If interplanetary travel is to be successful over the coming decades, it is essential that countermeasures to minimize deterioration of the musculoskeletal system are as effective as possible, given the increased duration of spaceflight associated with such missions. The aim of this review, therefore, is to determine the magnitude of deconditioning of the musculoskeletal system during prolonged spaceflight and recommend possible methods to enhance the existing countermeasures.

Methods
A literature search was conducted using PubMed, Ovid and Scopus databases. 5541 studies were identified prior to the removal of duplicates and the application of the following inclusion criteria: (1) group means and standard deviations for pre- and post-spaceflight for measures of strength, muscle mass or bone density were reported (or provided by the corresponding author when requested via e-mail), (2) exercise-based countermeasures were included, (3) the population of the studies were human, (4) muscle function was assessed and (5) spaceflight rather than simulated spaceflight was used. The methodological quality of the included studies was evaluated using a modified Physiotherapy Evidence Database (PEDro) scale for quality, with publication bias assessed using a failsafe N (Rosenthal method), and consistency of studies analysed using I2 as a test of heterogeneity. Secondary analysis of studies included Hedges’ g effect sizes, and between-study differences were estimated using a random-effects model.

Results
A total of 11 studies were included in the meta-analyses. Heterogeneity of the completed meta-analyses was conducted revealing homogeneity for bone mineral density (BMD) and spinal muscle size (Tau2 < 0.001; I2 = 0.00%, p > 0.05), although a high level of heterogeneity was noted for lower body force production (Tau2 = 1.546; I2 = 76.03%, p < 0.001) and lower body muscle mass (Tau2 = 1.386; I2 = 74.38%, p < 0.001). The estimated variance (≤ -0.306) for each of the meta-analyses was significant (p ≤ 0.033), for BMD (− 0.48 to − 0.53, p < 0.001), lower body force production (− 1.75, p < 0.001) and lower body muscle size (− 1.98, p < 0.001). Spaceflight results in small reductions in BMD of the femur (Hedges g = − 0.49 [− 0.69 to – 0.28]), trochanter (Hedges g = − 0.53 [− 0.77 to – 0.29]), and lumbo-pelvic region (Hedges g = − 0.48 [− 0.73 to – 0.23]), but large decreases in lower limb force production (Hedges g = − 1.75 [− 2.50 to – 0.99]) and lower limb muscle size (Hedges g = − 1.98 [− 2.72 to – 1.23]).

Conclusions
Current exercise countermeasures result in small reductions in BMD during long-duration spaceflight. In contrast, such exercise protocols do not alleviate the reductions in muscle function or muscle size, which may be attributable to the low to moderate loads reported by crewmembers and the interference effect associated with concurrent training. It is recommended that higher-load resistance exercise and the use of high-intensity interval training should be investigated, to determine if such modifications to the reported training practices result in more effective countermeasures to the deleterious effect of long-duration spaceflight on the muscular system.