Last Published:  03/26/21 03:33:57 PM (Central)
Responsible Element: Human Health Countermeasures (HHC)
Status: Open
Description
Present State:  
 

Prolonged spaceflight and mission operations expose long-duration astronauts to a unique set of risk factors that contribute to a decline in bone strength (both bone mass and quality). Some of these factors (e.g., sub-optimal nutrition, disuse, gender) are known to contribute to osteoporosis here on earth. However, some putative factors (e.g., radiation, hypercapnia, duration of spaceflight) are novel and need further research to understand the contribution to skeletal changes and to the overall osteoporosis risk during long-term health. The primary contributor to skeletal changes during spaceflight is presumably the reduced mechanical load to the skeleton (skeletal disuse) due both to weightlessness and muscle atrophy. Additionally, space travel introduces an array of risk factors (perturbed vitamin D metabolism, reduced exercise activity, reduced calcium absorption, sarcopenia) that are induced because of mission operations in the extreme space environment. Osteoporosis is a syndrome with multiple pathophysiologies. With the large number of risk factors for bone changes during spaceflight it would be time efficient to understand which risk factors are the most critical for mitigation and which risk factors can actually be modified, ideally by current, clinically-validated interventions. This gap generates knowledge (possibly across physiological systems) that can be used to prioritize the targets for overall risk mitigation. The goal is to provide the most essential information for a research & clinical advisory panel to develop clinical practice guidelines [CPGs] (Kanis et al, Osteoporos Int. 2007 18(8):1033-1046).


 
Interim Metrics (Sequential):
  1. Determine which known and putative risk factors induce significant changes in areal Bone Mineral Density (BMD) (of long duration astronauts) during spaceflight and with recovery, relative to a non-flying terrestrial population. In spite of the limitations in DXA technology, areal BMD can contribute up to 50-70% of bone strength.  Closure (high priority risk factors to target) will be recommended by a Research and Clinical Advisory Panel (RCAP) which is charged with advising NASA on how to respond clinically to biomedical data (#2). (20%)
  2. Convene RCAP on triennial basis to review data with the aim to identify and recommend a) which risk factors from #1) should be modified to mitigate the risk for early onset osteoporosis, b) which risk factors should continue to be monitored only and c) which interventions are recommended to modify critical risk factors. This identification is based upon Expert Opinion following review of all bone relevant data (measured musculoskeletal outcomes, risk factor data, epidemiological analyses etc.)(20%)
  3. Submit recommendation from #2 to the Human System Risk Board [HSRB] for disposition of research or mitigation strategies. (5%)
  4. Optimally mitigate the incidence of non-permissible outcome in long-duration astronauts by addressing, individualized to crewmember, a specific suite of critical risk factors. (55%)


Approach: 
Various epidemiological and biostatistical methods could be applied to evaluate a spaceflight-induced risk factor on aBMD decline in long-duration astronauts.  Models based upon aBMD are likely to be more robust because of the abundance of epidemiological data (linking aBMD to fracture outcomes) that is currently available and aBMD’s long-time acceptance as a predictor of hip and spine fracture.   

Overall, any proposed approach for analysis, by intramural or extramural investigators, should not only be reviewed for scientific merit, but also for clinical relevance; an expert panel knowledgeable in bone epidemiology and clinical trials could evaluate the contribution of risk factors to osteoporosis or to fracture risks.  An alternative approach is to develop a “Hybrid” Directed Research Task, e.g., NASA personnel executing an extramurally-designed collaborative study.  This approach would facilitate analysis of protected astronaut medical and research data by bone epidemiology experts in the extramural community.   In addition, preclinical (animal) studies can be designed to model risk factors and mission scenarios to which astronauts are exposed, e.g.,   repeat missions, prolonged missions, nutrition/dietary deficiencies, radiation, physical activity, aging, timing of intervention application (pre-, in-, postflight). Statistical power to compare changes in bone parameters (e.g., bone mass, bone strength, bone structure) in mechanically unloaded animals vs. animals that are weight-bearing may also be greater.  The effective implementation of animal models would provide preliminary research to inform the designs of clinical studies and/or serve as a surrogate for studies that cannot be safely conducted in humans
Target for Closure
Selected set of critical Risk Factors during and/or after spaceflight, to target for intervention (mitigate or eliminate) in order to address the risk for early onset osteoporosis.
Mappings
Risk Risk of Bone Fracture due to Spaceflight-induced Changes to Bone
You are here! Gap Osteo 4: We don't know the contribution of each risk factor on bone loss and recovery of bone strength, and which factors are the best targets for countermeasure application.
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