This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bedrest is an excellent analog for the study of on-orbit musculoskeletal changes that occur during long-duration spaceflight. Our novel approach involves quantifying typical daily loads to the lower extremities in selected free-living volunteer subjects who are not habitual exercisers and planning individual exercise prescriptions based on daily load stimulus theory. Subjects will then be randomized to control or exercise groups and confined to 6-degree head-down bedrest in the General Clinical Research Center (GCRC) at the Cleveland Clinic Foundation (CCF) for 12 weeks. During this time, the exercise group will undergo individualized daily exercise programs in the unique Zero Gravity Locomotion Simulator (ZLS) at CCF designed to replace their daily mechanical load stimulus experienced during free living. A treadmill and a resistance-exercise device similar to those available on the International Space Station will be used for exercise. DXA, MRI, and QCT scans will be conducted at the start and end of bedrest to assess variations in bone mineral density, changes in muscle volume, and regional changes (cortical vs. trabecular) in bone. DXA scans will also be conducted at week 8 of bedrest. Strength measurements will be collected pre- and post-bedrest, and urinary and serum markers of bone resorption and formation will also be assessed. Dietary intake sufficient to maintain constant body weight with a balanced intake of macro- and micronutrients will be planned and supervised by a registered dietician, and a GCRC physician will be available 24 hr/day to attend to any medical needs. A rehabilitation program will be offered to subjects in the 8 weeks following bedrest. The proposed experiment should provide a categorical answer to the question of whether intermittent load replacement can adequately protect the musculoskeletal system against hypokinetic osteopenia and muscle atrophy and may open a new era in individualized exercise countermeasure planning.
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