Menu

 

Task Book: Biological & Physical Sciences Division and Human Research Program
Advanced Search     

Project Title:  Astronaut Bone Medical Standards Derived from Finite Element [FE] Modeling of QCT Scans from Populations Studies Reduce
Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/27/2012  
End Date: 09/30/2018  
Task Last Updated: 09/24/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Sibonga, Jean  Ph.D. / NASA Johnson Space Center 
Address:  Bone & Mineral Laboratory, SK 272 
2101 NASA Parkway 
Houston , TX 77058 
Email: jean.sibonga-1@nasa.gov 
Phone: 281-483-4556  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Orwoll, Eric  M.D. Oregon Health and Sciences University 
Amin, Shreyasee  M.D. Mayo Clinic 
Lang, Thomas  Ph.D. University of California, San Francisco 
Keyak, Joyce  Ph.D. University of California, Irvine 
Cody, Dianna  Ph.D. University of Texas MD Anderson Center 
Nicolella, Daniel  Ph.D. Southwest Research Institute 
Cheung, Angela  Ph.D., M.D. University Health Network / Toronto Rehabilitation Institute / Mount Sinai Hospital 
Key Personnel Changes / Previous PI: September 2018 report: For the final year of the project, former CoInvestigators (CoIs) Sundeep Khosla, M.D. and Tony Keaveny, Ph.D. are no longer CoIs.
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Ploeger, Stephanne  
Center Contact:  
stephanne.l.ploeger22@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
(2) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Fracture03:We need a validated method to estimate the risk of fracture by evaluating the ratio of applied loads to bone fracture loads for expected mechanically-loaded activities during a mission (IRP Rev E)
(2) Osteo01:A new acceptable bone health standard using an expanded surrogate for bone health needs to be defined for the flight environment (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Project had been extended some time ago to 9/30/2018, per PI (Ed., 9/24/18)

NOTE: Extended to 6/30/2016 per P. Baskin/HRP (Ed., 1/5/15)

NOTE: Extended to 12/30/2014, per M. Covington/ JSC HRP (Ed., 7/3/14)

NOTE: End date is 9/30/2014 per PI (Ed., 4/24/14)

NOTE: Gap changes per IRP Rev E (Ed., 1/27/14)

Task Description: A Research and Clinical Advisory Panel [RCAP] met in 2010 (Bone Summit) to review medical and research data of long-duration astronauts in order to make recommendations for the risk management for early onset osteoporosis in long duration astronauts. In its assessment, the RCAP stated that the guidelines using bone mineral density [BMD] T-scores as diagnostic criteria for osteoporosis have minimal clinical utility for the younger aged (< 50 years), predominantly male, astronaut cohort following exposure to prolonged spaceflight. In addition, NASA’s research data have revealed that DXA measurement of hip BMD does not capture all of the effects of spaceflight that influence bone strength (Keyak et al., Bone 2009; 44(3):449-53). The Bone Summit RCAP recommended that NASA explore emerging population studies that use hip bone strength, as estimated from Finite Element [FE] models of QCT [quantitative computed tomography] scans, to supplement DXA bone mineral density [BMD] as a combined standard for bone health (Orwoll et al., J Bone Miner Res 2013; 28(6):1243-1255). To this aim, the Bone Discipline Lead (named as Principal Investigator), convened a Task Group of US principal investigators and FE modelers of those QCT population studies, along with one non-advocate FE modeler, to propose a FEM-based method by which bone medical standards could be modified. The FE strength cutoffs that are generated by this proposed method will be reviewed, modified if required, and accepted for recommendation by the FE Task Group as a bone health medical standard specific for astronauts exposed to the spaceflight environment.

Specific Aims

NASA’s Bone medical standards establish the “operating bands for bone health” that: a) qualify an astronaut for long duration spaceflights, b) establish the non-permissible outcome for a spaceflight mission, c) provide a level of efficacy for countermeasures as well as d) screen for optimal bone health in an applicant for the astronaut corps. The current Bone medical standards are based upon the diagnostic criteria for a terrestrial population known to be at risk for osteoporosis, i.e., perimenopausal and postmenopausal women and men over the age of 50.

As a follow-up to the Bone Summit RCAP recommendation, the FE Task Group proposes the following Specific Aims to accomplish the task of generating of FE-based medical standards to supplement the existing BMD T-score-based standards:

1) Develop a dataset of FE hip strengths from human subjects, with ages covering the age range of the astronauts and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study (as authorized by Drs. Sundeep Khosla and Shreyasee Amin) will provide QCT scans from ~408 persons to Dr. Joyce Keyak who will develop FE models and estimate hip bone strength using the FE modeling developed at University of Califormia Irvine (Keyak JH, et al. Clin Orthop Relat Res. 2005 Aug;(437):219-28).

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans from additional study cohorts, which include International Space Station (ISS) astronauts.

2) Determine FE strength cutoffs, from Specific Aim 1b, to be used as a decision-tool by Space & Clinical Operations Division for the following scheduled decision points (a-d):

a. to qualify a sub-set of applicants for astronaut candidacy (those who currently are not qualified due to hip T-score between -1 and -1.5) for further medical testing

b. to qualify an astronaut for a long-duration (LD) mission

c. to qualify a veteran LD astronaut for a second LD mission

d. to establish responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present, review, and finalize the generated FE strength cutoffs with FE Task Group (along with the inclusion of cohort biostatisticians) to recommend to Human Health Countermeasures as a deliverable to the Space Medicine Space & Clinical Operations Division and Office of Chief Health and Medical Officer.

(Ed. note: revised version, per PI. 8/27/2013)

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal. Bone Medical standards provide the index by which the effects of spaceflight, the efficacy of countermeasures and the restoration of skeletal health following long-duration missions are all evaluated. Consequently, it is important and urgent to increase the sufficiency of our current bone medical standards in order not to risk underestimating the fracture or osteoporosis risks or the effectiveness and timing of strategies to mitigate the risk (e.g., in-flight countermeasures, selection criteria, flight certification). The Bone Summit RCAP of 2010, which made the recommendation to modify the BMD-based bone medical standards to be more relevant to the target population (i.e., long-duraiton astronauts), was composed of leaders in the International Society of Clinical Densitometry [ISCD] – This society formulates the positions by which BMD is used in clinical practice in terrestrial medicine and currently by the JSC Bone and Mineral Laboratory for Med Volume b and for required astronaut medical evaluation.

Research Impact/Earth Benefits: A successful demonstration will demonstrate how Finite Element Models could enhance the ability to determine fracture probability in terrestrial populations.

Task Progress & Bibliography Information FY2018 
Task Progress: Experiment Status

Specific Aims

1) Develop a dataset of FE hip strengths for subjects a) with ages covering the age range of the astronauts, and b) for which fractures outcome data have been collected. Completed. 12/03/13.

2) Review and evaluate dataset by FE Task Group members to suggest method(s) by which FE strength cutoffs from this dataset could be to supplement current areal BMD-based standards for the following:

a) a non-permissible outcome (POL) for hip bone strength after spaceflight to establish level of countermeasure efficacy,

b) an additional metric for screening bone health in applicants to the astronaut corps who fail to meet the bone medical standard of hip T-score>-1.0,

c) a fitness-for-flight standard in astronauts for a second long-duration mission, and

d) an index for assessing an astronaut’s risk for overloading the hip due to certain post-mission physical activities.

3) A manuscript of FE Task Group opinions (#2 above) will be prepared for concurrence by Task Group members and submitted for publication. Hip “Load Capacity” as Cut-points for Astronaut Skeletal Health: Recommendations of the NASA Finite Element (FE) Strength Task Group. Andrew S. Michalski , Shreyasee Amin MD , Angela M. Cheung MD , Dianna D. Cody PhD , Joyce H. Keyak PhD , Thomas F. Lang PhD , Daniel P. Nicolella PhD , Eric S. Orwoll MD , Steven K. Boyd PhD , Jean D. Sibonga PhD. Completed. 9/30/18 and manuscript awaiting approval for submission to npgMicrogravity.

Bibliography Type: Description: (Last Updated: 05/24/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Michalski AS, Feiveson AH, Lewandowski B, Amin S, Keyak J, Boyd SK, Sibonga JD. "A spaceflight bone deconditioning model for predicting mission-specific fracture risk." Canadian Orthopaedic Research Society Annual Meeting 2018, Victoria, BC, Canada, June 21, 2018.

Canadian Orthopaedic Research Society Annual Meeting 2018, Victoria, BC, Canada, June 21, 2018. , Jun-2018

Abstracts for Journals and Proceedings Michalski AS, Amin S, Keyak J, Lewandowski B, Boyd SK, Sibonga JD. "Long-duration astronaut QCT-FE as a biomechanical approach for probabilistic fracture risk assessment." Canadian Aeronautics and Space Institute 18th Astronautics Conference, Quebec City, QC, Canada, May 15-17, 2018.

Canadian Aeronautics and Space Institute 18th Astronautics Conference, Quebec City, QC, Canada, May 15-17, 2018. , May-2018

Articles in Peer-reviewed Journals Michalski AS, Amin S, Cheung AM, Cody DD, Keyak JH, Lang TF, Nicolella DP, Orwoll ES, Boyd SK, Sibonga JD. "Hip load capacity cut-points for Astronaut Skeletal Health NASA Finite Element Strength Task Group Recommendations." npgMicrogravity. 2019 Mar;5(1):6. https://doi.org/10.1038/s41526-019-0066-3 ; PubMed PMID: 30886891; PubMed Central PMCID: PMC6418107 , Mar-2019
NASA Technical Documents Sibonga JD, Truszkowski P. "Conference Proceedings -2010 Bone Summit: Risk for Early Onset Osteoporosis." Houston, TX: NASA Johnson Space Center, 2016. 40 p. NASA/TM-2016-219284. , Dec-2016
Project Title:  Astronaut Bone Medical Standards Derived from Finite Element [FE] Modeling of QCT Scans from Populations Studies Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/27/2012  
End Date: 06/30/2016  
Task Last Updated: 04/29/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Sibonga, Jean  Ph.D. / NASA Johnson Space Center 
Address:  Bone & Mineral Laboratory, SK 272 
2101 NASA Parkway 
Houston , TX 77058 
Email: jean.sibonga-1@nasa.gov 
Phone: 281-483-4556  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Orwoll, Eric  M.D. Oregon Health and Sciences University 
Khosla, Sundeep  M.D. Mayo Clinic 
Amin, Shreyasee  M.D. Mayo Clinic 
Lang, Thomas  Ph.D. University of California, San Francisco 
Keyak, Joyce  Ph.D. University of California, Irvine 
Keaveny, Tony  Ph.D. University of California Berkeley 
Cody, Dianna  Ph.D. University of Texas MD Anderson Center 
Nicolella, Daniel P Southwest Research Institute 
Cheung, Angela M University Health Network / Toronto Rehabilitation Institute / Mount Sinai Hospital 
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Ploeger, Stephanne  
Center Contact:  
stephanne.l.ploeger22@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
(2) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Fracture03:We need a validated method to estimate the risk of fracture by evaluating the ratio of applied loads to bone fracture loads for expected mechanically-loaded activities during a mission (IRP Rev E)
(2) Osteo01:A new acceptable bone health standard using an expanded surrogate for bone health needs to be defined for the flight environment (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Extended to 6/30/2016 per P. Baskin/HRP (Ed., 1/5/15)

NOTE: Extended to 12/30/2014, per M. Covington/ JSC HRP (Ed., 7/3/14)

NOTE: End date is 9/30/2014 per PI (Ed., 4/24/14)

NOTE: Gap changes per IRP Rev E (Ed., 1/27/14)

Task Description: A Research and Clinical Advisory Panel [RCAP] met in 2010 (Bone Summit) to review medical and research data of long-duration astronauts in order to make recommendations for the risk management for early onset osteoporosis in long duration astronauts. In its assessment, the RCAP stated that the guidelines using bone mineral density [BMD] T-scores as diagnostic criteria for osteoporosis have minimal clinical utility for the younger aged (< 50 years), predominantly male, astronaut cohort following exposure to prolonged spaceflight. In addition, NASA’s research data have revealed that DXA measurement of hip BMD does not capture all of the effects of spaceflight that influence bone strength (Keyak et al., Bone 2009; 44(3):449-53) The Bone Summit RCAP recommended that NASA explore emerging population studies that use hip bone strength, as estimated from Finite Element models of QCT [quantitative computed tomography] scans, to supplement DXA bone mineral density [BMD] as a combined standard for bone health (Orwoll et al. J Bone Miner Res 2013; 28(6):1243-1255). To this aim, the Bone Discipline Lead (named as PI), convened a Task Group of US principal investigators and FE modelers of those QCT population studies, along with one non-advocate FE modeler, to propose a FEM-based method by which bone medical standards could be modified. The FE strength cutoffs that are generated by this proposed method will be reviewed, modified if required, and accepted for recommendation by the FE Task Group as a bone health medical standard specific for astronauts exposed to the spaceflight environment.

Specific Aims

NASA’s Bone medical standards establish the “operating bands for bone health” that: a) qualify an astronaut for long duration spaceflights, b) establish the non-permissible outcome for a spaceflight mission, c) provide a level of efficacy for countermeasures as well as d) screen for optimal bone health in an applicant for the astronaut corps. The current Bone medical standards are based upon the diagnostic criteria for a terrestrial population known to be at risk for osteoporosis, i.e., perimenopausal and postmenopausal women and men over the age of 50.

As a follow-up to the Bone Summit RCAP recommendation, the FE Task Group proposes the following Specific Aims to accomplish the task of generating of FE-based medical standards to supplement the existing BMD T-score-based standards:

1) Develop a dataset of FE hip strengths from human subjects: with ages covering the age range of the astronauts and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study (as authorized by Drs. Sundeep Khosla and Shreyasee Amin) will provide QCT scans from ~408 persons to Dr. Joyce Keyak who will develop FE models and estimate hip bone strength using the FE modeling developed at UCI (Keyak, 2005).

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans from additional study cohorts, which include ISS astronauts.

2) Determine FE strength cutoffs, from Specific Aim 1b, to be used as a decision-tool by Space & Clinical Operations Division for the following scheduled decision points (a-d):

a. to qualify a sub-set of applicants for astronaut candidacy (those who currently are not qualified due to hip T-score between -1 and -1.5) for further medical testing

b. to qualify an astronaut for a long-duration (LD) mission

c. to qualify a veteran LD astronaut for a second LD mission

d. to establish responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present, review, and finalize the generated FE strength cutoffs with FE Task Group (along with the inclusion of cohort biostatisticians) to recommend to Human Health Countermeasures as a deliverable to the Space Medicine Space & Clinical Operations Division and Office of Chief Health and Medical Officer.

(Ed. note: revised version, per PI. 8/27/2013)

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal. Bone Medical standards provide the index by which the effects of spaceflight, the efficacy of countermeasures and the restoration of skeletal health following long-duration missions are all evaluated. Consequently, it is important and urgent to increase the sufficiency of our current bone medical standards in order not to risk underestimating the fracture or osteoporosis risks or the effectiveness and timing of strategies to mitigate the risk (e.g., in-flight countermeasures, selection criteria, flight certification). The Bone Summit RCAP of 2010, which made the recommendation to modify the BMD-based bone medical standards to be more relevant to the target population (i.e., long-duraiton astronauts), was composed of leaders in the International Society of Clinical Densitometry [ISCD] – This society formulates the positions by which BMD is used in clinical practice in terrestrial medicine and currently by the JSC Bone and Mineral Laboratory for Med Volume b and for required astronaut medical evaluation.

Research Impact/Earth Benefits: A successful demonstration will demonstrate how Finite Element Models could enhance the ability to determine fracture probability in terrestrial populations.

Task Progress & Bibliography Information FY2014 
Task Progress: The goals during FY 2013-2014:

1) Develop a dataset of FE hip strengths, of human subjects, that have all been generated by the same FE model; human subjects span ages of the astronauts population and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study provided QCT scans from 408 persons to Dr. Joyce Keyak who generated FE models from QCT data and estimated hip bone strength by FF model analysis that was developed at University of California at Irvine- UCI (Keyak, 2005). The contract with UCI was set up in June 2012 and this work was completed in December 2013.

b. FE data from 1a (above) were combined with FE data generated from other applications of Keyak FEM to QCT scans of cohorts from University of California at San Francisco -UCSF studies, which also included 13 ISS astronauts. The full FE Strength database is expected to be delivered in May 2014 following data cleaning.

2) FE strength cutoffs to be used for decision-making by Space & Clinical Operations Division will be determined, if feasible, by the using conventional biostatistical approaches (receiver operating characteristic [ROC] and Area Under the Curve), in order to determine the following decision points (below, a-d) –

a. Screening an applicant for astronaut candidacy

b. Qualifying an astronaut for a long-duration (LD) mission

c. Qualifying a previously-flown LD astronaut for a second LD mission

d. Understanding a causality for a post-mission fracture or osteoporosis diagnosis.

3) The generated FE strength cutoffs will be presented to FE Task Group II (with inclusion of a physician, FE modeler and cohort biostatisticians from UCSF, Mayo, and JSC) for review and possible refinement. The final FE strength cutoffs will be recommended to Human Health Countermeasures to process through Transition-to-Operations [TTO].

Bibliography Type: Description: (Last Updated: 05/24/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Keyak J, Kaneko T, Khosla S, Amin S. "Proximal Femoral Strengths in Men and Women Age 27 to 90+: A Subject-Specific Finite Element Modeling Study." 7th World Congress of Biomechanics, Boston, MA, July 6-11, 2014. Invited abstract.

7th World Congress of Biomechanics, Boston, MA, July 6-11, 2014. Program in press as of April 2014. http://wcb2014.com/ , Apr-2014

Project Title:  Astronaut Bone Medical Standards Derived from Finite Element [FE] Modeling of QCT Scans from Populations Studies Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/27/2012  
End Date: 12/30/2014  
Task Last Updated: 05/02/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Sibonga, Jean  Ph.D. / NASA Johnson Space Center 
Address:  Bone & Mineral Laboratory, SK 272 
2101 NASA Parkway 
Houston , TX 77058 
Email: jean.sibonga-1@nasa.gov 
Phone: 281-483-4556  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Orwoll, Eric  M.D. Oregon Health and Sciences University 
Khosla, Sundeep  M.D. Mayo Clinic 
Amin, Shreyasee  M.D. Mayo Clinic 
Lang, Thomas  Ph.D. University of California, San Francisco 
Keyak, Joyce  Ph.D. University of California, Irvine 
Keaveny, Tony  Ph.D. University of California Berkeley 
Cody, Dianna  Ph.D. University of Texas MD Anderson Center 
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
(2) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Fracture03:We need a validated method to estimate the risk of fracture by evaluating the ratio of applied loads to bone fracture loads for expected mechanically-loaded activities during a mission (IRP Rev E)
(2) Osteo01:A new acceptable bone health standard using an expanded surrogate for bone health needs to be defined for the flight environment (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Extended to 12/30/2014, per M. Covington/ JSC HRP (Ed., 7/3/14)

NOTE: End date is 9/30/2014 per PI (Ed., 4/24/14)

NOTE: Gap changes per IRP Rev E (Ed., 1/27/14)

Task Description: A Research and Clinical Advisory Panel [RCAP] met in 2010 (Bone Summit) to review medical and research data of long-duration astronauts in order to make recommendations for the risk management for early onset osteoporosis in long duration astronauts. In its assessment, the RCAP stated that the guidelines using bone mineral density [BMD] T-scores as diagnostic criteria for osteoporosis have minimal clinical utility for the younger aged (< 50 years), predominantly male, astronaut cohort following exposure to prolonged spaceflight. In addition, NASA’s research data have revealed that DXA measurement of hip BMD does not capture all of the effects of spaceflight that influence bone strength (Keyak et al., Bone 2009; 44(3):449-53) The Bone Summit RCAP recommended that NASA explore emerging population studies that use hip bone strength, as estimated from Finite Element models of QCT [quantitative computed tomography] scans, to supplement DXA bone mineral density [BMD] as a combined standard for bone health (Orwoll et al. J Bone Miner Res 2013; 28(6):1243-1255). To this aim, the Bone Discipline Lead (named as PI), convened a Task Group of US principal investigators and FE modelers of those QCT population studies, along with one non-advocate FE modeler, to propose a FEM-based method by which bone medical standards could be modified. The FE strength cutoffs that are generated by this proposed method will be reviewed, modified if required, and accepted for recommendation by the FE Task Group as a bone health medical standard specific for astronauts exposed to the spaceflight environment.

Specific Aims

NASA’s Bone medical standards establish the “operating bands for bone health” that: a) qualify an astronaut for long duration spaceflights, b) establish the non-permissible outcome for a spaceflight mission, c) provide a level of efficacy for countermeasures as well as d) qualify an applicant for the astronaut corps. The current Bone medical standards are based upon the diagnostic criteria for a terrestrial population known to be at risk for osteoporosis, i.e., perimenopausal and postmenopausal women and men over the age of 50.

As a follow-up to the Bone Summit RCAP recommendation, the FE Task Group proposes the following Specific Aims to accomplish the task of generating of FE-based medical standards:

1) Develop a dataset of FE hip strengths from human subjects: with ages covering the age range of the astronauts and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study (as authorized by Drs. Sundeep Khosla and Shreyasee Amin) will provide QCT scans from ~408 persons to Dr. Joyce Keyak who will develop FE models and estimate hip bone strength using the FE modeling developed at UCI (Keyak, 2005).

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans from additional study cohorts, which include ISS astronauts.

2) Determine FE strength cutoffs from to be used as a decision-tool by Space Medicine for the following scheduled decision points (a-d):

a. to qualify a sub-set of applicants for astronaut candidacy (those who currently are not qualified due to hip T-score between -1 and -1.5) for further medical testing

b. to qualify an astronaut for a long-duration (LD) mission

c. to qualify a veteran LD astronaut for a second LD mission

d. to establish responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present, review, and finalize the generated FE strength cutoffs with FE Task Group (along with the inclusion of cohort biostatisticians) to recommend to Human Health Countermeasures as a deliverable to Space Medicine and Office of Chief Health and Medical Officer.

(Ed. note: revised version, per PI. 8/27/2013)

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal. Bone Medical standards provide the index by which the effects of spaceflight, the efficacy of countermeasures and the restoration of skeletal health following long-duration missions are all evaluated. Consequently, it is important and urgent to increase the sufficiency of our current bone medical standards in order not to risk underestimating the fracture or osteoporosis risks or the effectiveness and timing of strategies to mitigate the risk (e.g., in-flight countermeasures, selection criteria, flight certification). The Bone Summit RCAP of 2010, which made the recommendation to modify the BMD-based bone medical standards to be more relevant to the target population (i.e., long-duraiton astronauts), was composed of leaders in the International Society of Clinical Densitometry [ISCD] – This society formulates the positions by which BMD is used in clinical practice in terrestrial medicine and currently by the JSC Bone and Mineral Laboratory for Med Volume b and for required astronaut medical evaluation.

Research Impact/Earth Benefits: A successful demonstration will showcase how Finite Element Models could enhance the ability to determine fracture probability in terrestrial populations.

Task Progress & Bibliography Information FY2013 
Task Progress: 1) Develop a dataset of FE hip strengths, of human subjects, that have all been generated by the same FE model; human subjects span ages of the astronauts population and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study will provide QCT scans from 408 persons to Dr. Joyce Keyak who will estimate hip bone strength using her developed FEM at UCI (Keyak, 2005). The contract with UCI was set up in June 2012 and this work is in progress.

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans of cohorts from UCSF studies, which include ISS astronauts. The full FE Strength database is expected to be complete in November 2013.

2) Determine FE strength cutoffs to be used for decision-making by Space Medicine for the following scheduled decision points (below, a-d) – using conventional biostatistical approaches (receiver operating characteristic [ROC] and area under the curve [AUC]) to be performed by NASA/JSC Biostatisticians and working with representatives of Space and Clinical Operations [SD]:

a. Qualifying an applicant for astronaut candidacy

b. Qualifying an astronaut for a long-duration (LD) mission

c. Qualifying a previously-flown LD astronaut for a second LD mission

d. Assuming responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present generated FE strength cutoffs to FE Task Group (with inclusion of cohort biostatisticians from UCSF, Mayo, and JSC) for review and possible modification. Recommend finalized FE strength cutoffs to Human Health Countermeasures to process through Transition-to-Operations [TTO].

Bibliography Type: Description: (Last Updated: 05/24/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Sibonga JD. (on behalf of Finite Element [FE] Strength Task Group.) "How do we develop medical standards for bone health that are relevant to spaceflight? Astronaut Bone Medical Standards Derived from Finite Element [FE] Models of QCT Scans from Population Studies." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2013

Articles in Peer-reviewed Journals Orwoll ES, Adler RA, Amin S, Binkley N, Lewiecki EM, Petak SM, Shapses SA, Sinaki M, Watts NB, Sibonga JD. "Skeletal health in long-duration astronauts: Nature, assessment and management recommendations from the NASA bone summit." J Bone Miner Res. 2013 Jun;28(6):1243-55. http://dx.doi.org/10.1002/jbmr.1948 ; PubMed PMID: 23553962 , Jun-2013
Articles in Peer-reviewed Journals Sibonga JD. "Spaceflight-induced bone loss: Is there an osteoporosis risk?" Curr Osteoporos Rep. 2013 Jun;11(2):92-8. http://dx.doi.org/10.1007/s11914-013-0136-5 ; PubMed PMID: 23564190 , Jun-2013
Project Title:  Astronaut Bone Medical Standards Derived from Finite Element [FE] Modeling of QCT Scans from Populations Studies Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/27/2012  
End Date: 06/30/2014  
Task Last Updated: 08/03/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Sibonga, Jean  Ph.D. / NASA Johnson Space Center 
Address:  Bone & Mineral Laboratory, SK 272 
2101 NASA Parkway 
Houston , TX 77058 
Email: jean.sibonga-1@nasa.gov 
Phone: 281-483-4556  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Orwoll, Eric  M.D. Oregon Health and Sciences University 
Khosla, Sundeep  M.D. Mayo Clinic 
Amin, Shreyasee  M.D. Mayo Clinic 
Lang, Thomas  Ph.D. University of California, San Francisco 
Keyak, Joyce  Ph.D. University of California, Irvine 
Keaveny, Tony  Ph.D. University of California Berkeley 
Cody, Dianna  Ph.D. University of Texas MD Anderson Center 
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
(2) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Fracture03:We need a validated method to estimate the risk of fracture by evaluating the ratio of applied loads to bone fracture loads for expected mechanically-loaded activities during a mission (IRP Rev E)
(2) Osteo01:A new acceptable bone health standard using an expanded surrogate for bone health needs to be defined for the flight environment (IRP Rev E)
Task Description: A Research and Clinical Advisory Panel [RCAP] met in 2010 (Bone Summit) to review medical and research data of long-duration astronauts in order to make recommendations for the risk management for early onset osteoporosis in long duration astronauts. In its assessment, the RCAP stated that the guidelines using bone mineral density [BMD] T-scores as diagnostic criteria for osteoporosis have minimal clinical utility for the younger aged (< 50 years), predominantly male, astronaut cohort following exposure to prolonged spaceflight. In addition, NASA’s research data have revealed that DXA measurement of hip BMD does not capture all of the effects of spaceflight that influence bone strength (Keyak et al., Bone 2009; 44(3):449-53) The Bone Summit RCAP recommended that NASA explore emerging population studies that use hip bone strength, as estimated from Finite Element models of QCT [quantitative computed tomography] scans, to supplement DXA bone mineral density [BMD] as a combined standard for bone health (Orwoll et al. J Bone Miner Res 2013; 28(6):1243-1255). To this aim, the Bone Discipline Lead (named as PI), convened a Task Group of US principal investigators and FE modelers of those QCT population studies, along with one non-advocate FE modeler, to propose a FEM-based method by which bone medical standards could be modified. The FE strength cutoffs that are generated by this proposed method will be reviewed, modified if required, and accepted for recommendation by the FE Task Group as a bone health medical standard specific for astronauts exposed to the spaceflight environment.

Specific Aims

NASA’s Bone medical standards establish the “operating bands for bone health” that: a) qualify an astronaut for long duration spaceflights, b) establish the non-permissible outcome for a spaceflight mission, c) provide a level of efficacy for countermeasures as well as d) qualify an applicant for the astronaut corps. The current Bone medical standards are based upon the diagnostic criteria for a terrestrial population known to be at risk for osteoporosis, i.e., perimenopausal and postmenopausal women and men over the age of 50.

As a follow-up to the Bone Summit RCAP recommendation, the FE Task Group proposes the following Specific Aims to accomplish the task of generating of FE-based medical standards:

1) Develop a dataset of FE hip strengths from human subjects: with ages covering the age range of the astronauts and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study (as authorized by Drs. Sundeep Khosla and Shreyasee Amin) will provide QCT scans from ~408 persons to Dr. Joyce Keyak who will develop FE models and estimate hip bone strength using the FE modeling developed at UCI (Keyak, 2005).

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans from additional study cohorts, which include ISS astronauts.

2) Determine FE strength cutoffs from to be used as a decision-tool by Space Medicine for the following scheduled decision points (a-d):

a. to qualify a sub-set of applicants for astronaut candidacy (those who currently are not qualified due to hip T-score between -1 and -1.5) for further medical testing

b. to qualify an astronaut for a long-duration (LD) mission

c. to qualify a veteran LD astronaut for a second LD mission

d. to establish responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present, review, and finalize the generated FE strength cutoffs with FE Task Group (along with the inclusion of cohort biostatisticians) to recommend to Human Health Countermeasures as a deliverable to Space Medicine and Office of Chief Health and Medical Officer.

(Ed. note: revised version, per PI. 8/27/2013)

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal. Bone Medical standards provide the index by which the effects of spaceflight, the efficacy of countermeasures and the restoration of skeletal health following long-duration missions are all evaluated. Consequently, it is important and urgent to increase the sufficiency of our current bone medical standards in order not to risk underestimating the fracture or osteoporosis risks or the effectiveness and timing of strategies to mitigate the risk (e.g., in-flight countermeasures, selection criteria, flight certification). The Bone Summit RCAP of 2010, which made the recommendation to modify the BMD-based bone medical standards to be more relevant to the target population (i.e., long-duraiton astronauts), was composed of leaders in the International Society of Clinical Densitometry [ISCD] – This society formulates the positions by which BMD is used in clinical practice in terrestrial medicine and currently by the JSC Bone and Mineral Laboratory for Med Volume b and for required astronaut medical evaluation.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2012 
Task Progress: New project for FY2012.

Bibliography Type: Description: (Last Updated: 05/24/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2012