Unraveling sex-specific risks of knee osteoarthritis before menopause: Do sex differences start early in life?

Paula A Hernandez; John Churchill Bradford; Priyanka Brahmachary; Sophia Ulman; Jennifer L Robinson; Ronald K June; Magali Cucchiarini

doi:10.1016/j.joca.2024.04.015

Unraveling sex-specific risks of knee osteoarthritis before menopause: Do sex differences start early in life?

Osteoarthritis Cartilage. 2024 May 2:S1063-4584(24)01172-5. doi: 10.1016/j.joca.2024.04.015. Online ahead of print.

Authors

Paula A Hernandez¹, John Churchill Bradford², Priyanka Brahmachary³, Sophia Ulman⁴, Jennifer L Robinson⁵, Ronald K June⁶, Magali Cucchiarini⁷

Affiliations

¹ Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Department of Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: Paula.Hernandez2@utsouthwestern.edu.
² Department of Bioengineering, University of Washington, Seattle, WA 98195, USA. Electronic address: jcb207@uw.edu.
³ Department of Mechanical & Industrial Engineering, Montana State University, Bozeman, MT 59717, USA. Electronic address: Priyanka.Brahmachary@montana.edu.
⁴ Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Movement Science Laboratory, Scottish Rite for Children, Frisco, TX 75034, USA. Electronic address: Sophia.Ulman@tsrh.org.
⁵ Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA; Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA. Electronic address: jrobins1@uw.edu.
⁶ Department of Mechanical & Industrial Engineering, Montana State University, Bozeman, MT 59717, USA. Electronic address: rjune@montana.edu.
⁷ Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg/Saar D-66421, Germany. Electronic address: mmcucchiarini@hotmail.com.

PMID: 38703811
DOI: 10.1016/j.joca.2024.04.015

Abstract

Objective: Sufficient evidence within the past two decades have shown that osteoarthritis (OA) has a sex-specific component. However, efforts to reveal the biological causes of this disparity have emerged more gradually. In this narrative review, we discuss anatomical differences within the knee, incidence of injuries in youth sports, and metabolic factors that present early in life (childhood and early adulthood) that can contribute to a higher risk of OA in females.

Design: We compiled clinical data from multiple tissues within the knee joint-since OA is a whole joint disorder-aiming to reveal relevant factors behind the sex differences from different perspectives.

Results: The data gathered in this review indicate that sex differences in articular cartilage, meniscus, and anterior cruciate ligament are detected as early as childhood and are not only explained by sex hormones. Aiming to unveil the biological causes of the uneven sex-specific risks for knee OA, we review the current knowledge of sex differences mostly in young, but also including old populations, from the perspective of (i) human anatomy in both healthy and pathological conditions, (ii) physical activity and response to injury, and (iii) metabolic signatures.

Conclusions: We propose that to close the gap in health disparities, and specifically regarding OA, we should address sex-specific anatomic, biologic, and metabolic factors at early stages in life, as a way to prevent the higher severity and incidence of OA in women later in life.

Keywords: Anterior cruciate ligament; Cartilage; Estrogen; Meniscus; Metabolomics; Sex differences.

Publication types

Review