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Gap Osteo 6: How do skeletal changes due to spaceflight modify the terrestrial risk of osteoporotic fractures?
Last Published:  07/30/21 01:05:31 PM (Central)
Responsible Element: Human Health Countermeasures (HHC)
Status: Open
Description
Initial/Present State:

Osteoporosis is a medical condition of the skeleton that is characterized by low bone mass and severe structural deterioration which increases the probability of a fragility fracture (i.e., fracture due to minimal or no trauma).  The hip and the spine are common skeletal sites for fragility fractures in the aged because of an accumulated, lifetime exposure to risk factors associated with loss of bone mass and quality. To paraphrase the National Bone Health Coalition, osteoporosis is not a geriatric condition but a geriatric manifestation. It is unknown if exposure to spaceflight is a risk factor for inducing an earlier onset of osteoporosis in astronauts.  According to a panel of osteoporosis experts (Orwoll et al., JBMR 2013) and the Institute of Medicine (IOM) review of the Human Research Program (HRP) Evidence Book, there is enough indirect evidence to suggest that long-duration astronauts may develop premature osteoporosis. Notably, the gold standard method for validating a bone measure as a predictor of osteoporotic fractures, or an intervention as a mitigator of fracture risk, is to conduct a prospective population study of fracture outcome. NASA does not have the time or resources to acquire this level of evidence for it to be of any therapeutic benefit to the astronauts themselves. A clinical advisory panel (Orwoll et al., JBMR 2013) provided recommendations for the surveillance of bone health in long-duration astronauts; the aim was to generate data of sufficient quality to counterbalance the limited number of astronauts to describe the effects of spaceflight.  Following its review of trends in bone mineral density data from long-duration astronauts, the panel, in its opinion, agreed that an intervention may be required to prevent premature fragility fractures.  However, due to the inability of the data to reflect the full effects of spaceflight on fracture risk, the panel could not recommend the type or timing of mitigating strategies.  The goal of this gap is to monitor skeletal changes in the astronaut due to spaceflight, in the context of skeletal changes due to aging, to evaluate if changes due to spaceflight are irreversible and thus can combine with the expected changes due to aging. The Bone Summit Panel had recommended the implementation of Quantitative Computed Tomography (QCT) modality for risk surveillance because of its expanded evaluation of spaceflight effects on the hip, which include changes to volumetric Bone Mineral Densities (BMDs) of hip sub-regions (cortical and trabecular bone compartments) and of whole hip bone geometry.  Moreover, these conventional QCT measurements have been validated as predictors of hip fracture in elderly men and women (Gap Osteo 3). The expanded description of bone by QCT can be used further to generate Finite Element Models which can be analyzed to estimate hip bone strength for specific orientations of mechanical loading to the hip. Finally, the QCT modality enables detection of a clinical trigger (identified by the Bone Summit Panel, as the failure of detect recovery of hip trabecular volumetric BMD by two years after return to Earth from a typical 6-month mission on the ISS). To this aim, the Bone Summit Panel shall be reconvened on a triennial basis to review the accumulated medical and research data (as a Research & Clinical Advisory panel [RCAP] etc.) and to ensure that QCT is sufficiently monitoring bone structural changes (with spaceflight, with in-flight countermeasures, and with re-ambulation on Earth) to assess the restoration to preflight status or the requirement for an intervention.  Overall, the QCT surveillance of hip adaptation in the astronaut, in combination with QCT measures reported in aging population, will provide additional data to assess the likelihood of astronauts developing premature osteoporosis. 

Interim Stages/Metrics (Sequential): 

  1. Recommend implementation of Quantitative Computed Tomography (QCT) hip scanning for surveillance of long-duration (LD) astronauts to assess for clinical trigger at R+2 years. (25%)
  2. Develop & recommend implementation of a surveillance protocol for retired LD astronauts. (10%)
  3. Continue surveillance protocol with dual-energy x-ray absorptiometry (DXA) modality. (10%)
  4. Modify bone medical standards, as required, with additional data relating changes in Finite Element (FE) strength with spaceflight (from Hip QCT study). (10%)
  5. Apply a Probabilistic Risk Assessment [PRA] module (Nelson et al, Ann Biomedical Eng, 2009) to assess the probability of fracture based upon the mechanical loads and the frequency mechanically-loaded events.Assess fracture probability for design reference mission, for after return to Earth. (35%)
  6. Convene and obtain recommendation from Research and Clinical Advisory Panel (RCAP) for mitigation type and timing (certify, prevent, treat, rehabilitate) based on review of PRA outcomes and surveillance data. (10%)


Approach:

To counterbalance the constraints with and limitations of data acquisition from long-duration astronauts, the clinical advisory Bone Summit Panel suggested that research technologies and analyses should be applied to astronauts as part of an occupational risk surveillance program. The Surveillance Program should expand the description of changes to bone due to spaceflight beyond the measurement of bone mineral density by DXA technology.  If surveillance data indicate an irreversible decline in strength by two years after return, even in the absence of a diagnosis for osteoporosis, the changes due to spaceflight may combine with expected declines due to aging thereby predisposing the astronaut to an earlier onset of osteoporosis.  Gaps Osteo 2, Osteo 3, Osteo 4 and Osteo 5 represent the generation of novel research data to capture the unique effects of spaceflight.  The Bone Summit Panel will re-convene on a triennial basis to review the data generated by Osteo 2-5. This panel of clinical osteoporosis experts is skilled enough to evaluate the unique dataset and express expert opinion on whether there is an increased risk in astronauts based upon the probabilistic risk assessments [PRA] (Nelson et al, Ann Biomedical Eng, 2009).
Target for Closure
Validated prediction method for early onset osteoporotic fractures in astronauts.
Mappings
Risk Risk of Bone Fracture due to Spaceflight-induced Changes to Bone
You are here! Gap Osteo 6: How do skeletal changes due to spaceflight modify the terrestrial risk of osteoporotic fractures?
Active
Task Dose-Response Study of Musculoskeletal Outcomes Following Centrifugation in Adult Mice on ISS (Bouxsein)
Task Time Course of Spaceflight-Induced Adaptations in Bone Morphology, Bone Strength and Muscle Quality (Bouxsein)
Completed
Completed Task Combined Scanning Confocal Ultrasound Diagnostic and Treatment System for Bone Quality Assessment and Fracture Healing
Terminated
Task Vertebral Compression Fracture Assessment

Multi-Disciplinary Research Plans

Documentation:
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