Partial gravity unloading inhibits bone healing responses in a large animal model

Gadomski, Benjamin C.; McGilvray, Kirk C.; Easley, Jeremiah T.; Palmer, Ross H.; Santoni, Brandon G.; Puttlitz, Christian M.

doi:10.1016/j.jbiomech.2014.07.031

Cited by 20 publications

(29 citation statements)

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“…These models allow for control of fracture mechanics, reloading condition and environmental variables, providing important mechanistic information. While most studies have employed the rodent-based hindlimb unloading (HLU) model developed by Morey-Holton et al ., 80 other studies have employed larger animal models, 81 in which unilateral limb suspension was employed to evaluate the effect of unloading vs. loading on the rate and quality of fracture healing. Evidence from animal models supports the idea that chronic disuse associated with the spaceflight environment result in delayed fracture healing and compromise in the quality of the bone after healing.…”

Section: Musculoskeletal Injury In Long-duration Spaceflightmentioning

confidence: 99%

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: Musculoskeletal Injury In Long-duration Spaceflightmentioning

confidence: 99%

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

et al. 2017

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“…Following 4 weeks of healing, the ExFix and Control groups demonstrated statistically significant differences in mean four‐point bending stiffnesses. Mean (standard deviation) four‐point bending stiffness of the ExFix group was 48.9 N/mm (±47.8 N/mm), whereas that of the Control group was 213.3 N/mm (±36.3 N/mm) ( p < 0.05, SigmaPlot, Systat Software, Inc., San Jose, CA) . The corresponding moduli of elasticity for the ExFix and Control fracture gaps were computed to be 1.69 and 8.45 MPa, respectively, based on the four‐point bending FE analysis.…”

Section: Resultsmentioning

confidence: 99%

“…The effects of simulated hypogravity on bone remodeling and fracture healing were previously investigated in two large animal (sheep) studies . Animal use approval was granted by the Colorado State University Animal Care and Use Committee (Approval #11‐2938A).…”

Section: Methodsmentioning

confidence: 99%

“…Despite the limited number of studies directly investigating fracture healing in reduced gravitational loading environments, numerous ground‐based studies have examined the effect of fixation rigidity on subsequent fracture healing on Earth. A large number of these studies relied on external fixation devices that allowed predefined amounts of axial movement in order to investigate the magnitude of interfragmentary motion necessary to alter fracture healing in both animal models and human patient cohorts . It has also been demonstrated that rigid fixation has a deleterious impact on the fracture healing cascade while improved fracture healing occurred when axial micromotion is delivered to the fracture site .…”

mentioning

confidence: 99%

“…It has also been demonstrated that rigid fixation has a deleterious impact on the fracture healing cascade while improved fracture healing occurred when axial micromotion is delivered to the fracture site . While these studies provide valuable insight about the role fracture dynamization and interfragmentary movement of the fracture itself have on the healing process (as compared to static fixation techniques), fewer studies have investigated the direct role of fixation stiffness on in vivo fracture healing in a static environment . Gilbert et al investigated tibial fracture healing over 9 weeks in a canine model and observed no significant differences in failure force, stiffness, or energy to failure as a function of fixator stiffness .…”

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confidence: 99%

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Computational characterization of fracture healing under reduced gravity loading conditions

Gadomski

Lerner

Browning

et al. 2016

Journal Orthopaedic Research

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ABSTRACT:The literature is deficient with regard to how the localized mechanical environment of skeletal tissue is altered during reduced gravitational loading and how these alterations affect fracture healing. Thus, a finite element model of the ovine hindlimb was created to characterize the local mechanical environment responsible for the inhibited fracture healing observed under experimental simulated hypogravity conditions. Following convergence and verification studies, hydrostatic pressure and strain within a diaphyseal fracture of the metatarsus were evaluated for models under both 1 and 0.25 g loading environments and compared to results of a related in vivo study. Results of the study suggest that reductions in hydrostatic pressure and strain of the healing fracture for animals exposed to reduced gravitational loading conditions contributed to an inhibited healing process, with animals exposed to the simulated hypogravity environment subsequently initiating an intramembranous bone formation process rather than the typical endochondral ossification healing process experienced by animals healing in a 1 g gravitational environment. The literature is deficient with regard to the specific alterations in the localized mechanical environment of skeletal tissue during the reduced gravitational loading characteristic of spaceflight and how these alterations affect fracture healing in Haversian systems. Additionally, investigations that have attempted to link the direct role of these reduced gravitational forces to fracture healing have been limited primarily to rodent studies. [1][2][3][4] The in vivo studies that have been reported have consistently demonstrated that weight-bearing maintains skeletal integrity, and ultimately, accelerates the healing of long bone fractures by promoting rapid callus formation.5 However, the lack of mechanical loading experienced during weightlessness leads to the inhibition of fracture healing. [1][2][3][4] More specifically, these studies have demonstrated decreased chondrogenesis, mechanical strength, callus size, osteoblast activity, and bone formation rates in animals that healed in reduced loading environments as compared to those that healed in a full Earth gravity loading condition.1-4 Despite the limited number of studies directly investigating fracture healing in reduced gravitational loading environments, numerous ground-based studies have examined the effect of fixation rigidity on subsequent fracture healing on Earth. A large number of these studies relied on external fixation devices that allowed predefined amounts of axial movement in order to investigate the magnitude of interfragmentary motion necessary to alter fracture healing in both animal models and human patient cohorts. [6][7][8][9][10][11][12] It has also been demonstrated that rigid fixation has a deleterious impact on the fracture healing cascade while improved fracture healing occurred when axial micromotion is delivered to the fracture site. [13][14][15] While these studies provide valuable insight ab...

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Foot Surgery Viewed Through the Prism of Comparative Anatomy

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Partial gravity unloading inhibits bone healing responses in a large animal model

Cited by 20 publications

References 20 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

Computational characterization of fracture healing under reduced gravity loading conditions

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