Sex differences in musculoskeletal injury and disease risks across the lifespan: Are there unique subsets of females at higher risk than males for these conditions at distinct stages of the life cycle?

Abstract

Sex differences have been reported for diseases of the musculoskeletal system (MSK) as well as the risk for injuries to tissues of the MSK system. For females, some of these occur prior to the onset of puberty, following the onset of puberty, and following the onset of menopause. Therefore, they can occur across the lifespan. While some conditions are related to immune dysfunction, others are associated with specific tissues of the MSK more directly. Based on this life spectrum of sex differences in both risk for injury and onset of diseases, a role for sex hormones in the initiation and progression of this risk is somewhat variable. Sex hormone receptor expression and functioning can also vary with life events such as the menstrual cycle in females, with different tissues being affected. Furthermore, some sex hormone receptors can affect gene expression independent of sex hormones and some transitional events such as puberty are accompanied by epigenetic alterations that can further lead to sex differences in MSK gene regulation. Some of the sex differences in injury risk and the post-menopausal disease risk may be “imprinted” in the genomes of females and males during development and sex hormones and their consequences only modulators of such risks later in life as the sex hormone milieu changes. The purpose of this review is to discuss some of the relevant conditions associated with sex differences in risks for loss of MSK tissue integrity across the lifespan, and further discuss several of the implications of their variable relationship with sex hormones, their receptors and life events.

Inhibition of focal adhesion kinase 2 results in a macrophage polarization shift to M2 which attenuates local and systemic inflammation and reduces heterotopic ossification after polysystem extremity trauma

“…Notably, acute inflammatory responses differ between male and female rats, as well as in humans. Prior reports have shown that males are more susceptible to traumatic injury ( 94 , 95 ). However, the utilization of only male rats in this study is justified, considering that fewer than 3% of severely combat-injured service members in recent conflicts were female ( 96 ).…”

γ-Aminobutyric acids (GABA) and serum GABA/AABA (G/A) ratio as potential biomarkers of physical performance and aging

“…The short Form-36 Physical Functioning Scale (SF36 PFS) questionnaire is a set of patient self-reporting measures to indicate health status. The SF-36 PFS is composed of 10 items encompassing a hierarchical range of difficulties on everyday activities, including vigorous activities, moderate activities, lifting/carrying, climbing stairs, bending/kneeling/stooping, and walking, etc., and it has been used as a reliable and valid “stand-alone” instrument in research describing activity limitations in the elderly living in the community, and patients with different minor pathophysiological conditions and chronic diseases 39 – 41 . These results strongly suggest that G/A ratio could be a potential circulating biomarker to indicate change in physical performance, particularly mobility performance in males.…”

The impact of COVID-19 related lockdown restrictions on musculoskeletal health: a systematic review

“…The sex difference pattern in COVID-19 related MSK disorders observed in this review is consistent with earlier submissions. Specifically, Hart [ 36 ] suggests that the higher risk for injuries to tissues of the MSK system in females is attributable to hormonal changes across lifespan, but markedly at onsets of puberty and menopause; gene expression independent of sex hormones; and immune dysfunction. In line with the foregoing, Wolf et al [ 37 ] conclude that structural anatomy differences, hormones, and genetics are important considerations in sex difference in MSK disorders between males and females.…”