Hardy · Journal of cachexia, sarcopenia and muscle 2022 · systematic review and meta-analysis · n=29 studies (695 participants)

The time course of disuse muscle atrophy of the lower limb in health and disease.

Cited 80 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of prospective disuse and immobilization studies

PubMed 36104842 · doi:10.1002/jcsm.13067 · record verified 2026-08-30

What was done

A systematic review and random-effects meta-analysis (MEDLINE, Embase, CINAHL, and CENTRAL from inception to April 2021) evaluated the time course of disuse muscle atrophy (DMA) in immobilized human lower limbs across healthy volunteers, intensive therapy unit (ITU) patients, and ankle fracture patients. Studies measuring muscle volume, cross-sectional area, architecture, or lean leg mass across multiple post-immobilization timepoints were included, and risk of bias was assessed using ROBINS-I.

What was found

Twenty-nine studies were included (12 in healthy volunteers, n = 140; 18 in ITU patients, n = 516; 3 in ankle fracture patients, n = 39). Quadriceps atrophy rate over the first 14 days was significantly greater in ITU patients (mean difference -1.01, 95% CI -1.32 to -0.69) than in healthy cohorts (mean difference -0.12, 95% CI -0.49 to 0.24) (P < 0.001). Atrophy rates at day 28 varied by muscle group: triceps surae (-11.2%), quadriceps (-9.2%), hamstrings (-6.5%), and foot dorsiflexors (-3.2%). Atrophy rates decreased over time in healthy quadriceps (-6.5% at day 14 vs. -9.1% at day 28), healthy triceps surae (-7.8% at day 14 vs. -11.2% at day 28), and ITU quadriceps (-13.2% at day 7 vs. -28.2% at day 14).

Why it matters

This review shows that disuse muscle loss is non-linear—accelerating primarily in the initial days of immobilization—and is markedly exacerbated by critical illness, identifying antigravity muscles (triceps surae and quadriceps) as primary targets for early physical rehabilitation.

Limits

The majority of included studies had a moderate risk of bias. Healthy and fracture cohorts had small sample sizes, and wide heterogeneity in muscle measurement techniques limited meta-analysis across all outcomes and timepoints.

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