BACKGROUND: Bone mineral density (BMD) is a measure of skeletal health that may foretell disorders like osteoporosis.METHODS: To reduce bone losses on Earth, treatments include exercise, diet, and drugs. Each impact osteoblast and osteoclast activity dictates skeletal remodeling and subsequent BMD changes. BMD loss is a concern during spaceflight. For astronauts, low BMD undermines in-flight tasks and compromises their postflight health.RESULTS: While bisphosphonates exhibited promise as an in-flight bone loss treatment, study results are mixed, and this class of drugs has numerous side-effects. While the role antiresorptive agents play in reducing BMD loss is discussed, this review focuses on exercise-induced strains and nutrition, two in-flight treatments without bisphosphonates' side-effects.DISCUSSION: Evidence supports in-flight exercise and a healthy diet with vitamin D and Ca+2 supplementation to limit BMD loss. This review suggests how exercise and nutrition may limit BMD loss during spaceflight. Also discussed is an in-flight version of the inertial exercise trainer (IET; Impulse Technologies, Knoxville TN). By imparting high bone-strain magnitudes, rates, and frequencies with less mass, footprint, and power needs than other forms of in-flight resistance exercise hardware, the IET warrants inquiry for use aboard future long-term spaceflights.Caruso J, Patel N, Wellwood J, Bollinger L. Impact of exercise-induced strains and nutrition on bone mineral density in spaceflight and on the ground. Aerosp Med Hum Perform. 2023; 94(12):923-933.