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Project Title:  Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long Duration Space Flight Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/01/2008  
End Date: 11/30/2016  
Task Last Updated: 07/02/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Amin, Shreyasee  M.D. / Mayo Clinic College of Medicine 
Address:  200 First Street SW 
 
Rochester , MN 55905 
Email: amin.shreyasee@mayo.edu 
Phone: 507-284-4277  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mayo Clinic College of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Sibonga, Jean  Ph.D. NASA Johnson Space Center 
Key Personnel Changes / Previous PI: Dr. Sundeep Khosla was removed from the study in the fall of 2010.
Project Information: Grant/Contract No. NNX08AQ20G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NNX08AQ20G 
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) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Osteo04:We do not 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 (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date showing as 11/30/2016 per NSSC information (Ed., 5/3/17)

NOTE: Extended to 7/31/2016 per NSSC information (Ed., 4/19/16)

NOTE: Extended to 7/31/2015 per J. Sibonga/JSC and NSSC information (Ed., 7/16/14)

NOTE: Risk/Gap changes per IRP Rev E (Ed., 3/14/14)

NOTE: End date is 7/31/2014, per NSSC information (Ed., 8/9/13)

NOTE: End date changed to 7/31/2013 per NSSC information (Ed., 7/16/2012)

NOTE: End date changed to 7/31/2012 per C. Guidry/JSC (2/7/2011)

NOTE: Period of performance changed to 8/1/2008-7/31/2011 (from 5/20/08-5/19/11) per C. Guidry/JSC (3/2010)

Task Description: Bone loss is estimated to occur at a rate of 1% per month in space (microgravity), particularly in weight-bearing bones in the legs and spine. This rate of loss is equivalent to what we might lose in a year with advancing age on Earth. It remains unknown what this loss signifies for future fracture risk in crewmembers. While unloading of the skeleton in the weightless environment of space is considered the key factor contributing to bone loss, there are likely other factors that also play a role. Current prevention strategies have not been effective at preventing this bone loss. Improved understanding on the risk for fracture following long-duration space flight, as well as the factors contributing to bone loss in microgravity, and its recovery, are needed in order to develop better prevention strategies for the benefit of crew health, both during and after long-duration space exploration, and mission success.

The proposed research will take advantage of an established population-based cohort, which includes men and women of an age range similar to crewmembers in the U.S. space program, who have had bone density measured over time. We will make comparisons between bone densities of crewmembers and the population-based data and use fracture prediction models derived from the cohort to make estimations on fracture risk among crewmembers. We will also explore the data already gathered to date during the U.S. human space program in order to summarize the current state of evidence available on additional risk factors related to bone loss and recovery in microgravity. The ultimate goal of this research proposal is to provide evidence-based information which may assist in guiding the direction of further research required to better understand the risk of bone loss and fracture among crewmembers and the strategies that could be developed to prevent it from occurring.

Research Impact/Earth Benefits: This work will help establish the occupational risk of short and long-duration microgravity exposure on longterm bone health consequences among U.S. crewmembers. It will also serve to provide a comprehensive summary of the current evidence available on risk factors related to bone loss and recovery among U.S. crewmembers following long-duration space flight.

Task Progress & Bibliography Information FY2015 
Task Progress: [Ed. note: compiled in July 2019 from PI report submitted to JSC Human Research Program in 2015 covering period through July 2015. Note also that some publications after July 2015 have been added to Bibliography section in case no further report received.]

SPECIFIC AIMS:

AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk.

AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.

Overview of Findings Related to AIM 2 (Ed. note 7/1/19: see FY2013 report for AIM 1 findings): To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.

Data assembly at NASA-Johnson Space Center (JSC) on risk factors known to be related to bone loss and fracture risk was completed in early 2012. We have now performed analyses on these available data to help better understand the variability in hip bone mineral density (BMD) loss and recovery, post-flight. Risk factor data include, but are not limited to, medication use, bone turnover markers, and surrogates of exercise status in-flight, such as changes in strength measures, and lean muscle mass. Data assembly and data cleaning were completed. We noted that there were limited data on risk factors available beyond the initial return post long-duration flights, so analyses are restricted to the immediate post-flight period.

Following review of all the different measures available for analyses, we identified several different risk factors which may help identify those at greatest risk for bone loss during long-duration missions. These included pre-flight measures of elevated bone resorption, as well as surrogate markers of better muscle strength and greater aerobic capacity pre-flight. Our results suggest that individuals with high bone resorption markers preflight may benefit most from anti-resorptive therapy before a long-duration mission. Our findings also suggest that those who are the most physically fit preflight may have bones that have adapted to greater than average loading stimuli and therefore may be more susceptible to enhanced bone resorption once unloaded in microgravity, reinforcing the importance of maintaining adequate physical conditioning during long-duration spaceflight. Of note, our results are from data largely prior to US crewmembers having access to the advanced resistive exercise device (ARED), which may have helped overcome this important risk factor. Manuscripts are in preparation summarizing our findings for peer-reviewed publication.

Abstracts relating to preliminary analyses from this work have been presented at the annual meetings of the American Society of Bone and Mineral Research, American College of Rheumatology, International Academy of Astronautics Humans in Space Symposium, Aerospace Medical Association.

Bibliography Type: Description: (Last Updated: 07/01/2019)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Farr JN, Melton LJ 3rd, Achenbach SJ, Atkinson EJ, Khosla S, Amin S. "Fracture incidence and characteristics in young adults aged 18 to 49 years: A population-based study." J Bone Miner Res. 2017 Dec;32(12):2347-54. Epub 2017 Oct 3. https://doi.org/10.1002/jbmr.3228 ; PubMed PMID: 28972667; PubMed Central PMCID: PMC5732068 , Dec-2017
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." NPJ Microgravity. 2019 Mar 14;5:6. eCollection 2019. https://doi.org/10.1038/s41526-019-0066-3 ; PubMed PMID: 30886891; PubMed Central PMCID: PMC6418107 , Mar-2019
Project Title:  Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long Duration Space Flight Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/01/2008  
End Date: 11/30/2016  
Task Last Updated: 06/03/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Amin, Shreyasee  M.D. / Mayo Clinic College of Medicine 
Address:  200 First Street SW 
 
Rochester , MN 55905 
Email: amin.shreyasee@mayo.edu 
Phone: 507-284-4277  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mayo Clinic College of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Sibonga, Jean  NASA-Johnson Space Center 
Key Personnel Changes / Previous PI: Dr. Sundeep Khosla was removed from the study in the fall of 2010.
Project Information: Grant/Contract No. NNX08AQ20G 
Responsible Center: NASA JSC 
Grant Monitor: Ploeger, Stephanne  
Center Contact:  
stephanne.l.ploeger22@nasa.gov 
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NNX08AQ20G 
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) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Osteo04:We do not 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 (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date showing as 11/30/2016 per NSSC information (Ed., 5/3/17)

NOTE: Extended to 7/31/2016 (previously 7/31/2015) per NSSC information (Ed., 4/19/16)

NOTE: Extended to 7/31/2015 per J. Sibonga/JSC and NSSC information (Ed., 7/16/14)

NOTE: Risk/Gap changes per IRP Rev E (Ed., 3/14/14)

NOTE: End date is 7/31/2014, per NSSC information (Ed., 8/9/13)

NOTE: End date changed to 7/31/2013 per NSSC information (Ed., 7/16/2012)

NOTE: End date changed to 7/31/2012 per C. Guidry/JSC (2/7/2011)

NOTE: Period of performance changed to 8/1/2008-7/31/2011 (from 5/20/08-5/19/11) per C. Guidry/JSC (3/2010)

Task Description: Bone loss is estimated to occur at a rate of 1% per month in space (microgravity), particularly in weight-bearing bones in the legs and spine. This rate of loss is equivalent to what we might lose in a year with advancing age on Earth. It remains unknown what this loss signifies for future fracture risk in crewmembers. While unloading of the skeleton in the weightless environment of space is considered the key factor contributing to bone loss, there are likely other factors that also play a role. Current prevention strategies have not been effective at preventing this bone loss. Improved understanding on the risk for fracture following long-duration space flight, as well as the factors contributing to bone loss in microgravity, and its recovery, are needed in order to develop better prevention strategies for the benefit of crew health, both during and after long-duration space exploration, and mission success.

The proposed research will take advantage of an established population-based cohort, which includes men and women of an age range similar to crewmembers in the U.S. space program, who have had bone density measured over time. We will make comparisons between bone densities of crewmembers and the population-based data and use fracture prediction models derived from the cohort to make estimations on fracture risk among crewmembers. We will also explore the data already gathered to date during the U.S. human space program in order to summarize the current state of evidence available on additional risk factors related to bone loss and recovery in microgravity. The ultimate goal of this research proposal is to provide evidence-based information which may assist in guiding the direction of further research required to better understand the risk of bone loss and fracture among crewmembers and the strategies that could be developed to prevent it from occurring.

Research Impact/Earth Benefits: This work will help establish the occupational risk of short and long-duration microgravity exposure on longterm bone health consequences among U.S. crewmembers. It will also serve to provide a comprehensive summary of the current evidence available on risk factors related to bone loss and recovery among U.S. crewmembers following long-duration space flight.

Task Progress & Bibliography Information FY2013 
Task Progress: Overview of Year 5

As investigators external to NASA, there have been several different data access issues which posed a challenge to progress on work over the years. Over the period of the grant and no-cost extensions, we worked with our collaborators at NASA to overcome most issues, including the need to re-consent Mir crew for use of their data, which was completed at the end of 2011. Data assembly at NASA-JSC required for the study was completed by early 2012. Data cleaning and analyses are now underway related to Study Aims.

Progress Related to AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk. .

We have 100% participation rate of all U.S. crewmembers who have flown on at least one long-duration space mission on Mir or ISS as of December 2010 and had a post-flight bone density measured. We have 85% participation rate among U.S. crewmembers who have flown on short-duration space missions.

A manuscript is in preparation on the age- and gender-expected prediction models for bone mineral density (BMD) loss which were derived from the Mayo population-based cohort of 348 men (age range at baseline: 22-90 years) and 351 women (range: 21-93 years) and then applied to the NASA cohort of long-duration U.S. crewmembers. Our findings indicate that 6-18 months after returning from a long-duration flight, BMD at most sites was still lower than predicted in men, but not in women. In analyses of men who had follow-up to 3 years after return from their long-duration flight, BMD at most sites was now closer to predicted except for the hip where it was still significantly lower.

In analyses involving U.S. crew who have only served on short-duration missions in space, our results suggest that there do not appear to be any long-term negative effects of short duration space.flight on bone density in women or, at most sites, in men.

Progress Related to AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery, and fracture following long-duration space exploration.

Data assembly at NASA-JSC on risk factors known to be related to bone loss and fracture risk was completed in early 2012. We plan to use these data to help better understand the variability in BMD loss and recovery, post-flight. Risk factor data include, but are not limited to, medication use, bone turnover markers, and surrogates of exercise status in-flight, such as changes in strength measures, and lean muscle mass. Data assembly is now complete and data cleaning is ongoing. We note that limited data on risk factors are available beyond the initial return post long-duration flights. Analyses are currently underway.

Bibliography Type: Description: (Last Updated: 07/01/2019)  Show Cumulative Bibliography Listing
 
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." Journal of Bone and Mineral Research. 2013 Jun;28(6):1243-55. http://dx.doi.org/10.1002/jbmr.1948 ; PubMed PMID: 23553962 , Jun-2013
Project Title:  Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long Duration Space Flight Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/01/2008  
End Date: 07/31/2013  
Task Last Updated: 08/16/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Amin, Shreyasee  M.D. / Mayo Clinic College of Medicine 
Address:  200 First Street SW 
 
Rochester , MN 55905 
Email: amin.shreyasee@mayo.edu 
Phone: 507-284-4277  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mayo Clinic College of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Sibonga, Jean  NASA-Johnson Space Center 
Key Personnel Changes / Previous PI: Dr. Sundeep Khosla was removed from the study in the fall of 2010.
Project Information: Grant/Contract No. NNX08AQ20G 
Responsible Center: NASA JSC 
Grant Monitor: Maher, Jacilyn  
Center Contact:  
jacilyn.maher56@nasa.gov 
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NNX08AQ20G 
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) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Osteo04:We do not 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 (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date changed to 7/31/2013 per NSSC information (Ed., 7/16/2012)

NOTE: End date changed to 7/31/2012 per C. Guidry/JSC (2/7/2011)

NOTE: Period of performance changed to 8/1/2008-7/31/2011 (from 5/20/08-5/19/11) per C. Guidry/JSC (3/2010)

Task Description: Bone loss is estimated to occur at a rate of 1% per month in space (microgravity), particularly in weight-bearing bones in the legs and spine. This rate of loss is equivalent to what we might lose in a year with advancing age on Earth. It remains unknown what this loss signifies for future fracture risk in crewmembers. While unloading of the skeleton in the weightless environment of space is considered the key factor contributing to bone loss, there are likely other factors that also play a role. Current prevention strategies have not been effective at preventing this bone loss. Improved understanding on the risk for fracture following long-duration space flight, as well as the factors contributing to bone loss in microgravity, and its recovery, are needed in order to develop better prevention strategies for the benefit of crew health, both during and after long-duration space exploration, and mission success.

The proposed research will take advantage of an established population-based cohort, which includes men and women of an age range similar to crewmembers in the U.S. space program, who have had bone density measured over time. We will make comparisons between bone densities of crewmembers and the population-based data and use fracture prediction models derived from the cohort to make estimations on fracture risk among crewmembers. We will also explore the data already gathered to date during the U.S. human space program in order to summarize the current state of evidence available on additional risk factors related to bone loss and recovery in microgravity. The ultimate goal of this research proposal is to provide evidence-based information which may assist in guiding the direction of further research required to better understand the risk of bone loss and fracture among crewmembers and the strategies that could be developed to prevent it from occurring.

Research Impact/Earth Benefits: This work will help establish the occupational risk of short and long-duration microgravity exposure on longterm bone health consequences among U.S. crewmembers. It will also serve to provide a comprehensive summary of the current evidence available on risk factors related to bone loss and recovery among U.S. crewmembers following long-duration space flight.

Task Progress & Bibliography Information FY2012 
Task Progress: Overview of Year 4

As investigators external to NASA, there have been several different data access issues which have posed a challenge to progress on work over the years. However, we have worked with our collaborators at NASA and have been gradually able to overcome most issues. During this first no-cost-extension, comprehensive risk factors known to be related to bone health continued to be assembled at NASA-JSC and work was essentially complete as of early 2012. At Mayo, manuscripts are near completion related to sub-aims in Aim 1. Work on these analyses was delayed until we were able to re-consent Mir crew for use of their data, as required by NASA CPHS. Their bone density data had been collected under a research program, so it was determined that re-consent would be required, and this was completed at the end of 2011. Fracture prediction models have been developed using the Mayo cohort and we continue to work on models. Analyses are underway related to Aim 2.

Progress Related to AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk.

Re-consent of all Mir crew was obtained, so we continue to have 100% participation rate of all U.S. crewmembers who have flown on at least one long-duration space mission on Mir or ISS as of December 2010 and had a post-flight bone density measured. We have 85% participation rate among U.S. crewmembers who have flown on short-duration space missions.

A manuscript is in preparation on the age- and gender-expected prediction models for bone mineral density (BMD) loss which were derived from the Mayo population-based cohort of 348 men (age range at baseline: 22-90 years) and 351 women (range: 21-93 years) and then applied to the NASA cohort of long-duration U.S. crewmembers. Our findings indicate that 6-18 months after returning from a long-duration flight, BMD at most sites was still lower than predicted in men, but not in women. In further analyses of men who had follow-up to 3 years after return from their long-duration flight, BMD at most sites was now closer to predicted except for the hip where it was still significantly lower.

In analyses involving U.S. crew who have only served on short-duration missions in space, our results suggest that there do not appear to be any long-term negative effects of short duration spaceflight on bone density in women or, at most sites, in men.

Progress Related to AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.

Data assembly at NASA-JSC on risk factors known to be related to bone loss and fracture risk was completed by early 2012. We will use these data to help better understand the variability in BMD loss and recovery, post-flight. Risk factor data include, but are not limited to, medication use, bone turnover markers, and surrogates of exercise status in-flight, such as changes in strength measures, and lean muscle mass. Data assembly is complete. Data cleaning is ongoing. Descriptive analyses are currently underway.

Bibliography Type: Description: (Last Updated: 07/01/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2012
Project Title:  Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long Duration Space Flight Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/01/2008  
End Date: 07/31/2013  
Task Last Updated: 06/02/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Amin, Shreyasee  M.D. / Mayo Clinic College of Medicine 
Address:  200 First Street SW 
 
Rochester , MN 55905 
Email: amin.shreyasee@mayo.edu 
Phone: 507-284-4277  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mayo Clinic College of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Sibonga, Jean  NASA-Johnson Space Center 
Key Personnel Changes / Previous PI: Dr. Sundeep Khosla was removed from the study in the fall of 2010.
Project Information: Grant/Contract No. NNX08AQ20G 
Responsible Center: NASA JSC 
Grant Monitor: Baumann, David  
Center Contact:  
david.k.baumann@nasa.gov 
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NNX08AQ20G 
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) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Osteo04:We do not 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 (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date changed to 7/31/2013 per NSSC information (Ed., 7/16/2012)

NOTE: End date changed to 7/31/2012 per C. Guidry/JSC (2/7/2011)

NOTE: Period of performance changed to 8/1/2008-7/31/2011 (from 5/20/08-5/19/11) per C. Guidry/JSC (3/2010)

Task Description: Bone loss is estimated to occur at a rate of 1% per month in space (microgravity), particularly in weight-bearing bones in the legs and spine. This rate of loss is equivalent to what we might lose in a year with advancing age on Earth. It remains unknown what this loss signifies for future fracture risk in crewmembers. While unloading of the skeleton in the weightless environment of space is considered the key factor contributing to bone loss, there are likely other factors that also play a role. Current prevention strategies have not been effective at preventing this bone loss. Improved understanding on the risk for fracture following long-duration space flight, as well as the factors contributing to bone loss in microgravity, and its recovery, are needed in order to develop better prevention strategies for the benefit of crew health, both during and after long-duration space exploration, and mission success.

The proposed research will take advantage of an established population-based cohort, which includes men and women of an age range similar to crewmembers in the US space program, who have had bone density measured over time. We will make comparisons between bone densities of crewmembers and the population-based data and use fracture prediction models derived from the cohort to make estimations on fracture risk among crewmembers. We will also explore the data already gathered to date during the US human space program in order to summarize the current state of evidence available on additional risk factors related to bone loss and recovery in microgravity. The ultimate goal of this research proposal is to provide evidence-based information which may assist in guiding the direction of further research required to better understand the risk of bone loss and fracture among crewmembers and the strategies that could be developed to prevent it from occurring.

Research Impact/Earth Benefits: This work will help establish the occupational risk of short and long-duration microgravity exposure on longterm bone health consequences among U.S. crewmembers. It will also serve to provide a comprehensive summary of the current evidence available on risk factors related to bone loss and recovery among U.S. crewmembers following long-duration space flight.

Task Progress & Bibliography Information FY2011 
Task Progress: Overview of Year 3

As investigators external to NASA, we have encountered several different data access issues which have posed a challenge to progress on work over the years. We continue to work with our collaborators at NASA to identify ways to overcome these challenges in order to make progress on analyses. During this third year of funding, NASA-JSC colleagues have completed assembly of the bone density datasets for U.S. crewmembers who have consented to the study. At NASA-JSC, comprehensive risk factors known to be related to bone health are being assembled and work is ongoing. At Mayo, data analyses for Aim 1 have progressed on bone density changes in both short and long-duration crewmembers. Fracture prediction models have been developed using the Mayo cohort. Data cleaning and exploratory work for Aim 2 is ongoing based on risk factor data available, but some data is still being assembled.

Progress Related to AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk.

Informed consent has now been achieved in all 36 U.S. crewmembers (28 men, 8 women) who have flown on at least one long-duration space mission on Mir or ISS and had a postflight bone density measured as of December 2010 (100% participation rate). We have also obtained informed consent on U.S. crewmembers (26 women and 158 men) who have flown on a short-duration mission and had at least one bone density measurement available as of December 2010 (85% participation rate).

We created age- and gender-expected prediction models for bone mineral density (BMD) derived from 348 men (age range at baseline: 22-90 years) and 351 women (range: 21-93 years) representing an age-stratified, random sample of the adult community population (Mayo Rochester Bone Health Study cohort) and who have had longitudinal BMD measurements at identical sites to the U.S. crewmembers. We have applied the created prediction models to the NASA cohort of long-duration U.S. crewmembers.

Based on our prediction models, following 6-18 months after returning from a long-duration flight, BMD at most sites was still lower than predicted in men. However, in women BMD at all sites was not significantly different than what would be predicted. In additional analyses in men extending follow-up to 3 years after return from a long-duration flight, BMD at most sites was now closer to predicted except for the hip where it was still significantly lower than predicted. Preliminary results have been presented within this past year at national meetings of the American Society of Bone and Mineral Research, American College of Rheumatology, and the International Academy of Astronautics.

In analyses involving U.S. crew who have only served on short-duration missions in space, we found that men who had longer cumulative days in space had lower bone density at the spine but not other sites. In women, we found no significant association between BMD, at any site, and duration of space exposure. These initial results therefore suggest that there may not be any long-term negative effects of short duration spaceflight on bone density in women or, at most sites, in men. Our preliminary findings were presented at the annual meeting of the Aerospace Medical Association.

Progress Related to AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.

Data assembly at NASA-JSC on risk factors known to be related to bone loss and fracture risk is ongoing. We will use these data to help better understand the variability in BMD loss and recovery, post-flight. Risk factor data include, but are not limited to, medication use, bone turnover markers, and surrogates of exercise status in-flight, such as changes in strength measures, and lean muscle mass. Data assembly and cleaning is ongoing. Exploratory descriptive analyses are being conducted on data available.

Bibliography Type: Description: (Last Updated: 07/01/2019)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Amin S, Achenbach SJ, Atkinson EJ, Melton LJ, Khosla S, Sibonga J. "Bone Density Following Long-Duration Spaceflight and Recovery." Presented at the 2010 American Society of Bone and Mineral Research Annual Meeting; Toronto, Ontario, Canada, October 15-19,2010.

J Bone Miner Res 2010 Sep;25(Suppl 1):SA0319. Available at: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=d5b1d514-89d3-44a4-add2-44aadefbfd3a ; accessed 6/02/2011. , Sep-2010

Abstracts for Journals and Proceedings Amin S, Achenbach SJ, Atkinson EJ, Melton LJ, Khosla S, Sibonga J. "Bone Density Following Long-Duration Spaceflight and Recovery." Presented at the 74th Annual Scientific Meeting of the American College of Rheumatology, Atlanta, Georgia, November 6-11, 2010.

Arthritis & Rheumatism 2010 Oct;62(10 Suppl):S398 (abstract #959). http://www.rheumatology.org/education/annual/FinalAbstract2010.pdf , Oct-2010

Abstracts for Journals and Proceedings Amin S, Achenbach SJ, Atkinson EJ, Sibonga JD. "Bone Density Following Three Years of Recovery from Long-Duration Space Flight." Presented at the 18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011.

18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011. , Apr-2011

Abstracts for Journals and Proceedings Amin S, Achenbach SJ, Atkinson EJ, Khosla S, Sibonga JD. "Does Short-Duration Space Flight Have a Negative Effect on Bone Density?" Presented at the 82nd Annual Scientific Meeting of the Aerospace Medical Association, Anchorage, Alaska, May 8-12, 2011.

Aviation, Space, and Environmental Medicine. 2011 Mar;82(3):266 (abstract #189). , Mar-2011

Significant Media Coverage Amin S, Achenbach SJ, Atkinson EJ, Melton LJ, Khosla S, Sibonga J. "Press release on abstract, 'Bone Density Following Long-Duration Spaceflight and Recovery,' presented at the 74th Annual Scientific Meeting of the American College of Rheumatology." Press release, 74th Annual Scientific Meeting of the American College of Rheumatology, November 2011., Nov-2011
Project Title:  Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long Duration Space Flight Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/01/2008  
End Date: 07/31/2012  
Task Last Updated: 06/03/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Amin, Shreyasee  M.D. / Mayo Clinic College of Medicine 
Address:  200 First Street SW 
 
Rochester , MN 55905 
Email: amin.shreyasee@mayo.edu 
Phone: 507-284-4277  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mayo Clinic College of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Khosla, Sundeep  Mayo Clinic 
Sibonga, Jean  USRA 
Key Personnel Changes / Previous PI: None in past year.
Project Information: Grant/Contract No. NNX08AQ20G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NNX08AQ20G 
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) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Osteo04:We do not 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 (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date changed to 7/31/2012 per C. Guidry/JSC (2/7/2011)

NOTE: Period of performance changed to 8/1/2008-7/31/2011 (from 5/20/08-5/19/11) per C. Guidry/JSC (3/2010)

Task Description: Bone loss is estimated to occur at a rate of 1% per month in space (microgravity), particularly in weight-bearing bones in the legs and spine. This rate of loss is equivalent to what we might lose in a year with advancing age on Earth. It remains unknown what this loss signifies for future fracture risk in crewmembers. While unloading of the skeleton in the weightless environment of space is considered the key factor contributing to bone loss, there are likely other factors that also play a role. Current prevention strategies have not been effective at preventing this bone loss. Improved understanding on the risk for fracture following long-duration space flight, as well as the factors contributing to bone loss in microgravity, and its recovery, are needed in order to develop better prevention strategies for the benefit of crew health, both during and after long-duration space exploration, and mission success. The proposed research will take advantage of an established population-based cohort, which includes men and women of an age range similar to crewmembers in the US space program, who have had bone density measured over time. We will make comparisons between bone densities of crewmembers and the population-based data and use fracture prediction models derived from the cohort to make estimations on fracture risk among crewmembers. We will also explore the data already gathered to date during the US human space program in order to summarize the current state of evidence available on additional risk factors related to bone loss and recovery in microgravity. The ultimate goal of this research proposal is to provide evidence-based information which may assist in guiding the direction of further research required to better understand the risk of bone loss and fracture among crewmembers and the strategies that could be developed to prevent it from occurring.

Research Impact/Earth Benefits: This work will help establish the occupational risk of short and long-duration microgravity exposure on longterm bone health consequences among US crewmembers. It will also serve to provide a comprehensive summary of the current evidence available on risk factors related to bone loss and recovery among US crew members following long-duration space flight.

Task Progress & Bibliography Information FY2010 
Task Progress: I. SPECIFIC AIMS:

AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk.

AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.

II. SUMMARY OF WORK RELATED TO AIMS:

A. Overview of Year 2

During this second year of funding, NASA-JSC colleagues have been assembling the bone density datasets for all remaining US crewmembers and consenting the approximate 250 men and women in the US space program, who have had at least one bone density measured. At NASA-JSC, comprehensive risk factors known to be related to bone health are also being assembled and work is ongoing. At Mayo, data analyses for Aim 1 have been initiated with respect to the bone density data available on long-duration crewmembers. Fracture prediction models have also been developed using data on risk factors available in both US long-duration crewmembers and in the Mayo cohort. Initial data cleaning and exploratory work for Aim 2 has begun based on risk factor data available and shared to date, although complete datasets on risk factors (e.g., ,bone turnover markers, lean muscle mass, personal and family history of fractures, medication use, etc) are still being assembled.

B. Progress Related to AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk. .

Informed consent has been achieved in all 32 US crewmembers (26 men, 7 women; age range: 37-54 years) who have flown on at least one long-duration space mission (100% participation rate).

To date, we have obtained informed consent on 123 (53%) of the 232 remaining US crewmembers (21/36 women and 102/196 men) who have had at least one bone density measurement available. The consenting process is ongoing. 3 have declined and 3 are lost to follow-up.

Bone density datasets for all long-duration crewmembers have been assembled and cleaned. Bone density datasets for the remaining US crewmembers are still being assembled at NASA-JSC. We anticipate that NASA-JSC colleagues will have consenting status complete and bone density datasets assembled and ready to share with Mayo investigators, for those who have consented, by the end of the second year of funding.

i) Creation of a bone mineral density (BMD) prediction model using the Mayo cohort:

We have created age- and gender-expected prediction models for BMD derived from 348 men (age range at baseline: 22-90 years) and 351 women (range: 21-93 years) representing an age-stratified, random sample of the adult community population (Mayo Rochester Bone Health Study cohort) and who have had longitudinal BMD measurements at identical sites to the US crewmembers. We then applied the created prediction models to the NASA cohort of long-duration US crewmembers.

Based on our models, the BMD at all sites immediately post-flight in US crewmembers were all significantly lower than would be expected. We did observe a unique finding of greater than expected loss of BMD in some upper arm sites which raises the possibility of other risk factors contributing to bone loss during space flight unrelated to mechanical unloading, but is being further explored. There were also observed differences between men and women which warrant further exploration, and that will be addressed in analyses related to Aim 2.

Preliminary work also reveal that following 6-18 months post-flight, BMD at most sites in US long-duration crewmembers is becoming closer to the expected values. However, the hip BMD still is significantly lower than expected at 1 year post-flight.

ii) Creation of a fracture prediction model using the Mayo cohort:

Fracture prediction models were also created using the Mayo Rochester Bone Health Study cohort, separately for men and women who were at least age 35. Fracture predictions for 5 and 10 years following the BMD measurement were estimated for immediate pre-flight, immediate post-flight and ~1 year post-flight BMD. We are currently conducting further analyses towards improvement of these models before final interpretation.

C. Progress Related to AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.

Data assembly at NASA-JSC on risk factors known to be related to bone loss and fracture risk is ongoing. We will use these data to help better understand the variability in BMD loss and recovery, post-flight. Risk factor data include, but are not limited to, medication use, personal and family history of fractures, bone turnover markers, and surrogates of exercise status in-flight, such as changes in strength measures, VO2 max and lean muscle mass. Data assembly and cleaning is ongoing. Exploratory descriptive analyses are being conducted on data available. Observed differences between men and women in Aim 1 will also be explored further by examining the role of different risk factors on bone loss.

Bibliography Type: Description: (Last Updated: 07/01/2019)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Amin S. "Mechanical factors and bone health: Effects of weightlessness and neurologic injury." Current Rheumatology Reports. 2010 Jun;12(3):170-6. Review. PMID: 20425519 , Jun-2010
Project Title:  Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long Duration Space Flight Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/01/2008  
End Date: 07/31/2011  
Task Last Updated: 07/31/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Amin, Shreyasee  M.D. / Mayo Clinic College of Medicine 
Address:  200 First Street SW 
 
Rochester , MN 55905 
Email: amin.shreyasee@mayo.edu 
Phone: 507-284-4277  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mayo Clinic College of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Khosla, Sundeep  Mayo Clinic 
Sibonga, Jean  USRA 
Key Personnel Changes / Previous PI: The Ph D statistician on this project at JSC was changed from Dr. Matthew Hayat, who left USRA, to Dr. Robert Ploutz-Snyder, who is his replacement at USRA.
Project Information: Grant/Contract No. NNX08AQ20G 
Responsible Center: NASA JSC 
Grant Monitor: Meck, J@n  
Center Contact: 281-244-5405 
janice.v.meck@nasa.gov 
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NNX08AQ20G 
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) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Osteo04:We do not 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 (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Period of performance changed to 8/1/2008-7/31/2011 (from 5/20/08-5/19/11) per C. Guidry/JSC (3/2010)

Task Description: Bone loss is estimated to occur at a rate of 1% per month in space (microgravity), particularly in weight-bearing bones in the legs and spine. This rate of loss is equivalent to what we might lose in a year with advancing age on Earth. It remains unknown what this loss signifies for future fracture risk in crewmembers. While unloading of the skeleton in the weightless environment of space is considered the key factor contributing to bone loss, there are likely other factors that also play a role. Current prevention strategies have not been effective at preventing this bone loss. Improved understanding on the risk for fracture following long-duration space flight, as well as the factors contributing to bone loss in microgravity, and its recovery, are needed in order to develop better prevention strategies for the benefit of crew health, both during and after long-duration space exploration, and mission success. The proposed research will take advantage of an established population-based cohort, which includes men and women of an age range similar to crewmembers in the US space program, who have had bone density measured over time. We will make comparisons between bone densities of crewmembers and the population-based data and use fracture prediction models derived from the cohort to make estimations on fracture risk among crewmembers. We will also explore the data already gathered to date during the US human space program in order to summarize the current state of evidence available on additional risk factors related to bone loss and recovery in microgravity. The ultimate goal of this research proposal is to provide evidence-based information which may assist in guiding the direction of further research required to better understand the risk of bone loss and fracture among crewmembers and the strategies that could be developed to prevent it from occurring.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2009 
Task Progress: I. SPECIFIC AIMS:

AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk.

AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.

II. SUMMARY OF WORK TO DATE RELATED TO AIMS:

During this first year of funding we have been assembling the data required for the proposed analyses. Work at both Mayo Clinic and Johnson Space Center-NASA (JSC-NASA) is ongoing to complete the goals of these aims.

At Mayo Clinic, we have updated the fracture incidence data from our population-based cohort of men and women from the Rochester Bone Health Study. This data will be used for the fracture prediction models in Aim 1. Fracture incidence is now complete for our cohort through to the end of 2008.

At JSC-NASA, work is ongoing to assemble data and coordinate the logistics for analyses to be performed by Mayo Clinic statisticians. We have achieved 100% participation from eligible long-duration crew members, have assembled some of the key data for analyses and have made major strides in achieving secure remote access to the JSC-NASA servers, which the Mayo Clinic investigators need in order to begin analyses of the data.

Our progress during the first year has been slower than anticipated. As investigators outside NASA requesting access to previously collected archived clinical data from crew members, we are working through many uncharted issues related to our access of the data for our analyses. Most have been overcome, but the logistics of obtaining security clearance and remote access for Mayo Clinic investigators were complex and lengthy. As of the end of May 2009, the final steps in obtaining remote access to the secure servers at JSC-NASA were still being finalized and data analyses are expected to start by the summer of 2009.

Our initial timeline was to complete Aim 1 over the first 1.5 years of funding. Although our progress has been slower than anticipated, given the unprecedented nature of this work and some of our unique requirements, we have, in fact, made considerable progress towards the goals of this proposal. There will be undoubtedly additional logistic or uncharted issues to address surrounding our analyses as we proceed, but we will continue to work with our collaborators at JSC-NASA towards completing most of the sub-aims in Aim 1 by the middle of the second year of funding. We have been fortunate to be working with a committed team of collaborators at JSC-NASA who have been a considerable asset in assisting us with this work. Our goal is to start Aim 2 towards the latter half of the second year of funding.

Bibliography Type: Description: (Last Updated: 07/01/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2009
Project Title:  Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long Duration Space Flight Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 05/20/2008  
End Date: 05/19/2011  
Task Last Updated: 06/26/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Amin, Shreyasee  M.D. / Mayo Clinic College of Medicine 
Address:  200 First Street SW 
 
Rochester , MN 55905 
Email: amin.shreyasee@mayo.edu 
Phone: 507-284-4277  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mayo Clinic College of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Khosla, Sundeep  Mayo Clinic 
Sibonga, Jean  USRA 
Project Information: Grant/Contract No. NNX08AQ20G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NNX08AQ20G 
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) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) Osteo04:We do not 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 (IRP Rev E)
Task Description: Bone loss is estimated to occur at a rate of 1% per month in space (microgravity), particularly in weight-bearing bones in the legs and spine. This rate of loss is equivalent to what we might lose in a year with advancing age on Earth. It remains unknown what this loss signifies for future fracture risk in crewmembers. While unloading of the skeleton in the weightless environment of space is considered the key factor contributing to bone loss, there are likely other factors that also play a role. Current prevention strategies have not been effective at preventing this bone loss. Improved understanding on the risk for fracture following long-duration space flight, as well as the factors contributing to bone loss in microgravity, and its recovery, are needed in order to develop better prevention strategies for the benefit of crew health, both during and after long-duration space exploration, and mission success. The proposed research will take advantage of an established population-based cohort, which includes men and women of an age range similar to crewmembers in the US space program, who have had bone density measured over time. We will make comparisons between bone densities of crewmembers and the population-based data and use fracture prediction models derived from the cohort to make estimations on fracture risk among crewmembers. We will also explore the data already gathered to date during the US human space program in order to summarize the current state of evidence available on additional risk factors related to bone loss and recovery in microgravity. The ultimate goal of this research proposal is to provide evidence-based information which may assist in guiding the direction of further research required to better understand the risk of bone loss and fracture among crewmembers and the strategies that could be developed to prevent it from occurring.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2008 
Task Progress: New project for FY2008.

Bibliography Type: Description: (Last Updated: 07/01/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2008