Sex Matters: Investigating the Influence of Presurgery Factors on Pain and Physical Function following Total Joint Arthroplasty for Osteoarthritis

Anthony V Perruccio; J Denise Power; Kala Sundararajan; Mayilee Canizares; J Roderick Davey; Rajiv Gandhi; Khalid Syed; Christian Veillette; Mohit Kapoor; Nizar N Mahomed; Y Raja Rampersaud

doi:10.2106/JBJS.OA.25.00232

Sex Matters: Investigating the Influence of Presurgery Factors on Pain and Physical Function following Total Joint Arthroplasty for Osteoarthritis

JB JS Open Access. 2025 Nov 3;10(4):e25.00232. doi: 10.2106/JBJS.OA.25.00232. eCollection 2025 Oct-Dec.

Authors

Anthony V Perruccio^{1

2

3

4}, J Denise Power^{1

2}, Kala Sundararajan¹, Mayilee Canizares^{1

2}, J Roderick Davey^{1

4}, Rajiv Gandhi^{1

3}, Khalid Syed^{1

4}, Christian Veillette^{1

4}, Mohit Kapoor^{1

4

5}, Nizar N Mahomed^{1

4}, Y Raja Rampersaud^{1

4}

Affiliations

¹ Schroeder Arthritis Institute, University Health Network, Toronto, Canada.
² Arthritis Community Research and Epidemiology Unit (ACREU), Toronto, Canada.
³ Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
⁴ Department of Surgery, University of Toronto, Toronto, Canada.
⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.

Abstract

Background: Despite broad calls to consider sex-specific effects in treatment/intervention studies, this remains a persistent gap. This study sought to identify presurgery factors associated with pain and physical function following hip and knee total joint arthroplasty (TJA) for osteoarthritis, specifically adopting a sex-stratified approach.

Methods: Questionnaires were patient-completed presurgery: sociodemographic and health-related characteristics, anxiety and depression symptoms, neuropathic-like pain symptoms, multijoint involvement, and opioid use. Pain and physical function were captured presurgery and 1 year postsurgery. Study outcomes: pain and function status scores at 1 year and their percentage change (presurgery to 1 year postsurgery). Associations between presurgery factors and outcomes were assessed by sex-stratified multivariable linear regressions. Findings were contrasted against a sex-adjusted approach (i.e. one analysis in combined male/female sample).

Results: Sample (45% hip, 55% knee): 787 female patients and 640 male patients. Among male patients only: Depressive symptoms were associated with worse pain and function status, and less pain improvement (β = -8.6% [-17.4%, 0.3%]), as were lower education and living alone. Among female patients only: Anxiety symptoms were associated with worse pain and function status and less pain (β = -7.7% [-14.3%, -1.0%) and functional improvement (β = -8.5% [-14.4%, -2.6%]), as was greater multijoint burden. The negative effect of neuropathic-like pain symptoms was greater in male patients than female patients. Sex-adjusted findings suggested sex had no consequence.

Conclusions: Several factors uniquely influenced TJA outcomes by sex. Simple sex-adjustment may miss important effects. This has broad implications, including for patient education, decision making, prognostic/comparative effectiveness study design, and development/improvement of prediction algorithms. Though TJA focused, we hypothesize that sex differences are likely relevant in other clinical populations.

Level of evidence: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.