Understanding the Observed Sex Discrepancy in the Prevalence of Osteoarthritis

Ferre, Isabella M; Roof, Mackenzie A.; Anoushiravani, Afshin A.; Wasterlain, Amy S.; Lajam, Claudette M.

doi:10.2106/jbjs.rvw.18.00182

Cited by 18 publications

(21 citation statements)

References 103 publications

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“…With regard to the incidence based on sex, in the general population the prevalence of OA adjusted for age is higher in women than in men. 32,33 Interestingly, our systematic review showed that, among the physically active population, the prevalence of OA is higher in males. This could be explained by the fact that males undertake more intense sporting activities than women, exposing the body and joints to greater stresses and loads.…”

Section: Discussionmentioning

confidence: 91%

The Association Between Sex and Osteoarthritis in the Physically Active Population: A Systematic Review

Migliorini

Torsiello

Padula

et al. 2022

Sports Medicine and Arthroscopy Review

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Purpose: Intense sporting activity and certain types of work increase the risk of early osteoarthritis (OA). OA can be idiopathic or associated to certain predisposing factors: female sex, obesity, history of joint injury, and joint overuse. The role of gender among the active population as a predisposing factor for OA is not well clear. This study investigated whether the risk of OA changes with age in both sexes in physically active individuals.Materials and Methods: This systematic review was conducted according to the PRISMA guidelines 2020. PubMed, Google Scholar, Embase, and Web of Science databases were accessed in April 2021. No time constrains were used for the search. All the published clinical studies reporting data about relationship between physical activity and OA were included.Results: Data from 7 articles were retrieved including 360,053 patients (271,903 males; 88,150 females). The mean age was 48.2 ± 16.7 years. Males, under the age of 60 had a higher risk of developing OA. People undertaking intense physical activity, such as professional athletes or heavy workers, are more prone to develop early OA. Conclusion:Physically active males demonstrated a higher risk of developing OA.

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Section: Discussionmentioning

confidence: 91%

The Association Between Sex and Osteoarthritis in the Physically Active Population: A Systematic Review

Migliorini

Torsiello

Padula

et al. 2022

Sports Medicine and Arthroscopy Review

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“…The cellular and molecular mechanisms behind the well-documented sex discrepancy in OA incident rates are poorly understood. Many factors are believed to contribute to the higher incidence and severity of OA in females, such as age, psychosocial status, metabolic variables, hormonal differences, anatomical variations, and inflammatory disease ( Ferre et al, 2019 ). While the focus of many previous studies was mainly on bone shape ( Yang et al, 2014 ; Wise et al, 2016 ; Frysz et al, 2020 ), gait kinematics ( Phinyomark et al, 2016 ; Ro et al, 2017 ; Allison et al, 2018 ), and sex hormones ( Zazulak et al, 2006 ; Brennan et al, 2010 ; Boyan et al, 2013b ; Wang et al, 2013 ; Antony et al, 2016 ), little effort was invested into determining differences in the global transcriptome profile.…”

Section: Discussionmentioning

confidence: 99%

Engineered Human Meniscus in Modeling Sex Differences of Knee Osteoarthritis in Vitro

Kunze

et al. 2022

Front. Bioeng. Biotechnol.

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Background: Osteoarthritis (OA) primarily affects mechanical load-bearing joints. The knee joint is the most impacted by OA. Knee OA (KOA) occurs in almost all demographic groups, but the prevalence and severity are disproportionately higher in females. The molecular mechanism underlying the pathogenesis and progression of KOA is unknown. The molecular basis of biological sex matters of KOA is not fully understood. Mechanical stimulation plays a vital role in modulating OA-related responses of load-bearing tissues. Mechanical unloading by simulated microgravity (SMG) induced OA-like gene expression in engineered cartilage, while mechanical loading by cyclic hydrostatic pressure (CHP), on the other hand, exerted a pro-chondrogenic effect. This study aimed to evaluate the effects of mechanical loading and unloading via CHP and SMG, respectively, on the OA-related profile changes of engineered meniscus tissues and explore biological sex-related differences.Methods: Tissue-engineered menisci were made from female and male meniscus fibrochondrocytes (MFCs) under static conditions of normal gravity in chondrogenic media and subjected to SMG and CHP culture. Constructs were assayed via histology, immunofluorescence, GAG/DNA assays, RNA sequencing, and testing of mechanical properties.Results: The mRNA expression of ACAN and COL2A1, was upregulated by CHP but downregulated by SMG. COL10A1, a marker for chondrocyte hypertrophy, was downregulated by CHP compared to SMG. Furthermore, CHP increased GAG/DNA levels and wet weight in both female and male donors, but only significantly in females. From the transcriptomics, CHP and SMG significantly modulated genes related to the ossification, regulation of ossification, extracellular matrix, and angiogenesis Gene Ontology (GO) terms. A clear difference in fold-change magnitude and direction was seen between the two treatments for many of the genes. Furthermore, differences in fold-change magnitudes were seen between male and female donors within each treatment. SMG and CHP also significantly modulated genes in OA-related KEGG pathways, such as mineral absorption, Wnt signalling pathway, and HIF-1 signalling pathway.Conclusion: Engineered menisci responded to CHP and SMG in a sex-dependent manner. SMG may induce an OA-like profile, while CHP promotes chondrogenesis. The combination of SMG and CHP could serve as a model to study the early molecular events of KOA and potential drug-targetable pathways.

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“…Sex differences have been frequently assessed in the arthroplasty literature largely because women are more likely to develop osteoarthritis due to combined metabolic, hormonal, and structural etiologies. 30 Despite the increased osteoarthritis rates prevalent in women, orthopaedic surgeons are less likely to refer female patients for total knee arthroplasty, 31 and physicians are more likely to attribute pain to psychological causes, 32 which together may lead to presentation at a later disease state.…”

Section: Discussionmentioning

confidence: 99%

Diversity in Orthopaedic Surgery Medical Device Clinical Trials: An Analysis of the Food and Drug Administration Safety and Innovation Act

Issa

Lambrechts

Lin

et al. 2022

J Am Acad Orthop Surg

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Introduction: Demographic factors contribute markedly to orthopaedic surgery outcomes. However, women and minorities have been historically excluded from clinical trials. The United States passed the Safety and Innovation Act (Food and Drug Administration Safety and Innovation Act [FDA-SIA]) in 2012 to increase study diversity and mandate reporting of certain demographics. The purpose of this study was to investigate demographic reporting and analysis among high-risk orthopaedic medical device trials and evaluate the effectiveness of the FDA-SIA in increasing diversity of study enrollment. Methods: The premarket approval database was queried for all original submissions approved by the Orthopedic Advisory Committee from January 1, 2003, to July 1, 2022. Study demographics were recorded. Weighted means of race, ethnicity, and sex were compared before and after FDA-SIA implementation with the US population. Results: We identified 51 orthopaedic trials with unique study data. Most Food and Drug Administration device trials reported age (98.0%) and sex (96.1%), but only 49.0% and 37.3% reported race and ethnicity, respectively. Only 23 studies analyzed sex, six analyzed race, and two analyzed ethnicity. Compared with the US population, participants were overwhelmingly White (91.36% vs. 61.63%, P , 0.001) with a significant underrepresentation of Black (3.65% vs. 12.41%, P = 0.008), Asian (0.86% vs. 4.8%, P = 0.030), and Hispanic participants (3.02% vs. 18.73%, P , 0.001) before 2013. The FDA-SIA increased female patient enrollment (58.99% vs. 47.96%, P = 0.021) but did not increase the enrollment of racial or ethnic minorities. Conclusion: Despite efforts to increase the generalizability of studies within the FDA-SIA, orthopaedic medical devices still fail to enroll

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Understanding the Observed Sex Discrepancy in the Prevalence of Osteoarthritis

Cited by 18 publications

References 103 publications

The Association Between Sex and Osteoarthritis in the Physically Active Population: A Systematic Review

The Association Between Sex and Osteoarthritis in the Physically Active Population: A Systematic Review

Engineered Human Meniscus in Modeling Sex Differences of Knee Osteoarthritis in Vitro

Diversity in Orthopaedic Surgery Medical Device Clinical Trials: An Analysis of the Food and Drug Administration Safety and Innovation Act

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