Mirko Mandić

This research proposal is submitted in response to the Swedish National Space Agency (SNSA) call 2024-R for research funding. The project presented here has been selected for definition by the European Space Agency (ESA) on March 5, 2024 as part of the “Announcement of Opportunity soliciting for experiments to perform retrospective analysis on the anonymised data of seven bedrest studies (AO-2023-BedrestCoreData)”.The response of the musculoskeletal system to microgravity has been extensively studied, and there are many studies reporting on the effects of bed rest on bone or skeletal muscle. However, despite sporadic attempts to explore the interactions between the different tissues of the musculoskeletal system, knowledge of the interactions between these tissues is surprisingly limited. Furthermore, the individual response to the changes induced by bed rest is not yet clearly defined.We propose a study that takes a holistic and integrative approach to understand the musculoskeletal changes induced by bed rest and the possible individual responses. Specifically, this project aims to:Investigate the interaction between bed rest-induced skeletal muscle and bone changes.Define the time course of bone and muscle changes during bed rest.Explore the individual responses to bed rest-induced muscle and bone changes.In addition, we plan to examine the effects of various countermeasures on musculoskeletal adaptations to bed rest, develop prediction models for bed rest-induced muscle and bone changes, investigate early muscle and bone recovery and possible relationships between these two tissues, and finally determine whether cardiovascular changes, sleep quality, and psychological status influence muscle and bone changes and interactions in response to bed rest.To accomplish the goals of the project, we will use data from 7 ESA-funded bed rest studies comprising ~170 individual observations on bed rest only or bed rest plus a specific countermeasure. Data include bone biomarkers in blood and urine, dual-energy X-ray absorptiometry variables, regular and high-resolution peripheral quantitative computed tomography, muscle function (vertical jump capacity, maximal strength, and muscle fatigue), aerobic capacity, plasma volume, orthostatic tolerance, computerized dynamic posturography, body mass, health, mood and sleep questionnaires, and vital signs. The data will be curated and advanced statistical analysis methods will be used to achieve the goals of the project.To ensure the success of this ambitious project, we have assembled a highly qualified team of specialists with extensive experience in space and musculoskeletal physiology research. The researchers involved in this application have extensive experience in spaceflight and bed rest experiments and have worked with multiple data sets related to the current application (muscle and bone imaging, blood and urine biomarkers, performance outcomes, etc.). The added value created by this international collaboration will therefore allow us to achieve the objectives of this comprehensive project.The current project will deliver important and novel knowledge to better understand the musculoskeletal changes induced by bed rest and the interactions between the different tissues of this system. This information has the potential to help fine-tune selection procedures for crewed space missions and personalize countermeasures during space exploration missions. In addition, this work will increase the understanding of musculoskeletal changes suffered by clinical populations experiencing severe inactivity.