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Mechanical contributors to sex differences in idiopathic knee osteoarthritis

Daniel P Nicolella12*, Mary I O’Connor13, Roger M Enoka14, Barbara D Boyan15, David A Hart16, Eileen Resnick1, Karen J Berkley17, Kathleen A Sluka18, C Kent Kwoh19, Laura L Tosi110, Richard D Coutts111, Lorena M Havill112 and Wendy M Kohrt113

Author Affiliations

1 Isis Research Network on Musculoskeletal Health, Society for Women’s Health Research, Washington, DC, 20036, USA

2 Mechanical Engineering Division, Southwest Research Institute, San Antonio, TX, 78238, USA

3 Department of Orthopedic Surgery, Mayo Clinic, Jacksonville, FL, 32224, USA

4 Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, 80309, USA

5 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA

6 Department of Surgery, University of Calgary, Calgary, AB, T2N 4N1, Canada

7 Program of Neuroscience, Florida State University, Tallahassee, FL, 32306, USA

8 Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, 52242, USA

9 Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, 15261, USA

10 Department of Orthopedic Surgery and Pediatrics, George Washington University, Washington, DC, 20010, USA

11 Department of Orthopedic Surgery, University of California, San Diego, San Diego, CA, 92123, USA

12 Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, 78245, USA

13 Division of Geriatric Medicine, University of Colorado Denver, Aurora, CO, 80045, USA

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Biology of Sex Differences 2012, 3:28  doi:10.1186/2042-6410-3-28

Published: 23 December 2012


The occurrence of knee osteoarthritis (OA) increases with age and is more common in women compared with men, especially after the age of 50 years. Recent work suggests that contact stress in the knee cartilage is a significant predictor of the risk for developing knee OA. Significant gaps in knowledge remain, however, as to how changes in musculoskeletal traits disturb the normal mechanical environment of the knee and contribute to sex differences in the initiation and progression of idiopathic knee OA. To illustrate this knowledge deficit, we summarize what is known about the influence of limb alignment, muscle function, and obesity on sex differences in knee OA. Observational data suggest that limb alignment can predict the development of radiographic signs of knee OA, potentially due to increased stresses and strains within the joint. However, these data do not indicate how limb alignment could contribute to sex differences in either the development or worsening of knee OA. Similarly, the strength of the knee extensor muscles is compromised in women who develop radiographic and symptomatic signs of knee OA, but the extent to which the decline in muscle function precedes the development of the disease is uncertain. Even less is known about how changes in muscle function might contribute to the worsening of knee OA. Conversely, obesity is a stronger predictor of developing knee OA symptoms in women than in men. The influence of obesity on developing knee OA symptoms is not associated with deviation in limb alignment, but BMI predicts the worsening of the symptoms only in individuals with neutral and valgus (knock-kneed) knees. It is more likely, however, that obesity modulates OA through a combination of systemic effects, particularly an increase in inflammatory cytokines, and mechanical factors within the joint. The absence of strong associations of these surrogate measures of the mechanical environment in the knee joint with sex differences in the development and progression of knee OA suggests that a more multifactorial and integrative approach in the study of this disease is needed. We identify gaps in knowledge related to mechanical influences on the sex differences in knee OA.

Knee joint; Limb alignment; Muscle function; Obesity; Osteoarthritis; Sex differences