Multilevel meta-analysis of therapeutic interventions to improve fall-related outcomes in individuals with lower limb amputation

Objective: To evaluate the effectiveness of therapeutic interventions on gait, balance, functional independence, and balance confidence in individuals with lower limb amputation. In addition, to examine effects by intervention type and determine their clinical significance. Data Sources: Seven databases (AMED, APA PsycInfo, Medline, CINAHL, PubMed, Scopus, Web of Science) were searched up to May 26, 2025. Reference lists of included studies and related systematic reviews were also screened. Study Selection: Studies were included if they evaluated a therapeutic intervention in adults with lower limb amputation, had evidence of reliability, validity, and responsiveness in people with limb amputation, and had a Physiotherapy Evidence Database score ≥6. Twenty-one studies met inclusion criteria; 18 were included in the meta-analysis. Data Extraction: Studies were divided across 6 reviewers, who then independently extracted data using a standardized form (participant characteristics, intervention type and duration, outcome measures, and results). Study quality was reported using the Physiotherapy Evidence Database scale. Data Synthesis: Twenty-one studies (654 participants) contributed 34 gait outcomes (13 studies), 26 balance outcomes (10 studies), 11 functional independence outcomes (8 studies), and 5 balance confidence outcomes (5 studies). A 3-level random-effects meta-analysis showed that therapeutic interventions statistically significantly improved gait (standardized mean difference [SMD] =0.54), balance (SMD=0.68), and functional independence (SMD=0.30), with smaller effects on balance confidence (SMD=0.27). Cognitive training had the largest effect on gait, exercise on balance, virtual reality on balance confidence, and proprioceptive neuromuscular facilitation on functional independence. All effects were statistically significant except virtual reality on balance confidence. Only 7 of 54 outcomes met minimal clinically important difference or minimal detectable change thresholds. Conclusions: Therapeutic interventions improve functional outcomes in individuals with a lower limb amputation, although clinical significance was limited. Future research should tailor interventions and standardize outcome measures to better align with meaningful patient improvements.