Modern-day environmental factors in the pathogenesis of osteoarthritis


The prevalence of osteoarthritis (OA) is rising for reasons that are not fully understood. In this Opinion article, we review the possibility that OA is an evolutionary mismatch disease, which is a disease more common today than in the past because genes inherited from previous generations are inadequately or imperfectly adapted to modern environmental conditions. We focus on four major environmental factors in OA pathogenesis that have become ubiquitous within the past half-century: obesity, metabolic syndrome, dietary changes and physical inactivity. Because a cure for OA does not yet exist, prevention strategies that target these modifiable environmental factors are needed to curb further increases in OA prevalence.

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Fig. 1: Model of osteoarthritis as a mismatch disease.
Fig. 2: Mechaflammation versus metaflammation.
Fig. 3: Diet as a mismatch factor.
Fig. 4: Physical inactivity as a mismatch factor.


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The work of the authors is financially supported by grants from the French Society of Rheumatology, Fondation Arthritis (ROAD network) (to F.B.), the Hintze Family Charitable Foundation, the American School of Prehistoric Research (Harvard University) (to D.E.L.) and a grant from the US National Institutes of Health (AR47785 to D.T.F.).

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A phenotypic trait favoured by natural selection because it improves an organism’s ability to survive and reproduce.

Developed nations

Wealthy countries with post-industrial economies and advanced technological infrastructure.


People who subsist on foraged wild plants and hunted wild animals, in contrast to agriculturalists who subsist mainly on domesticated plants and animals.

Knee adduction moments

Dynamic rotational forces (torques) that act on the knee in the coronal plane, applying a compressive force to the medial side of the knee.

Kellgren−Lawrence score

A common method of classifying the severity of knee osteoarthritis using radiography.


Focal inflammation owing to a local mechanical insult.


Chronic, low-grade, metabolic and systemic inflammation.

Varus malalignment

A deformity of the knee in which the distal leg is angled medially in relation to the axis of the thigh, resulting in a bowlegged appearance.

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Berenbaum, F., Wallace, I.J., Lieberman, D.E. et al. Modern-day environmental factors in the pathogenesis of osteoarthritis. Nat Rev Rheumatol 14, 674–681 (2018). https://doi.org/10.1038/s41584-018-0073-x

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