleep problem, migraine, asthma, eczema, and benign prostatic hypertrophy. Interpretation: OA is associated with some long-term conditions across Europe, despite different population structures and health systems. Further research is needed to understand the mechanisms shared between OA and comorbidities for these associations, especially those congruent across nations. Funding: This work was supported by Foundation for Research in Rheumatology (FOREUM) grant The Swedish Research Council, Governmental funding of clinical research within the national health services (ALF), and The Swedish Rheumatism Association. CM is funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West Midlands, the National Institute for Health Research (NIHR) School for Primary Care Research and a National Institute for Health Research (NIHR) Research Professorship in General Practice.