Chronic Pain and Residual Limb Outcomes Following Primary Major Lower Extremity Amputation vs. Minor-to-Major Amputation Progression: A Propensity Score-Matched Analysis

Introduction: It is unclear if the pathway to major lower-extremity amputation (LEA) impacts development of post-amputation pain. This study compares pain outcomes between patients with minor LEA progressing to major amputation versus primary major LEA. Methods: Adults with major LEA (proximal to the ankle) were identified from the TriNetX Global Collaborative Network (2010–2026). Patients with an initial minor LEA (distal to the ankle) followed by a subsequent, distinct major LEA were compared with patients undergoing primary major LEA via propensity score matching across a total of 99 covariates. Patients with progression were further stratified using six intervals (0–3, 3–6, and 6–12 months, and ≥1, ≥2, and ≥5 years) corresponding to time between amputations. Outcomes were assessed using two-proportion z-tests and Kaplan–Meier time-to-event analysis. Results: Matched cohorts ranged from 997 to 6245 patients per group across the six intervals. Overall, patients with progressive minor-to-major LEA had highly significant, higher rates of residual limb pain (RLP) (risk difference range: 4.3–8.5%), phantom limb pain (PLP) (2.6–4.9%), and amputation revision or complications (10.9–17.2%) that persisted for five years after major amputation. Progression at 3–12 months displayed the highest risk differences for RLP (7.8–8.5%), progression within one year, the highest for revisions, while PLP displays an increased risk not dependent on progression interval. Progression was also associated with lower mortality if progression occurred more than 1 year from the minor amputation. Conclusions: Minor-to-major progression of LEA is associated with significantly worse chronic pain and amputation revisions in highly co-morbid patients. Progression represents a high-risk, and potentially high yield, population to target for earlier interventions to improve pain. RLP may be modifiable after the minor LEA to optimize outcomes after the major LEA while PLP appears to be driven primarily by the major LEA.