Pre-flight exercise and bone metabolism predict unloading-induced bone loss due to spaceflight

Abstract

ObjectivesBone loss remains a primary health concern for astronauts, despite in-flight exercise. We examined changes in bone microarchitecture, density and strength before and after long-duration spaceflight in relation to biochemical markers of bone turnover and exercise.MethodsSeventeen astronauts had their distal tibiae and radii imaged before and after space missions to the International Space Station using high-resolution peripheral quantitative CT. We estimated bone strength using finite element analysis and acquired blood and urine biochemical markers of bone turnover before, during and after spaceflight. Pre-flight exercise history and in-flight exercise logs were obtained. Mixed effects models examined changes in bone and biochemical variables and their relationship with mission duration and exercise.ResultsAt the distal tibia, median cumulative losses after spaceflight were −2.9% to −4.3% for bone strength and total volumetric bone mineral density (vBMD) and −0.8% to −2.6% for trabecular vBMD, bone volume fraction, thickness and cortical vBMD. Mission duration (range 3.5–7 months) significantly predicted bone loss and crewmembers with higher concentrations of biomarkers of bone turnover before spaceflight experienced greater losses in tibia bone strength and density. Lower body resistance training volume (repetitions per week) increased 3–6 times in-flight compared with pre-spaceflight. Increases in training volume predicted preservation of tibia bone strength and trabecular vBMD and thickness.ConclusionsFindings highlight the fundamental relationship between mission duration and bone loss. Pre-flight markers of bone turnover and exercise history may identify crewmembers at greatest risk of bone loss due to unloading and may focus preventative measures.

Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice

“…This process produces distinct molecular signals that can be detected in serum. Our results demonstrated slightly increased (though not significant) serum levels of bone resorption marker CTx, which was also reported in astronauts as early as 15 days in space by Gabel et al [ 84 ]. Furthermore, in agreement with previous findings of other groups [ 12 , 43 , 86 ] the expressions of late/terminal osteoclast differentiation markers, Acp5 and Ctsk were significantly increased in bone shafts of our GCR exposed mice.…”

“…Lang et al (2004) reported a significant endocortical thinning in crewmembers after 4–6-month flights on the International Space Station, although similar to our results, they also found no significant compartment-specific bone loss in the spine. Interestingly, a very recent study exhibited significant decreases in trabecular bone volume fraction and thickness, with no changes in cortical porosity or thickness in the tibias of 17 astronauts following a >3-month mission [ 84 ]. However, they also reported a significant decrease in cortical volumetric bone density.…”

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

“…For example, astronauts lose bone mineral density, trabecular volume, and strength upon spaceflight for 6 months together with increased serum bone turnover makers. Resistive exercise attenuates spaceflight-induced loss in bone mass and trabecular thickness [ 60 ]. A similar study conducted by Sibonga et al also show that long-term spaceflight accelerates bone loss in astronauts [ 61 ].…”

Global transcriptomic analysis of a murine osteocytic cell line subjected to spaceflight

“…3,4 Long-duration spaceflight missions are associated with an increased risk of bone fractures and kidney stones. [5][6][7][8][9] Unraveling the detailed molecular mechanisms underlying microgravity (µG) and disuse-induced bone loss is critical for developing new therapeutic countermeasures both for future long-duration spaceflight missions and for enhancing the care of immobilized patients often encountered in the healthcare setting. Growing evidence suggests that osteocytes, the most abundant skeletal cells, out-numbering both osteoblasts and osteoclasts in adult bone, and deeply embedded within the mineralized matrix of bone, play a key role in sensing mechanical forces applied to the skeleton and in transducing changes into subcellular biochemical signals required to maintain bone homeostasis.…”

“…Conversely, during long‐term spaceflight, prolonged bed rest, or immobilization after spinal cord injury, mechanical forces are reduced and it is hypothesized this reduction in loading is directly responsible for the losses in bone mineral density and strength along with an increase in urinary calcium levels 3,4 . Long‐duration spaceflight missions are associated with an increased risk of bone fractures and kidney stones 5‐9 . Unraveling the detailed molecular mechanisms underlying microgravity (µG) and disuse‐induced bone loss is critical for developing new therapeutic countermeasures both for future long‐duration spaceflight missions and for enhancing the care of immobilized patients often encountered in the healthcare setting.…”