**Background:** Periods of skeletal muscle disuse from illness, injury, or surgery cause rapid declines in muscle strength and size, increasing risks of metabolic disease and functional impairment. Single-leg disuse models (casting, bracing, suspension) are commonly used to study these effects, but prior meta-analyses were limited. This study aimed to systematically quantify changes in muscle strength, size, and power following single-leg disuse in uninjured adults, and to compare effects by disuse duration and model type (cast vs. brace).
**Methods:** The review followed PRISMA guidelines and was pre-registered (OSF). Searches were conducted in EMBASE, Medline, CCRCT, and CINAHL (initial: Dec 14, 2020; update: Jan 20, 2022). Inclusion criteria: original experimental studies in uninjured humans using unilateral leg immobilization and reporting muscle size, strength, or power. Two independent reviewers screened and extracted data. Risk of bias was assessed using the Cochrane Collaboration tool; quality of evidence via GRADE. Meta-analyses used random-effects models with Hedges' gav effect sizes. Subgroup analyses examined disuse duration (≤7, >7–≤14, >14 days) and model (cast vs. brace at 14 days).
**Key Results:** Of 6548 screened records, 86 studies were included in the systematic review and 40 in meta-analyses (35 for strength, 20 for size; 15 reported both). Most studies (88%) were published since 2000; 36% included females; 13% included adults >40 years. Only one study presented sex-disaggregated data. The overall weighted effect size for leg extensor strength across all durations was −0.80 (95% CI: −0.92 to −0.68; P < 0.001; N = 35 studies, n = 429 participants). For leg extensor size, the overall effect was −0.41 (95% CI: −0.51 to −0.31; P < 0.001; N = 20 studies, n = 233). Subgroup analyses showed strength declines increased with duration: ≤7 days (−0.57 [−0.75, −0.40]; N = 9), >7–≤14 days (−0.93 [−1.12, −0.74]; N = 17), >14 days (−0.95 [−1.20, −0.70]; N = 9). Size declines similarly increased: ≤7 days (−0.26 [−0.36, −0.16]; N = 7), >7–≤14 days (−0.49 [−0.67, −0.30]; N = 8), >14 days (−0.52 [−0.74, −0.30]; N = 6). At 14 days, strength loss was −23 ± 6% (range −36 to −10%; N = 24 studies) and quadriceps size loss was −8 ± 3% (range −15 to −5%; N = 12). No significant difference was found between cast and brace models for strength (cast: −0.94 [−1.30, −0.59], N = 7; brace: −0.90 [−1.18, −0.63], N = 7; P = 0.86) or size (cast: −0.61 [−0.87, −0.35], N = 3; brace: −0.48 [−1.04, 0.07], N = 3; P = 0.68) at 14 days. I² was 0% for all meta-analyses except strength across all durations (10.1% after trim-and-fill). Egger's test suggested possible publication bias for strength (P = 0.03) but not size (P = 0.16). A meta-analysis for muscle power was not performed due to insufficient comparable data points.
**Clinical Implications:** This study provides robust, quantitative evidence that single-leg disuse causes significant and rapid declines in muscle strength and size, with strength losses outpacing size losses—a finding relevant to rehabilitation and sarcopenia prevention. The plateauing of losses after 14 days suggests early intervention is critical. The interchangeability of cast and brace models offers practical flexibility for researchers. However, the severe underrepresentation of females, older adults (>40 years), and middle-aged populations limits generalizability. Only 36% of studies included females and 13% included adults >40 years. The authors call for future studies to include sex-disaggregated data and older participants. The effect sizes reported can inform a priori power calculations for future disuse research.