Bone metabolism and renal stone risk during International Space Station missions

Smith, Scott M.; Heer, Martina; Shackelford, Linda; Sibonga, Jean D.; Spatz, Jordan; Pietrzyk, Robert A.; Hudson, Edgar K.; Zwart, Sara R.

doi:10.1016/j.bone.2015.10.002

Cited by 125 publications

(107 citation statements)

References 37 publications

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“…Studies of bone biochemistry of exercising subjects, both iRED and aRED, show increased levels of both bone resorption and formation during spaceflight. 16 aRED exercise tended to increase the level of bone formation markers without appreciably reducing the elevated resorption markers, which were attenuated only when anti-resorptive treatment is added to exercise. Thus, high-intensity resistance exercise shows strong evidence for substantially reducing the rate of bone loss in long-duration spaceflight as well as maintaining lean mass and physical condition.…”

Section: Bone and Muscle Loss: Evaluations In Spaceflightmentioning

confidence: 91%

Towards human exploration of space: the THESEUS review series on muscle and bone research priorities

et al. 2017

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Without effective countermeasures, the musculoskeletal system is altered by the microgravity environment of long-duration spaceflight, resulting in atrophy of bone and muscle tissue, as well as in deficits in the function of cartilage, tendons, and vertebral disks. While inflight countermeasures implemented on the International Space Station have evidenced reduction of bone and muscle loss on low-Earth orbit missions of several months in length, important knowledge gaps must be addressed in order to develop effective strategies for managing human musculoskeletal health on exploration class missions well beyond Earth orbit. Analog environments, such as bed rest and/or isolation environments, may be employed in conjunction with large sample sizes to understand sex differences in countermeasure effectiveness, as well as interaction of exercise with pharmacologic, nutritional, immune system, sleep and psychological countermeasures. Studies of musculoskeletal biomechanics, involving both human subject and computer simulation studies, are essential to developing strategies to avoid bone fractures or other injuries to connective tissue during exercise and extravehicular activities. Animal models may be employed to understand effects of the space environment that cannot be modeled using human analog studies. These include studies of radiation effects on bone and muscle, unraveling the effects of genetics on bone and muscle loss, and characterizing the process of fracture healing in the mechanically unloaded and immuno-compromised spaceflight environment. In addition to setting the stage for evidence-based management of musculoskeletal health in long-duration space missions, the body of knowledge acquired in the process of addressing this array of scientific problems will lend insight into the understanding of terrestrial health conditions such as age-related osteoporosis and sarcopenia.

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Section: Bone and Muscle Loss: Evaluations In Spaceflightmentioning

confidence: 91%

Towards human exploration of space: the THESEUS review series on muscle and bone research priorities

et al. 2017

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“…Finally, astronauts exposed to 4–6 months of weightlessness during missions to the International Space Station showed a 10–15% increase in circulating sclerostin levels despite regular use of an Advanced Resistance Exercise Device [86]. Based on these findings, both routine exercise and continuous exposure to gravity are likely important factors for regulating sclerostin levels.…”

Section: Systemic Regulation Of Sclerostinmentioning

confidence: 99%

Hormonal and systemic regulation of sclerostin

Drake

Khosla

2017

Bone

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The Wnt/β-catenin signaling pathway plays an essential role in osteoblast biology. Sclerostin is a soluble antagonist of Wnt/β-catenin signaling secreted primarily by osteocytes. Current evidence indicates that sclerostin likely functions as a local/paracrine regulator of bone metabolism rather than as an endocrine hormone. Nonetheless, circulating sclerostin levels in humans often reflect changes in the bone microenvironment, although there may be exceptions to this observation. Using existing assays, circulating sclerostin levels have been shown to be altered in response to both hormonal stimuli and across a variety of normal physiological and pathophysiological conditions. In both rodents and humans, parathyroid hormone provided either intermittently or continuously suppresses sclerostin levels. Likewise, most evidence from both human and animal studies supports a suppressive effect of estrogen on sclerostin levels. Efforts to examine non-hormonal/systemic regulation of sclerostin have in general shown less consistent findings or have provided associations rather than direct interventional information, with the exception of mechanosensory studies which have consistently demonstrated increased sclerostin levels with skeletal unloading, and conversely decreases in sclerostin with enhanced skeletal loading. Herein, we will review the existent literature on both hormonal and non-hormonal/systemic factors which have been studied for their impact on sclerostin regulation.

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“…With the disappearance of the 1 g gravity vector guidance, we hypothesized that bone structures built to resist mechanical loading will behave in accordance with their site (weight‐bearing/non‐weight‐bearing) and compartment (cortical/trabecular), with potentially diverse impacts on bone strength according to a long‐term pattern that remains unknown. We also assessed biochemical markers of bone remodeling, including the newly identified markers sclerostin, an inhibitor of osteoblastic bone formation, the expression of which was found to be increased during bed rest and tended to increase after spaceflight, and periostin, preferentially localized in cortical bone and the periosteum …”

Section: Introductionmentioning

confidence: 99%

Cortical and Trabecular Bone Microstructure Did Not Recover at Weight-Bearing Skeletal Sites and Progressively Deteriorated at Non-Weight-Bearing Sites During the Year Following International Space Station Missions

Vico

Rietbergen

Vilayphiou

et al. 2017

Journal of Bone and Mineral Research

104

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Risk for premature osteoporosis is a major health concern in astronauts and cosmonauts; the reversibility of the bone lost at the weight-bearing bone sites is not established, although it is suspected to take longer than the mission length. The bone three-dimensional structure and strength that could be uniquely affected by weightlessness is currently unknown. Our objective is to evaluate bone mass, microarchitecture, and strength of weight-bearing and non-weight-bearing bone in 13 cosmonauts before and for 12 months after a 4-month to 6-month sojourn in the International Space Station (ISS). Standard and advanced evaluations of trabecular and cortical parameters were performed using high-resolution peripheral quantitative computed tomography. In particular, cortical analyses involved determination of the largest common volume of each successive individual scan to improve the precision of cortical porosity and density measurements. Bone resorption and formation serum markers, and markers reflecting osteocyte activity or periosteal metabolism (sclerostin, periostin) were evaluated. At the tibia, in addition to decreased bone mineral densities at cortical and trabecular compartments, a 4% decrease in cortical thickness and a 15% increase in cortical porosity were observed at landing. Cortical size and density subsequently recovered and serum periostin changes were associated with cortical recovery during the year after landing. However, tibial cortical porosity or trabecular bone failed to recover, resulting in compromised strength. The radius, preserved at landing, unexpectedly developed postflight fragility, from 3 months post-landing onward, particularly in its cortical structure. Remodeling markers, uncoupled in favor of bone resorption at landing, returned to preflight values within 6 months, then declined farther to lower than preflight values. Our findings highlight the need for specific protective measures not only during, but also after spaceflight, because of continuing uncertainties regarding skeletal recovery long after landing. © 2017 American Society for Bone and Mineral Research.

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Bone metabolism and renal stone risk during International Space Station missions

Cited by 125 publications

References 37 publications

Towards human exploration of space: the THESEUS review series on muscle and bone research priorities

Towards human exploration of space: the THESEUS review series on muscle and bone research priorities

Hormonal and systemic regulation of sclerostin

Cortical and Trabecular Bone Microstructure Did Not Recover at Weight-Bearing Skeletal Sites and Progressively Deteriorated at Non-Weight-Bearing Sites During the Year Following International Space Station Missions

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