Risk factors for the development of knee osteoarthritis across the lifespan: a systematic review and meta-analysis

Duong V 1 , Shaheed CA 2 , Ferreira ML 3 , Narayan SW 4 , Venkatesha V 5 , Hunter DJ 6 Show all authors , Zhu J 7 , Atukorala I 8 , Kobayashi S 9 , Goh SL 10 , Briggs AM 11 , Cross M 9 , Espinosa-Morales R 12 , Fu K 13 , Guillemin F 14 , Keefe F 15 , Stefan Lohmander L 16 , March L 6 , Milne GJ 17 , Mei Y 18 , Mobasheri A 19 , Namane M 20 , Peat G 21 , Risberg MA 22 , Sharma S 23 , Sit R 24 , Telles RW 25 , Zhang Y 26 , Cooper C 27

Affiliations 

  • 1 Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, New South Wales, Sydney Australia. Electronic address: vicky.duong@sydney.edu.au
  • 2 Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, New South Wales, Sydney Australia; Faculty of Medicine and Health, School of Public Health, University of Sydney, Sydney, New South Wales, Australia. Electronic address: christina.abdelshaheed@sydney.edu.au
  • 3 Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, New South Wales, Sydney Australia; The George Institute for Global Health, Faculty of Medicine and Health, The University of New South Wales, Sydney, New South Wales, Australia
  • 4 Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, New South Wales, Sydney Australia; Faculty of Medicine and Health, School of Public Health, University of Sydney, Sydney, New South Wales, Australia
  • 5 Northern Sydney Local Health District Executive, Royal North Shore Hospital, Sydney, New South Wales Australia; Faculty of Medicine and Health, School of Public Health, University of Sydney, Sydney, New South Wales, Australia
  • 6 Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, New South Wales, Sydney Australia; Rheumatology Department, Royal North Shore Hospital, Sydney, New South Wales, Australia
  • 7 Rheumatology Department, Royal North Shore Hospital, Sydney, New South Wales, Australia; Liverpool Hospital, Sydney, New South Wales, Australia
  • 8 Department of Clinical Medicine, University of Colombo, Sri Lanka
  • 9 Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, New South Wales, Sydney Australia
  • 10 Centre for Epidemiology and Evidence-Based Practice, Universiti Malaya, Kuala Lumpur, Malaysia; Sports and Exercise Medicine Research and Education Group, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
  • 11 Curtin School of Allied Health, Curtin University, Perth, Western Australia, Australia
  • 12 National Institute of Rehabilitation, National University Autonomous of Mexico, Mexico
  • 13 Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 14 Université de Lorraine, Inserm, INSPIIRE, Nancy, France
  • 15 Duke Pain Prevention and Treatment Research Program, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina, USA
  • 16 Department of Clinical Sciences Lund, Orthopedics, Lund University, Sweden
  • 17 Marshall Centre for Infectious Disease Research and Department of Computer Science and Software Engineering, University of Western Australia, Western Australia, Australia
  • 18 Department of Rheumatology and Immunology, The Second Affiliated Hospital of Southern University of Science and Technology/The Third People's Hospital of Shenzhen, Shenzhen, China
  • 19 Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania; Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, Liège, Belgium
  • 20 Division of Family Medicine, Department of Family, Community and Emergency Medicine, University of Cape Town, South Africa
  • 21 Centre for Applied Health & Social Care Research (CARe), Sheffield Hallam University, United Kingdom
  • 22 Department of Sport Medicine, Norwegian School Sport Sciences and Division of Orthopaedic Surgery, Oslo University Hospital, Norway
  • 23 Pain Management and Research Centre, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, Australia; School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia
  • 24 The Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong
  • 25 Department of Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Rheumatology Service, Hospital das Clínicas da UFMG/Ebserh, Belo Horizonte, Brazil
  • 26 Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • 27 University of Southampton, United Kingdom; and Institute of Musculoskeletal Science; University of Oxford, Oxfordshire, United Kingdom
Osteoarthritis Cartilage, 2025 Mar 31.
PMID: 40174718 DOI: 10.1016/j.joca.2025.03.003

Abstract

OBJECTIVE: To identify and quantify risk factors for incident knee osteoarthritis (KOA) across the lifespan.

METHODS: This systematic review and meta-analysis identified eligible studies from seven electronic databases and three registries. Longitudinal cohort studies or randomised controlled trials evaluating participants who developed incident symptomatic and/or radiographic KOA were included. Two independent reviewers completed data screening and extraction. Estimates were pooled using a random effects model and reported as odds ratio (OR), hazard ratio (HR), or risk ratio (RR) and corresponding 95% confidence intervals (95% CI). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to determine the certainty of evidence. Population attributable fractions (PAFs) were calculated, including risk factors significantly associated with radiographic KOA based on the pooled meta-analysis and where we could determine communality scores using existing clinical datasets.

RESULTS: We identified 132 studies evaluating >150 risk factors. Higher body mass index (BMI), previous knee injury, older age and high bone mineral density were associated with an increased risk of incident radiographic KOA based on the pooled analysis [OR (95% CI): 1.56 (1.25, 1.95), 3.02 (1.93, 4.71), 1.15 (1.00, 1.33) and 1.82 (1.12, 2.94), respectively], with moderate-to-high certainty. Two risk factors (overweight/obesity and previous knee injury) accounted for 14% of incident radiographic KOA. Other modifiable risk factors including occupational physical activity also contribute to radiographic or symptomatic KOA.

CONCLUSION: Novel strategies addressing known modifiable risk factors including overweight/obesity, knee injuries and occupational physical activity are needed to reduce overall burden of KOA.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID: CRD42023391187 FUNDING: Sydney Musculoskeletal Health, Faculty of Medicine and Health, The University of Sydney.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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