Author Identifier (ORCID)
Robert U. Newton: https://orcid.org/0000-0003-0302-6129
Nicolas H. Hart: https://orcid.org/0000-0003-2794-0193
Abstract
Background: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. Methods: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). Results: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I2 = 76%). This effect remained significant in multilevel analyses accounting for within-study dependence (ES = 0.58, 95% CI [0.19, 0.96]; p = 0.003). During bed rest, conventional random-effects analyses indicated large effects (ES = 1.16, 95% CI [0.60, 1.71]; p < 0.0001; I2 = 55%); however, multilevel models incorporating correlated lower limb strength and power outcomes showed no significant pooled effect (ES = 0.06, 95% CI [−1.31, 1.43]; p = 0.93). In contrast, spaceflight studies demonstrated small, nonsignificant effects on muscle strength and power (ES = 0.10, 95% CI [−0.32, 0.51]; p = 0.65), and pooled standardized mean change analyses indicated no significant overall change in muscle mass (ES = 0.002, 95% CI [−0.077, 0.080]; p = 0.966). When exercise was applied therapeutically after disuse, a trend toward improved muscle strength and power was observed (ES = 0.23, 95% CI [−0.01, 0.47]; p = 0.06; I2 = 12%), although multilevel models showed no significant effects (ES = 0.30, 95% CI [−0.34, 0.95]; p = 0.361). Exercise significantly preserved or increased muscle mass during bed rest (ES = 0.47, 95% CI [0.19, 0.74]; p = 0.0009) and spaceflight (ES = 0.27, 95% CI [0.05, 0.48]; p = 0.02). Conclusion: Exercise, particularly resistance training, attenuates muscle strength loss and preserves muscle mass during hospitalization and bed rest, whereas no consistent benefits are observed during spaceflight. Exercise initiated after disuse shows modest potential for restoring muscle function. Current evidence is insufficient to determine whether preventive or therapeutic initiation provides superior outcomes. Further high-quality randomized controlled trials are required to define the optimal timing, modality and dose of exercise for clinical rehabilitation and aerospace applications.
Keywords
Atrophy, functional capacity, immobility, resistive exercise, unloaded muscle
Document Type
Journal Article
Date of Publication
4-1-2026
Volume
17
Issue
2
PubMed ID
41983453
Publication Title
Journal of Cachexia, Sarcopenia and Muscle
Publisher
Wiley
School
Exercise Medicine Research Institute / School of Medical and Health Sciences
Funders
This study was supported by São Paulo Research Foundation (FAPESP) and Coordenação de Aperfeiçoamento Pessoal de Nível Superior— Brazil (CAPES) #001. CSP has been granted Post Doctorate fellowship from FAPESP (Process 2018/23402- 0), CF has been granted Doctorate scholarship from FAPESP (Process 2019/26378- 6), and FSL has been granted research grants from FAPESP (Process 2018/19678- 0) and scholarship (PQ B) from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Process 303650/2024- 9). FSL and JCRN have been granted research grants from the CCD/CMEPP FAPESP (Process 2025/07056- 9). RUN is a Vice Chancellor Professorial Fellow. NHH is a National Health and Medical Research Council Investigator Fellow (APP2017080).
Grant Number
NHMRC Number : APP2017080
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Padilha, C. S., Figueiredo, C., Deminice, R., Ribeiro, A. S., Newton, R. U., Hart, N. H., Rosa‐Neto, J. C., Seelaender, M., & Lira, F. S. (2026). Disuse-induced muscle atrophy and muscle weakness from hospitalization to spaceflight: Exercise succeeds in prevention and treatment—A meta-analysis. Journal of Cachexia, Sarcopenia and Muscle, 17(2), e70259. https://doi.org/10.1002/jcsm.70259