Comorbidities in Osteoarthritis


Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability in older people. The prevalence of OA increases in the past 20 years(1). However, little has been done into its burden such as comorbidities. Our recent systematic review has found that people with OA are more likely to have other diseases, especially stroke, peptic ulcer, hypertension and depression(2).  Whether these comorbidities just co-exist with, share common risk factors with or are causes or consequences of OA remains unknown. 

Facts and Figures

Project Lead
W Zhang
University of Nottingham
FOREUM research grant: € 600.000

Meet the Team

Project Lead

W Zhang
University of Nottingham
C Coupland
University of Nottingham
S Swain
University of Nottingham
S Bierma-Zeinstra
Erasmus MC Netherlands
J Runhaar
Erasmus MC Netherlands
A Kamps
Erasmus MC Netherlands
M Englund
Lund University
A Turkiewicz
Lund University
A Dell'isola
Lund University
D Prieto-Alhambra
Autonomous University of Barcelona
D Robinson
Autonomous University of Barcelona
A Vivekanantham
Autonomous University of Barcelona
M Far Ruiz
Autonomous University of Barcelona
I Pitsillidou
S Vanhegan
J Cockshull


This project aims to examine:

  • prevalence, incidence and associations and time sequence of comorbidities in OA;
  • common clusters and impact of comorbidities on patient health  states;
  • association between commonly used OA drugs such as non-steroidal anti-inflammatory (NSAIDs) and comorbidities;
  • early biomarkers and mechanistic pathways between OA and the comorbidities; 
  • consistency of OA comorbidities and clusters across countries.

Five work packages (WP) will be performed for these  five objectives.  Four national registration databases in the UK, Netherlands, Sweden and Spain will be used for WP1-3.  Two cohort study databases (the UK Biobank and the Rotterdam study) will be used for WP4.  Finally, data from different countries will be meta-analysed (WP5) to examine the consistency between countries and to pool results together as appropriate.  

So far, UK and Sweden have been able to produce some results on the comorbidities associated with OA.

Swedish database studied the association with 18 conditions. UK database examined the association with 49 conditions before and after the diagnosis of OA. Besides, the clusters of comorbidities were explored among OA and matched controls using UK database.


Months 0-6: data extraction, cohort development, case/control matching, data cleaning, coding and validation
Months 7-24: complete WP1-3
Months 25-36:  complete WP4-5

Interim Results

In Sweden, people with physician-diagnosed knee or hip OA were more likely to develop depression, cardiovascular diseases, back pain, and osteoporosis than people without OA.

In the UK, people with physician diagnosed OA were more likely to develop multimorbidity (≥2 other diseases).  The hazard ratio was 1.34, (95% CI 1.82-1.41) between OA and non-OA after adjusting for age, gender, BMI, smoking status and alcohol consumption.

Leading comorbidities were fibromyalgia, rheumatoid arthritis, liver diseases, sleep problems, ankylosing spondylitis, dementia, heart failure, osteoporosis, anaemia, and peripheral vascular diseases. In the OA group five clusters were identified including relatively healthy (18%), ‘cardiovascular/musculoskeletal ’ (12.3%), metabolic syndrome (28.2%), ‘pain and psychological (9.1%), and ‘musculoskeletal’ (32.4%). The non-OA group had similar patterns except that the ‘pain+ psychological’ cluster was replaced by ‘thyroid and psychological’.


  • S. Swain, C. Coupland, C. Mallen, CF. Kuo, A. Sarmanova, S.M.A. Bierma-Zeinstra, M. Englund, D. Prieto-Alhambra, M. Doherty, W. Zhang. Temporal relationship between osteoarthritis and comorbidities: a combined case control and cohort study in the UK primary care setting. Rheumatology, Volume 60, Issue 9, September 2021, Pages 4327–4339,
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  • A. Dell'Isola, K. Pihl, A. Turkiewicz, V. Hughes, W. Zhang, S. Bierma-Zeinstra, D. Prieto-Alhambra, M. Englund. Risk of comorbidities following physician-diagnosed knee or hip osteoarthritis: a register-based cohort study. Arthritis Care Res (Hoboken). 2021 Jun 4. doi: 10.1002/acr.24717. Epub ahead of print. PMID: 34086422.
    Read more
  • A. Dell’Isola, A.Turkiewicz, W. Zhang, A. Kiadaliri, S. Bierma-Zeinstra, J. Runhaar, D. Prieto-Alhambra, M. Englund. Does osteoarthritis modify the association between NSAID use and risk of comorbidities and adverse events?, Osteoarthritis and Cartilage Open, Volume 4, Issue 2, 2022, 100253, ISSN 2665-9131
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  • S. Swain, C. Coupland, V. Strauss, C. Mallen, C.F. Kuo, A. Sarmanova, S.M.A. Bierma-Zeinstra, M. Englund, D. Prieto-Alhambra, M. Doherty, W. Zhang, Clustering of comorbidities and associated outcomes in people with osteoarthritis - A UK Clinical Practice Research Datalink study, Osteoarthritis and Cartilage, 2022, ISSN 1063-4584
    Read more

Conference Papers

  • Andrea Dell’Isola, Aleksandra Turkiewicz, Subhashisa Swain, Weiya Zhang, Sita Bierma-Zeinstra, Jos Runhaar, Daniel Prieto-Alhambra, Martin Englund, The association between different comorbidities and osteoarthritis development in peripheral joints: a population based nested case-control study. (OARSI 2022)
  • A. Kamps, J. Runhaar, M. de Wilde, M.A.J. de Ridder, J. van der Lei, S. Swain, W. Zhang, D. Prieto-Alhambra, M. Englund, E.I.T de Schepper, S.M.A. Bierma-Zeinstra. Prevalence of comorbidity among incident osteoarthritis patients and matched controls”. (Orally presented at NAPCRG 2021 & OARSI 2022)
  • Pineda Moncusi M.; Strauss, V.; Robinson, D.; Prieto-Alhambra, D. and Khalid, S. (2022). Unsupervised Learning to Understand Patterns of Comorbidity in 633,330 Patients Diagnosed with Osteoarthritis. In Proceedings of the 15th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, ISBN 978-989-758-552-4, ISSN 2184-4305, pages 121-129. (BIOSTEC 2022)
  • Pineda Moncusi M.; Strauss, V.; Robinson, D.; Prieto-Alhambra, D. and Khalid, S. (2022). Unsupervised Learning to Understand Patterns of Comorbidity in 633,330 Patients Diagnosed with Osteoarthritis. BIOINFORMATICS - 13th International Conference on Bioinformatics Models, Methods and Algorithms. Oral Communication #10 (Feb 12th 2022). (BSM, 2022)

EULAR Abstracts


  • OPO184: Risk of comorbidities following incident clinician-diagnosed knee or hip osteoarthritis: a registry-based cohort study.
    K. Pihl, A. Turkiewicz, V. Hughes, W. Zhang, S. M. A. Bierma-Zeinstra, D. Prieto-Alhambra, M. Englund.
  • OPO074: Multimorbidity clusters, determinants and trajectories in Osteoarthritis in the UK: findings from the Clinical Practice Research Datalink
    S. Swain , C. Coupland , V. Strauss , C. Mallen , C. F. Kuo , A. Sarmanova , M.Doherty , W. Zhang.

Go to EULAR Abstract Archive

Patient Voice

Three patient research partners (PRPs) are involved in the project since we applied for this project. They have actively participated in the meetings and shared their views on the list of conditions to be studied, possible ways of disseminations and the challenges they face because of the comorbidities.

Project Map