The purpose of this systematic review is twofold: 1) to identify, evaluate, and synthesize the heretofore disparate scientific literatures regarding the effects of direct exposure to microgravity on the musculoskeletal system, taking into account for the first time both bone and muscle systems of both humans and animals; and 2) to investigate the efficacy and limitations of exercise countermeasures on the musculoskeletal system under microgravity in humans.The Framework for Scoping Studies (Arksey and O'Malley 2005) and the Cochrane Handbook for Systematic Reviews of Interventions (Higgins JPT 2011) were used to guide this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was utilized in obtaining the combined results (Moher, Liberati et al. 2009). Data sources, PubMed, Embase, Scopus, and Web of Science were searched for published articles through October 2019 using the Mesh terms of microgravity, musculoskeletal system, and exercise countermeasures. A total of 84 references were selected, including 40 animal studies and 44 studies with human participants. The heterogeneity in the study designs, methodologies, and outcomes deemed this review unsuitable for a meta-analysis. Thus, we present a narrative synthesis of the results for the key domains under five categories: 1) Skeletal muscle responses to microgravity in humans 2) Skeletal muscle responses to microgravity in animals 3) Adaptation of the skeletal system to microgravity in humans 4) Adaptation of the skeletal system to microgravity in animals 5) Effectiveness of exercise countermeasures on the human musculoskeletal system in microgravity. Existing studies have produced only limited data on the combined effects on bone and muscle of human spaceflight, despite the likelihood that the effects on these two systems are complicated due to the components of the musculoskeletal system being anatomically and functionally interconnected. Bone is directly affected by muscle atrophy as well as by changes in muscle strength, notably at muscle attachments. Given this interplay, the most effective exercise countermeasure is likely to be robust, individualized, resistive exercise, primarily targeting muscle mass and strength.

• MeSH
• Time Factors MeSH
• Risk Assessment MeSH
• Space Flight * MeSH
• Humans MeSH
• Musculoskeletal Diseases diagnosis   etiology   physiopathology   prevention & control   MeSH
• Musculoskeletal System pathology   physiopathology   MeSH
• Protective Factors MeSH
• Weightlessness Countermeasures * MeSH
• Risk Factors MeSH
• Weightlessness adverse effects   MeSH
• Exercise Therapy * MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Scoping Review MeSH