# Influence of major trauma and lower limb loss on radiographic progression and incidence of knee osteoarthritis and pain: a comparative and predictive analysis from the ADVANCE study

## TL;DR

This study finds that major trauma and lower limb loss increase the risk of knee osteoarthritis and pain, with different progression patterns over time.

## Contribution

The study provides new insights into how trauma and limb loss uniquely influence knee osteoarthritis and pain progression.

## Key findings

- Lower-limb loss is associated with increased radiographic OA incidence (IRR:1.98).
- Trauma-exposed individuals without limb loss show higher KP incidence (IRR:1.45).
- No predictive model explains a large proportion of variance in OA or pain progression.

## Abstract

Knee osteoarthritis (OA) is a leading cause of disability globally, with previous injury a key risk factor. This study investigates the relationship between the risk of progression and incidence of knee radiographic OA (rOA) and pain (KP) with major traumatic injury and identify potential predictors for rOA and KP.

The longitudinal ADVANCE cohort study observes UK male military personnel, n=579 sustained combat-injury and n=565 uninjured, frequency-matched for age, rank, role, service, and deployment, in Afghanistan (2003-2014). Participants had bilateral radiographs (unless amputated), pain questionnaires, six-minute walk-tests, and serum collected, 8- and 11-years post-injury (Baseline and Follow-up). We compared rates and risk of rOA and KP incidence and progression and assessed the performance of twenty potential demographic, joint-specific and molecular predictors.

Knee rOA and KP incidence and progression rates increased between Baseline and Follow-up. rOA progression did not differ between trauma-exposed and unexposed groups; however, KP progression increased for those sustaining a specific knee injury (IRR:2.53, 95% CI:1.08-5.92. Increased rOA incidence was seen in those with lower-limb loss (IRR:1.98, 95% CI:1.21-2.95), and KP incidence in trauma-exposed participants with no limb-loss or knee injury (IRR:1.45, 95% CI:1.05-2.01). No predictive model explained a large proportion of variance for rOA or KP incidence or progression.

Our results are consistent with a short post-injury window of increased rOA incidence, followed by a plateau. Comparatively, individuals with lower-limb loss experience a similar increase due to trauma, and then continue a steeper decline in joint-health due to altered joint biomechanics and mechanoinflammation.

The online version contains supplementary material available at 10.1186/s13075-026-03739-4.