Resistive exercise in astronauts on prolonged spaceflights provides partial protection against spaceflight-induced bone loss

Sibonga, Jean D.; Matsumoto, Toshio; Jones, Jeff; Shapiro, Jay R.; Lang, Thomas; Shackelford, Linda; Smith, Scott M.; Young, Millennia; Keyak, Joyce H.; Kohri, Kenjiro; Ohshima, Hiroshi; Spector, Elisabeth R.; LeBlanc, Adrian

doi:10.1016/j.bone.2019.07.013

Cited by 89 publications

(77 citation statements)

References 25 publications

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“…We show that targeting this signaling pathway has significant beneficial effects in protecting against both muscle and bone loss in microgravity, suggesting that this strategy may be effective in preventing or treating muscle and bone loss not only in astronauts on prolonged missions but also in people with disuse atrophy on Earth, such as in older adults or in individuals who are bedridden or wheelchair-bound from illness. like the International Space Station (ISS) (23,24), future exploration missions to destinations like Mars will be significantly longer (∼3 y) and impose mass constraints that will not allow for the same, highly effective exercise equipment. Thus, therapeutic strategies, such as those related to MSTN/activin A signaling, may be critical to maintain astronaut health in such missions.…”

Section: Significancementioning

confidence: 99%

Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight

Lee

Lehar

Meir

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Among the physiological consequences of extended spaceflight are loss of skeletal muscle and bone mass. One signaling pathway that plays an important role in maintaining muscle and bone homeostasis is that regulated by the secreted signaling proteins, myostatin (MSTN) and activin A. Here, we used both genetic and pharmacological approaches to investigate the effect of targeting MSTN/activin A signaling in mice that were sent to the International Space Station. Wild type mice lost significant muscle and bone mass during the 33 d spent in microgravity. Muscle weights of Mstn−/− mice, which are about twice those of wild type mice, were largely maintained during spaceflight. Systemic inhibition of MSTN/activin A signaling using a soluble form of the activin type IIB receptor (ACVR2B), which can bind each of these ligands, led to dramatic increases in both muscle and bone mass, with effects being comparable in ground and flight mice. Exposure to microgravity and treatment with the soluble receptor each led to alterations in numerous signaling pathways, which were reflected in changes in levels of key signaling components in the blood as well as their RNA expression levels in muscle and bone. These findings have implications for therapeutic strategies to combat the concomitant muscle and bone loss occurring in people afflicted with disuse atrophy on Earth as well as in astronauts in space, especially during prolonged missions.

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Section: Significancementioning

confidence: 99%

Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight

Lee

Lehar

Meir

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…There have also been variable reports of resistance exercise to be a countermeasure to disuse‐induced bone loss . Leblanc and colleagues utilized a newer advanced resistance‐exercise device with bisphosphonates to demonstrate the protection of bone during spaceflight with increases from BMD scans, elevated measures of bone‐resorption markers, and urinary excretion of calcium . Shackelford and colleagues used a specially designed and NASA‐developed horizontal exercise machine as a method of resistance exercise for patients undergoing 17 weeks of horizontal bed rest .…”

Section: Introductionmentioning

confidence: 99%

“…(13,(15)(16)(17)(18)(19) Leblanc and colleagues utilized a newer advanced resistance-exercise device with bisphosphonates to demonstrate the protection of bone during spaceflight with increases from BMD scans, elevated measures of bone-resorption markers, and urinary excretion of calcium. (9,20) Shackelford and colleagues used a specially designed and NASA-developed horizontal exercise machine as a method of resistance exercise for patients undergoing 17 weeks of horizontal bed rest. (13) Patients using the resistance-training protocol had significantly different lumbar, hip, calcaneus, and pelvis BMDs, indicating that the exercise regime had a positive treatment affect for patients in situations such as prolonged bed rest and spaceflight.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Controlled Mechanical Loading of Bone in C57BL6/J Mice Subject to Disuse

et al. 2019

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Prolonged reduction in weightbearing causes bone loss. Disuse of bone is associated with recovery from common musculoskeletal injury and trauma, bed rest resulting from various medical conditions, and spaceflight. The hindlimb‐suspension rodent model is popular for simulating unloading and disuse. We hypothesized that controlled mechanical loading of the tibia would protect against bone loss occurring from concurrent disuse. Additionally, we hypothesized that areas of high mechanical peak strains (midshaft) would provide more protection than areas of lower strain (distal shaft). Adult C57BL6/J mice were suspended for 3 weeks, with one limb subjected to tibial compression four times per week. μCT imaging was completed at days 0, 11, and 21, in addition to serum analysis. Significant bone loss caused by hindlimb suspension was detected in trabecular bone by day 11 and worsened by day 21 (p < 0.05). Bone loss was also detected in cortical thickness and area fraction by day 21. However, four short bouts per week of compressive loading protected the loaded limb from much of this bone loss. At day 21, we observed a 50% loss in trabecular bone volume/total volume and a 6% loss in midshaft cortical thickness in unloaded limbs, but only 15% and 2% corresponding losses in contralateral loaded limbs (p = 0.001 and p = 0.02). Many bone geometry parameters of the loaded limbs of suspended animals did not significantly differ from non‐suspended control limbs. Conversely, this protective effect of loading was not detected in cortical bone at the lower‐strained distal shaft. Analysis of bone metabolism markers suggested that the benefits of loading occurred through increased formation instead of decreased resorption. This study uniquely isolates the role of externally applied mechanical loading of the mouse tibia, in the absence of muscle stimulation, in protecting bone from concurrent disuse‐related loss, and demonstrates that limited bouts of loading may be highly effective during prolonged disuse. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…Countermeasures to preserve muscular strength and endurance and BMD in astronauts include aerobic and resistive exercise together with nutritional supplementation, high dose vitamin D, and bisphosphonates ( LeBlanc et al, 2013 ; Scheuring, 2016 ; Swaffield et al, 2018 ). A study of astronauts aboard the ISS, has shown that the bisphosphonate therapy together with resistive exercise is more effective in preserving BMD than exercise alone ( Sibonga et al, 2019 ). Researchers have proposed that the current exercise devices available on the ISS could be augmented by a constant-resistance pulley to prevent atrophy of spinal muscle stabilizers ( Sayson et al, 2015 ).…”

Section: Microgravitymentioning

confidence: 99%

Crew-Friendly Countermeasures Against Musculoskeletal Injuries in Aviation and Spaceflight

et al. 2020

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Aviation and space medicine face many common musculoskeletal challenges that manifest in crew of rotary-wing aircraft (RWA), high-performance jet aircraft (HPJA), and spacecraft. Furthermore, many astronauts are former pilots of RWA or HPJA. Flight crew are exposed to recurrent musculoskeletal risk relating to the extreme environments in which they operate, including high-gravitational force equivalents (g-forces), altered gravitational vectors, vibratory loading, and interaction with equipment. Several countermeasures have been implemented or are currently under development to reduce the magnitude and frequency of these injuries. Cervical and lumbar spine, as well as extremity injuries, are common to aviators and astronauts, and occur in training and operational environments. Stress on the spinal column secondary to gravitational loading and unloading, ± vibration are implicated in the development of pain syndromes and intervertebral disk pathology. While necessary for operation in extreme environments, crew-support equipment can contribute to musculoskeletal strain or trauma. Crew-focused injury prevention measures such as stretching, exercise, and conditioning programs have demonstrated the potential to prevent pre-flight, in-flight, and post-flight injuries. Equipment countermeasures, especially those addressing helmet mass and center of gravity and spacesuit ergonomics, are also key in injury prevention. Furthermore, behavioral and training interventions are required to ensure that crew are prepared to safely operate when faced with these exposures. The common operational exposures and risk factors between RWA and HPJA pilots and astronauts lend themselves to collaborative studies to develop and improve countermeasures. Countermeasures require time and resources, and careful consideration is warranted to ensure that crew have access to equipment and expertise necessary to implement them. Further investigation is required to demonstrate long-term success of these interventions and inform flight surgeon decision-making about individualized treatment. Lessons learned from each population must be applied to the others to mitigate adverse effects on crew health and well-being and mission readiness.

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Resistive exercise in astronauts on prolonged spaceflights provides partial protection against spaceflight-induced bone loss

Cited by 89 publications

References 25 publications

Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight

Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight

Protective Effects of Controlled Mechanical Loading of Bone in C57BL6/J Mice Subject to Disuse

Crew-Friendly Countermeasures Against Musculoskeletal Injuries in Aviation and Spaceflight

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