Strategies for studying bone loss in microgravity

Astronauts are prone to a condition known as disuse osteoporosis as the microgravity environment negates the need for skeletal weight bearing. Recently, the development of new strategies to study bone loss in microgravity has been advancing at a rapid pace. As a result, several emerging technologies have paved the way for new research into the cellular and physiological mechanisms involved in disuse osteoporosis. In this review, we discuss the most impactful and current methodologies and technologies for both in vivo and in vitro studies of bone loss in space and with simulators on Earth from the past decade. We cover research performed on the International Space Station, uncrewed satellites, head-down tilt bed rest, rodent hindlimb unloading, and 2D/3D clinorotation for cell culture which are all established methods to mechanically unload the skeleton and/or bone cells. We also summarize the experimental findings documenting the changes that occur following exposure to unloading on a macroscopic scale, such as morphometric changes to the bone structure, and on the microscopic scale, such as effects on bone-forming osteoblasts, bone-resorbing osteoclasts, and mechanical stress-sensing osteocytes.