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Project Title:  Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021 Reduce
Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 03/31/2017  
Task Last Updated: 08/24/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   LeBlanc, Adrian  Ph.D. / Universities Space Research Association 
Address:  Division of Space Life Sciences  
3600 Bay Area Blvd 
Houston , TX 77058 
Email: adleblanc2@gmail.com 
Phone: 281-244-2012  
Congressional District: 22 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Universities Space Research Association 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jones, Jeffrey  M.D. Baylor College of Medicine 
Shapiro, Jay  M.D. Kennedy Krieger Institute 
Lang, Tom  Ph.D. University of California at San Francisco 
Shackelford, Linda  M.D. NASA Johnson Space Center 
Smith, Scott  Ph.D. NASA-Johnson Space Center 
Evans, Harlan  Ph.D. Wyle Laboratories 
Spector, Elisabeth  Wyle Laboratories 
Sibonga, Jean  Ph.D. NASA Johnson Space Center 
Nakamura, Toshitaka  M.D., Ph.D. University of Occupational and Environmental Health 
Kohri, Kenjiro  M.D., Ph.D. Nagoya City University 
Ohshima, Hiroshi  M.D., Ph.D. Japan Aerospace Exploration Agency (JAXA) 
Keyak, Joyce  Ph.D. University of California, Irvine 
Yasui, Takahura  M.D., Ph.D. Nagoya City University 
Okada, Atsushi  M.D., Ph.D. Nagoya City University 
Matsumoto, Toshio  M.D., Ph.D. Co-PI : University of Tokushima Graduate School of Medicine, Japan 
Key Personnel Changes / Previous PI: August 2016 Report: Drs. Takahura Yasui, M.D., Ph.D. and Atsushi Okada, M.D., Ph.D. (both from Nagoya City University) have been added as Co-Investigators to provide expertise in the analysis and interpretation of renal stone-related data. August 2013 Report: Dr. Joyce Keyak (University of California at Irvine) has been added as a Co-Investigator. Dr. Keyak provides expertise in the area of Finite Element Modeling using hip QCT scans, and she is a co-author of presentations and publications resulting from this flight study. Toshio Matsumoto, M.D., Ph.D., is the Japanese Co-Principal Investigator of this study, a joint project between NASA and JAXA. Dr. Matsumoto is affiliated with the Department of Medicine and Regulatory Sciences, University of Tokushima Graduate School of Medicine. His contact information is: Phone 81-88-633-7119/Fax 81-88-633-7407; Toshimat@clin.med.tokkushima-u.ac.jp .
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Maher, Jacilyn  
Center Contact:  
jacilyn.maher56@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: Yes 
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) Osteo07:We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight (IRP Rev E)
Flight Assignment/Project Notes: ISS

NOTE: End date changed to 3/31/2017 due to PI's retirement (Ed., 8/2/17)

NOTE: End date changed to 2/03/2018 per HRP technology information (Ed., 9/2/14)

NOTE: End date is 8/31/2015 per HRP Master Task List dtd 7/12/11 (Ed., 8/4/11)

NOTE: Extended to 9/30/2013 per PI (Ed., 11/5/2010)

Task Description: The purpose of this Supplementary Medical Objective is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect International Space Station (ISS) crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens will be tested: (1) an oral dose of 70 mg alendronate taken weekly during flight and (2) and I.V. dose of zoledronic acid 4 mg, administered just once approximately 45 days before flight. Our rationale for including both alendronate and zoledronic acid is that two dosing options will: maximize crew participation, increase the countermeasure options available to flight surgeons, increase scientific opportunities, and minimize the effects of operational and logistical constraints. Use of both oral and I.V. options can accommodate both crew and flight surgeon preferences (e.g., based on individual drug sensitivity, relevant health conditions, or other considerations). Operational and logistical constraints may favor one option versus the other. For example, stowage limits may limit use of alendronate on certain flights, while the ability to titrate the in-flight dose in response to on-orbit measurements of bone resorption would favor the weekly dosing regimen. Long-duration (e.g., 2+ year) missions would require in-flight re-dosing of I.V. zoledronic acid. The purpose of this study is not to test one dosing option versus the other. Rather, we intend to show that bisphosphonates-plus-exercise will have a measurable effect versus exercise alone in preventing space flight induced bone loss. Secondary goals will be to document the return to normal bone remodeling post-flight in crewmembers who took bisphosphonates.

See also https://www.nasa.gov/mission_pages/station/research/experiments/explorer/Investigation.html?#id=232

Research Impact/Earth Benefits: While the primary purpose of this research is to develop a countermeasure to protect crewmembers against bone loss during long duration space flight, this research may provide insight into the mechanisms and prevention of bone atrophy in other disuse conditions.

Task Progress & Bibliography Information FY2017 
Task Progress: The original intent of this study was to test 10 long-duration crewmembers taking one of two bisphosphonate regimens: either 70 mg per week alendronate or a single infusion of 4 mg of Zoledronic acid. After the study began testing in 2009, the Johnson Space Center (JSC) Committee for the Protection of Human Subjects (CPHS) determined that only alendronate would be offered to U.S. crewmembers, while both dosing options could be offered to International Partners. It was further stipulated that only 10 alendronate subjects would be allowed. Of these, 2 dropped out prior to flight for various reasons and one crewmember reported GI symptoms very early inflight and therefore the investigators terminated the inflight dosing of this subject. We have now completed testing on the remainder 7 crewmembers taking alendronate during flight.

All scheduled testing sessions for the 7 treated subjects—pre-flight, in-flight and post-flight--have been completed. DXA, pQCT, QCT, and blood and urine data have been collated and analyses of the major parameters of interest have been performed through R+30, including statistical analyses. These results were published in June 2013 in the journal Osteoporosis International (LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith SM, Evans H, Spector E, Ploutz-Snyder R, et al. (2013). Bisphosphonates as a supplement to exercise to protect bone during long-duration space flight. Osteoporosis International 24(7): 2105-2114). The results of R+12-month testing (DXA and QCT) on this group were presented at the 2014 Meeting of the American Society for Bone and Mineral Research in Houston, TX, (September 2014) and at the NASA Human Research Program Investigators’ Workshop in Galveston, TX, (February 2015). Additional updates were presented at the 2016 NASA Human Research Program Investigator’s Workshop in Galveston, TX, (February 2016) and the 2017 NASA Human Research Program Investigator’s Workshop in Galveston, TX, in January 2017.

In 2011, the study obtained approval to add a new control group, consisting of approximately 10 ISS crewmembers not taking bisphosphonates, but otherwise participating in essentially the same pre-, in-, and post-flight testing as the 7 treated subjects. The new control group should allow us to distinguish the relative effects of bisphosphonates vs. the confounder of Advanced Resistive Exercise Device (ARED) exercise, particularly at the level of trabecular vs. cortical bone. All treated subjects in this study have used the ARED device, whereas our previous control group used the older IRED or other resistive exercise device, capable of much lower loads than ARED. Testing on this new control group began in 2012, and, to date, 10 crewmembers have consented to participate. Of these, 9 crewmembers have returned from ISS flights. Eight of these have completed all post-flight testing through R+1 year, one has completed all post flight testing except one year return, and the remaining test subject has completed preflight testing.

Immediate post-flight testing on this subject is expected in late 2016. It is anticipated that the control group will complete testing in ~late 2017. Preliminary results (DXA and QCT) for the first 9 of these control subjects will be presented at the 2016 Meeting of the American Society for Bone and Mineral Research in Atlanta GA, (September 2016).

All testing to date for the first 8 control subjects, including QCT, DXA, pQCT, abdominal ultrasound, and blood and urine testing, has been completed on schedule and without incident. ISS sample return is complete for the first 6 control subjects.

In Summary (as of March 2017)

Exercise + Alendronate

7 crewmembers completed ISS mission (mean 5.5mo). All crewmembers took 70mg/wk oral alendronate starting 3 weeks prior to and during flight.

Results are: reduced bone loss, eliminated elevated resorption and uncoupling, reduced urinary Ca and calculated bone strength was maintained. Results published in 2013

ARED exercise alone

Ten subjects completed flight using newer exercise protocol and device (ARED)

Results-reduced bone loss by about 50% compared to early ISS crewmembers using IRED, systemic resorption remains elevated, uncoupling appears to remain elevated for most of flight based on systemic markers, urinary Ca remains elevated and bone strength appears to be maintained

Bibliography Type: Description: (Last Updated: 10/15/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford LC, Smith SM, Evans HJ, Spector ER, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H, Moralez G. "Update of Bisphosphonate Flight Experiment." Presented at the 2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015.

2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015. , Jan-2015

Abstracts for Journals and Proceedings LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford LC, Smith SM, Evans HJ, Spector ER, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H, Moralez G. "Spaceflight Bone Atrophy: Problem Solved? " 37th Annual Meeting of the American Society for Bone and Mineral Research, Seattle, Washington, October 9-12, 2015.

Journal of Bone and Mineral Research. 2015;30 (Suppl 1). , Oct-2015

Abstracts for Journals and Proceedings LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford LC, Smith SM, Evans HJ, Spector ER, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H, Moralez G. "Update of Bisphosphonate Flight Experiment." 2016 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 8-11, 2016.

2016 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 8-11, 2016. , Feb-2016

Abstracts for Journals and Proceedings Spector ER, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford LC, Smith SM, Evans HJ, Spector ER, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H, Moralez G, LeBlanc A. "Bone Loss Countermeasures for Long Duration Space Flight." ASBMR 2016 (American Society for Bone and Mineral Research), Atlanta, Georgia, September 16-19, 2016.

ASBMR 2016 (American Society for Bone and Mineral Research), Atlanta, Georgia, September 16-19, 2016. , Sep-2016

Abstracts for Journals and Proceedings LeBlanc A. "Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-21." 2017 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 23-26, 2017.

2017 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 23-26, 2017. , Jan-2017

Articles in Peer-reviewed Journals Sibonga J, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith SM, Young M, Keyak J, Kohri K, Ohshima H, Spector E, LeBlanc A. "Resistive exercise in astronauts on prolonged spaceflights provides partial protection against spaceflight-induced bone loss." Bone. 2019 Nov;128:112037. [2019 Aug 7 Epub] https://doi.org/10.1016/j.bone.2019.07.013 ; PubMed PMID: 31400472 , Nov-2019
Books/Book Chapters Schneider VS, Ploutz-Snyder L, LeBlanc AD, Sibonga J. "Musculoskeletal adaptation to space flight." in "Space physiology and medicine: From evidence to practice. " Ed. A.E. Nicogossian et al. New York: Springer, 2016. p. 347-365. https://doi.org/10.1007/978-1-4939-6652-3_13 , Dec-2016
Project Title:  Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021 Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 03/31/2017  
Task Last Updated: 08/27/2015 
Download report in PDF pdf
Principal Investigator/Affiliation:   LeBlanc, Adrian  Ph.D. / Universities Space Research Association 
Address:  Division of Space Life Sciences  
3600 Bay Area Blvd 
Houston , TX 77058 
Email: adleblanc2@gmail.com 
Phone: 281-244-2012  
Congressional District: 22 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Universities Space Research Association 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jones, Jeffrey  Baylor College of Medicine 
Shapiro, Jay  M.D. Kennedy Krieger Institute 
Lang, Tom  Ph.D. University of California at San Francisco 
Shackelford, Linda  M.D. NASA Johnson Space Center 
Smith, Scott  Ph.D. NASA-Johnson Space Center 
Evans, Harlan  Ph.D. Wyle Laboratories 
Spector, Elisabeth  Wyle Laboratories 
Sibonga, Jean  Ph.D. Universities Space Research Association (USRA) 
Nakamura, Toshitaka  M.D., Ph.D. University of Occupational and Environmental Health 
Kohri, Kenjiro  M.D., Ph.D. Nagoya City University 
Ohshima, Hiroshi  M.D., Ph.D. Japan Aerospace Exploration Agency (JAXA) 
Keyak, Joyce  University of California, Irvine 
Key Personnel Changes / Previous PI: August 2013 Report: Dr. Joyce Keyak (University of California at Irvine) has been added as a Co-Investigator. Dr. Keyak provides expertise in the area of Finite Element Modeling using hip QCT scans, and she is a co-author of presentations and publications resulting from this flight study. Toshio Matsumoto, M.D., Ph.D., is the Japanese Co-Principal Investigator of this study, a joint project between NASA and JAXA. Dr. Matsumoto is affiliated with the Department of Medicine and Regulatory Sciences, University of Tokushima Graduate School of Medicine. His contact information is: Phone 81-88-633-7119/Fax 81-88-633-7407; Toshimat@clin.med.tokkushima-u.ac.jp .
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Maher, Jacilyn  
Center Contact:  
jacilyn.maher56@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: Yes 
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) Osteo07:We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight (IRP Rev E)
Flight Assignment/Project Notes: ISS

NOTE: End date changed to 3/31/2017 due to PI's retirement (Ed., 8/2/17)

NOTE: End date changed to 2/03/2018 per HRP technology information (Ed., 9/2/14)

NOTE: End date is 8/31/2015 per HRP Master Task List dtd 7/12/11 (Ed., 8/4/11)

NOTE: Extended to 9/30/2013 per PI (Ed., 11/5/2010)

Task Description: The purpose of this Supplementary Medical Objective is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect International Space Station (ISS) crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens will be tested: (1) an oral dose of 70 mg alendronate taken weekly during flight and (2) and I.V. dose of zoledronic acid 4 mg, administered just once approximately 45 days before flight. Our rationale for including both alendronate and zoledronic acid is that two dosing options will: maximize crew participation, increase the countermeasure options available to flight surgeons, increase scientific opportunities, and minimize the effects of operational and logistical constraints. Use of both oral and I.V. options can accommodate both crew and flight surgeon preferences (e.g., based on individual drug sensitivity, relevant health conditions, or other considerations). Operational and logistical constraints may favor one option versus the other. For example, stowage limits may limit use of alendronate on certain flights, while the ability to titrate the in-flight dose in response to on-orbit measurements of bone resorption would favor the weekly dosing regimen. Long-duration (e.g., 2+ year) missions would require in-flight re-dosing of I.V. zoledronic acid. The purpose of this study is not to test one dosing option versus the other. Rather, we intend to show that bisphosphonates-plus-exercise will have a measurable effect versus exercise alone in preventing space flight induced bone loss. Secondary goals will be to document the return to normal bone remodeling post-flight in crewmembers who took bisphosphonates.

Research Impact/Earth Benefits: While the primary purpose of this research is to develop a countermeasure to protect crewmembers against bone loss during long duration space flight, this research may provide insight into the mechanisms and prevention of bone atrophy in other disuse conditions.

Task Progress & Bibliography Information FY2016 
Task Progress: The original intent of this study was to test 10 long-duration crewmembers taking one of two bisphosphonate regimens: either 70 mg per week alendronate or a single infusion of 4 mg of zoledronic acid. After the study began testing in 2009, the Johnson Space Center (JSC) Committee for the Protection of Human Subjects (CPHS) determined that only alendronate would be offered to U.S. crewmembers, while both dosing options could be offered to International Partners. It was further stipulated that only 7 alendronate subjects would be allowed. We have now completed testing on all 7 of these alendronate subjects. No further subjects will be tested with bisphosphonates.

All scheduled testing sessions for the 7 treated subjects—pre-flight, in-flight, and post-flight--have been completed. Dual-energy X-ray absorptiometry (DXA), pQCT (peripheral QCT), quantitative computed tomography (QCT), and blood and urine data have been collated and analyses of the major parameters of interest have been performed through R+30, including statistical analyses. These results were published in June 2013 in the journal Osteoporosis International (LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith SM, Evans H, Spector E, Ploutz-Snyder R, et al. (2013). Bisphosphonates as a supplement to exercise to protect bone during long-duration space flight. Osteoporosis International 24(7): 2105-2114). Preliminary results of R+12-month testing (DXA and QCT) on this group were presented at the 2014 Meeting of the American Society for Bone and Mineral Research in Houston, TX, (September 2014) and at the NASA Human Research Program Investigators’ Workshop in Galveston, TX, (February 2015).

In 2011, the study obtained approval to add a new control group, consisting of approximately 10 International Space Station (ISS) crewmembers not taking bisphosphonates, but otherwise participating in essentially the same pre-, in-, and post-flight testing as the 7 treated subjects. The new control group should allow us to distinguish the relative effects of bisphosphonates vs. the confounder of Advanced Resistive Exercise Device (ARED) exercise, particularly at the level of trabecular vs. cortical bone. (All treated subjects in this study have used the ARED device, whereas our previous control group used the older IRED or other resistive exercise device, capable of much lower loads than ARED.) Testing on this new control group began in 2012, and, to date, 9 crewmembers have consented to participate. Of these, 8 crewmembers have returned from ISS flights. Five of these have completed all post-flight testing through R+1 year and the remaining 3 have completed post-flight testing through R+30 days. One additional subject will return from ISS in December 2015. Informed consent briefings continue in an effort to recruit a 10th control subject. It is anticipated that the control group will complete testing in ~late 2017. Preliminary results (DXA and QCT) for the first 5 of these control subjects were presented at the 2014 Meeting of the American Society for Bone and Mineral Research in Houston, TX, (September 2014).

All testing to date for the first 8 control subjects, including QCT, DXA, pQCT, abdominal ultrasound, and blood and urine testing, has been completed on schedule and without incident. ISS sample return is complete for the first 5 control subjects.

Bibliography Type: Description: (Last Updated: 10/15/2019) 

Show Cumulative Bibliography Listing
 
 None in FY 2016
Project Title:  Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021 Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 08/31/2015  
Task Last Updated: 08/21/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   LeBlanc, Adrian  Ph.D. / Universities Space Research Association 
Address:  Division of Space Life Sciences  
3600 Bay Area Blvd 
Houston , TX 77058 
Email: adleblanc2@gmail.com 
Phone: 281-244-2012  
Congressional District: 22 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Universities Space Research Association 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jones, Jeffrey  Baylor College of Medicine 
Shapiro, Jay  M.D. Kennedy Krieger Institute 
Lang, Tom  Ph.D. University of California at San Francisco 
Shackelford, Linda  M.D. NASA Johnson Space Center 
Smith, Scott  Ph.D. NASA-Johnson Space Center 
Evans, Harlan  Ph.D. Wyle Laboratories 
Spector, Elisabeth  Wyle Laboratories 
Sibonga, Jean  Ph.D. Universities Space Research Association (USRA) 
Nakamura, Toshitaka  M.D., Ph.D. University of Occupational and Environmental Health 
Kohri, Kenjiro  M.D., Ph.D. Nagoya City University 
Ohshima, Hiroshi  M.D., Ph.D. Japan Aerospace Exploration Agency (JAXA) 
Keyak, Joyce  University of California, Irvine 
Key Personnel Changes / Previous PI: August 2013 Report: Dr. Joyce Keyak (University of California at Irvine) has been added as a Co-Investigator. Dr. Keyak provides expertise in the area of Finite Element Modeling using hip QCT scans, and she is a co-author of presentations and publications resulting from this flight study. Toshio Matsumoto, M.D., Ph.D., is the Japanese Co-Principal Investigator of this study, a joint project between NASA and JAXA. Dr. Matsumoto is affiliated with the Department of Medicine and Regulatory Sciences, University of Tokushima Graduate School of Medicine. His contact information is: Phone 81-88-633-7119/Fax 81-88-633-7407; Toshimat@clin.med.tokkushima-u.ac.jp .
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Maher, Jacilyn  
Center Contact:  
jacilyn.maher56@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: Yes 
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) Osteo07:We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight (IRP Rev E)
Flight Assignment/Project Notes: ISS

NOTE: End date is 8/31/2015 per HRP Master Task List dtd 7/12/11 (Ed., 8/4/11)

NOTE: Extended to 9/30/2013 per PI (Ed., 11/5/2010)

Task Description: The purpose of this Supplementary Medical Objective is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect International Space Station (ISS) crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens will be tested: (1) an oral dose of 70 mg alendronate taken weekly during flight and (2) and I.V. dose of zoledronic acid 4 mg, administered just once approximately 45 days before flight. Our rationale for including both alendronate and zoledronic acid is that two dosing options will: maximize crew participation, increase the countermeasure options available to flight surgeons, increase scientific opportunities, and minimize the effects of operational and logistical constraints. Use of both oral and I.V. options can accommodate both crew and flight surgeon preferences (e.g., based on individual drug sensitivity, relevant health conditions, or other considerations). Operational and logistical constraints may favor one option versus the other. For example, stowage limits may limit use of alendronate on certain flights, while the ability to titrate the in-flight dose in response to on-orbit measurements of bone resorption would favor the weekly dosing regimen. Long-duration (e.g., 2+ year) missions would require in-flight re-dosing of I.V. zoledronic acid. The purpose of this study is not to test one dosing option versus the other. Rather, we intend to show that bisphosphonates-plus-exercise will have a measurable effect versus exercise alone in preventing space flight induced bone loss. Secondary goals will be to document the return to normal bone remodeling post-flight in crewmembers who took bisphosphonates.

Research Impact/Earth Benefits: While the primary purpose of this research is to develop a countermeasure to protect crewmembers against bone loss during long duration space flight, this research may provide insight into the mechanisms and prevention of bone atrophy in other disuse conditions.

Task Progress & Bibliography Information FY2015 
Task Progress: The original intent of this study was to test 10 long-duration crewmembers taking one of two bisphosphonate regimens: either 70 mg per week alendronate or a single infusion of 4 mg of zoledronic acid. After the study began testing in 2009, the Johnson Space Center (JSC) Committee for the Protection of Human Subjects (CPHS) determined that only alendronate would be offered to U.S. crewmembers, while both dosing options could be offered to International Partners. It was further stipulated that only 7 alendronate subjects would be allowed. We have now completed testing on all 7 of these alendronate subjects. No further subjects will be tested with bisphosphonates.

All scheduled testing sessions for the 7 treated subjects—pre-flight, in-flight, and post-flight--have been completed. Dual-energy X-ray absorptiometry (DXA), pQCT (peripheral QCT), quantitative computed tomography (QCT), and blood and urine data have been collated and analyses of the major parameters of interest have been performed through R+30, including statistical analyses. These results were published in June 2013 in the journal Osteoporosis International (LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith SM, Evans H, Spector E, Ploutz-Snyder R, et al. (2013). Bisphosphonates as a supplement to exercise to protect bone during long-duration space flight. Osteoporosis International 24(7): 2105-2114). In addition, results from these 7 subjects were presented in March 2013 at the NASA Human Research Program Workshop in Moody Gardens, Galveston, TX. Work continues on analysis of data through the R+12-month time point, as well as analysis of additional data parameters not previously reported.

In 2011, the study obtained approval to add a new control group, consisting of approximately 10 ISS crewmembers not taking bisphosphonates, but otherwise participating in essentially the same pre-, in-, and post-flight testing as the 7 treated subjects. The new control group should allow us to distinguish the relative effects of bisphosphonates vs. the confounder of Advanced Resistive Exercise Device (ARED) exercise, particularly at the level of trabecular vs. cortical bone. (All treated subjects in this study have used the ARED device, whereas our previous control group used the older IRED or other resistive exercise device, capable of much lower loads than ARED.) Testing on this new control group began in 2012, and, to date, 9 crewmembers have consented to participate. Of these, 5 crewmembers have returned from ISS flights. Two of these have completed all post-flight testing through R+1 year and the remaining 3 have completed post-flight testing through R+30 days. One additional subject will return from ISS in September 2014 and 3 more will launch by May 2015. Informed consent briefings continue in an effort to recruit a 10th control subject and possibly 1 or 2 “insurance” subjects. It is anticipated that the control group will complete testing in late 2016 or early 2017.

All testing to date for the first 5 control subjects, including QCT, DXA, pQCT, abdominal ultrasound, and blood and urine testing, has been completed on schedule and without incident.

Bibliography Type: Description: (Last Updated: 10/15/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford LC, Smith SM, Evans HJ, Spector ER, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H. "Bisphosphonate ISS Flight Experiment." 36th Annual Meeting of the American Society for Bone and Mineral Research, Houston, Texas, September 12-15, 2014.

J Bone Miner Res 2014 Sep;29(Suppl 1). , Sep-2014

Project Title:  Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021 Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 08/31/2015  
Task Last Updated: 08/29/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   LeBlanc, Adrian  Ph.D. / Universities Space Research Association 
Address:  Division of Space Life Sciences  
3600 Bay Area Blvd 
Houston , TX 77058 
Email: adleblanc2@gmail.com 
Phone: 281-244-2012  
Congressional District: 22 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Universities Space Research Association 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jones, Jeffrey  Baylor College of Medicine 
Shapiro, Jay  M.D. Kennedy Krieger Institute 
Lang, Tom  Ph.D. University of California at San Francisco 
Shackelford, Linda  M.D. NASA Johnson Space Center 
Smith, Scott  Ph.D. NASA-Johnson Space Center 
Evans, Harlan  Ph.D. Wyle Laboratories 
Spector, Elisabeth  Wyle Laboratories 
Sibonga, Jean  Ph.D. Universities Space Research Association (USRA) 
Nakamura, Toshitaka  M.D., Ph.D. University of Occupational and Environmental Health 
Kohri, Kenjiro  M.D., Ph.D. Nagoya City University 
Ohshima, Hiroshi  M.D., Ph.D. Japan Aerospace Exploration Agency (JAXA) 
Keyak, Joyce  University of California, Irvine 
Key Personnel Changes / Previous PI: August 2013 Report: Dr. Joyce Keyak (University of California at Irvine) has been added as a Co-Investigator. Dr. Keyak provides expertise in the area of Finite Element Modeling using hip QCT scans, and she is a co-author of presentations and publications resulting from this flight study. Toshio Matsumoto, M.D., Ph.D., is the Japanese Co-Principal Investigator of this study, a joint project between NASA and JAXA. Dr. Matsumoto is affiliated with the Department of Medicine and Regulatory Sciences, University of Tokushima Graduate School of Medicine. His contact information is: Phone 81-88-633-7119/Fax 81-88-633-7407; Toshimat@clin.med.tokkushima-u.ac.jp .
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Maher, Jacilyn  
Center Contact:  
jacilyn.maher56@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: Yes 
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) Osteo07:We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight (IRP Rev E)
Flight Assignment/Project Notes: ISS

NOTE: End date is 8/31/2015 per HRP Master Task List dtd 7/12/11 (Ed., 8/4/11)

NOTE: Extended to 9/30/2013 per PI (Ed., 11/5/2010)

Task Description: The purpose of this Supplementary Medical Objective is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens will be tested: (1) an oral dose of 70 mg alendronate taken weekly during flight and (2) and I.V. dose of zoledronic acid 4 mg, administered just once approximately 45 days before flight. Our rationale for including both alendronate and zoledronic acid is that two dosing options will: maximize crew participation, increase the countermeasure options available to flight surgeons, increase scientific opportunities, and minimize the effects of operational and logistical constraints. Use of both oral and I.V. options can accommodate both crew and flight surgeon preferences (e.g., based on individual drug sensitivity, relevant health conditions, or other considerations). Operational and logistical constraints may favor one option versus the other. For example, stowage limits may limit use of alendronate on certain flights, while the ability to titrate the in-flight dose in response to on-orbit measurements of bone resorption would favor the weekly dosing regimen. Long-duration (e.g., 2+ year) missions would require in-flight re-dosing of I.V. zoledronic acid. The purpose of this study is not to test one dosing option versus the other. Rather, we intend to show that bisphosphonates-plus-exercise will have a measurable effect versus exercise alone in preventing space flight induced bone loss. Secondary goals will be to document the return to normal bone remodeling post-flight in crewmembers who took bisphosphonates.

Research Impact/Earth Benefits: While the primary purpose of this research is to develop a countermeasure to protect crewmembers against bone loss during long duration spaceflight, this research may provide insight into the mechanisms and prevention of bone atrophy in other disuse conditions.

Task Progress & Bibliography Information FY2014 
Task Progress: The original intent of this study was to test 10 long-duration crewmembers taking one of two bisphosphonate regimens: either 70 mg per week alendronate or a single infusion of 4 mg of zoledronic acid. After the study began testing in 2009, the JSC CPHS determined that only alendronate would be offered to U.S. crewmembers, while both dosing options could be offered to International Partners. It was further stipulated that only 7 alendronate subjects would be allowed. We have now completed testing on all 7 of these alendronate subjects . No further subjects will be tested with bisphosphonates.

All scheduled testing sessions for the 7 treated subjects—pre-flight, in-flight, and post-flight--have been completed. DXA, pQCT, QCT and blood and urine data have been collated and analyses of the major parameters of interest have been performed through R+30, including statistical analyses. These results were published in June 2013 in the journal Osteoporosis International (LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith SM, Evans H, Spector E, Ploutz-Snyder R, et al. (2013). Bisphosphonates as a supplement to exercise to protect bone during long-duration space flight. Osteoporosis International 24(7): 2105-2114). In addition, results from these 7 subjects were presented in March 2013 at the NASA Human Research Program Workshop in Moody Gardens, Galveston, TX. Work continues on analysis of data through the R+12-month time point, as well as analysis of additional data parameters not previously reported.

In 2011, the study obtained approval to add a new control group, consisting of approximately 10 ISS crewmembers not taking bisphosphonates, but otherwise participating in essentially the same pre-, in- and post-flight testing as the 7 treated subjects. The new control group should allow us to distinguish the relative effects of bisphosphonates vs. the confounder of ARED exercise, particularly at the level of trabecular vs. cortical bone. (All treated subjects in this study have used the ARED device, whereas our previous control group used the older IRED or other resistive exercise device, capable of much lower loads than ARED.) Testing on this new control group began in 2012, and, to date, 9 crewmembers have consented to participate. Of these, 3 crewmembers have returned from ISS flights and are in the process of completing post-flight testing. One additional subject will return from ISS in November 2013 and the remaining 5 will launch by the end of 2014. Informed consent briefings continue in an effort to recruit a 10th control subject and possibly 1 or 2 “insurance” subjects. It is anticipated that the control group will complete testing in approximately 2016.

All testing to date for the first 4 control subjects, including QCT, DXA, pQCT, abdominal ultrasound and blood and urine testing, has been completed on schedule and without incident.

Bibliography Type: Description: (Last Updated: 10/15/2019) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Leblanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith SM, Evans H, Spector E, Ploutz-Snyder R, Sibonga J, Keyak J, Nakamura T, Kohri K, Ohshima H. "Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight." Osteoporosis International. 2013 Jul;24(7):2105-14. Epub 2013 Jan 19. http://dx.doi.org/10.1007/s00198-012-2243-z ; PubMed PMID: 23334732 , Jul-2013
Project Title:  Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021 Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 08/31/2015  
Task Last Updated: 09/21/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   LeBlanc, Adrian  Ph.D. / Universities Space Research Association 
Address:  Division of Space Life Sciences  
3600 Bay Area Blvd 
Houston , TX 77058 
Email: adleblanc2@gmail.com 
Phone: 281-244-2012  
Congressional District: 22 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Universities Space Research Association 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jones, Jeffrey  Baylor College of Medicine 
Shapiro, Jay  M.D. Kennedy Krieger Institute 
Lang, Tom  Ph.D. University of California at San Francisco 
Shackelford, Linda  M.D. NASA Johnson Space Center 
Smith, Scott  Ph.D. NASA-Johnson Space Center 
Evans, Harlan  Ph.D. Wyle Laboratories 
Spector, Elisabeth  Wyle Laboratories 
Sibonga, Jean  Ph.D. Universities Space Research Association (USRA) 
Nakamura, Toshitaka  M.D., Ph.D. University of Occupational and Environmental Health 
Kohri, Kenjiro  M.D., Ph.D. Nagoya City University 
Ohshima, Hiroshi  M.D., Ph.D. Japan Aerospace Exploration Agency (JAXA) 
Key Personnel Changes / Previous PI: Toshio Matsumoto, M.D., Ph.D., is the Japanese Co-Principal Investigator of this study, a joint project between NASA and JAXA. Dr. Matsumoto is affiliated with the Department of Medicine and Regulatory Sciences, University of Tokushima Graduate School of Medicine. His contact information is: Phone 81-88-633-7119/Fax 81-88-633-7407; Toshimat@clin.med.tokkushima-u.ac.jp
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Maher, Jacilyn  
Center Contact:  
jacilyn.maher56@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: Yes 
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) Osteo07:We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight (IRP Rev E)
Flight Assignment/Project Notes: ISS

NOTE: End date is 8/31/2015 per HRP Master Task List dtd 7/12/11 (Ed., 8/4/11)

NOTE: Extended to 9/30/2013 per PI (Ed., 11/5/2010)

Task Description: The purpose of this Supplementary Medical Objective is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens will be tested: (1) an oral dose of 70 mg alendronate taken weekly during flight and (2) and I.V. dose of zoledronic acid 4 mg, administered just once approximately 45 days before flight. Our rationale for including both alendronate and zoledronic acid is that two dosing options will: maximize crew participation, increase the countermeasure options available to flight surgeons, increase scientific opportunities, and minimize the effects of operational and logistical constraints. Use of both oral and I.V. options can accommodate both crew and flight surgeon preferences (e.g., based on individual drug sensitivity, relevant health conditions, or other considerations). Operational and logistical constraints may favor one option versus the other. For example, stowage limits may limit use of alendronate on certain flights, while the ability to titrate the in-flight dose in response to on-orbit measurements of bone resorption would favor the weekly dosing regimen. Long-duration (e.g., 2+ year) missions would require in-flight re-dosing of I.V. zoledronic acid. The purpose of this study is not to test one dosing option versus the other. Rather, we intend to show that bisphosphonates-plus-exercise will have a measurable effect versus exercise alone in preventing space flight induced bone loss. Secondary goals will be to document the return to normal bone remodeling post-flight in crewmembers who took bisphosphonates.

Research Impact/Earth Benefits: While the primary purpose of this research is to develop a countermeasure to protect crewmembers against bone loss during long duration spaceflight, this research may provide insight into the mechanisms and prevention of bone atrophy in other disuse conditions.

Task Progress & Bibliography Information FY2013 
Task Progress: The original intent of this study was to test 10 long-duration crewmembers taking one of two bisphosphonate regimens: either 70 mg per week alendronate or a single infusion of 4 mg of zoledronic acid. After the study began testing in 2009, the JSC CPHS determined that only alendronate would be offered to U.S. crewmembers, while both dosing options could be offered to International Partners. It was further stipulated that only 5 alendronate subjects, plus 2 insurance subjects, would be allowed. We have now completed testing on all 7 of these alendronate subjects (with the exception of R+12mo testing on the last 2 subjects, which will take place in December 2012). No further subjects will be tested with bisphosphonates.

All scheduled testing sessions for the 7 treated subjects—pre-flight, in-flight and post-flight--have been completed. The urine specimens for two of the seven however have not been returned to Earth because of the cancellation of the Shuttle program. We expect return of these samples on an upcoming Space-X resupply mission in late 2012. DXA, pQCT, QCT, and blood and urine data have been collated and preliminary analyses of the major parameters of interest have been performed, including some initial statistical analyses. Preliminary results from these 7 subjects were presented in a poster session at the February 2012 Human Research Program Investigators' Workshop in Houston, TX. The Japanese Principal Investigator, Dr. Toshio Matsumoto, plans to give an oral presentation of our results at the September 2012 meeting of the American Society for Bone and Mineral Research. In addition, Dr. LeBlanc gave oral presentations summarizing these results at the International Society of Gravitational Physiology/ESA Conference in Scotland (June 2012), and the ISS Research and Development Conference held in Denver, Colorado (June 2012).

Last year, we reported that the study had obtained approval to add a new control group to the study, consisting of approximately 10 ISS crewmembers not taking bisphosphonates, but otherwise participating in essentially the same pre-, in-, and post-flight testing as the 7 treated subjects. The new control group should allow us to distinguish the relative effects of bisphosphonates vs. the confounder of ARED (Advanced Resistive Exercise Device) exercise, particularly at the level of trabecular vs. cortical bone. ((All treated subjects in this study have used the ARED device, whereas our previous control group used the older IRED (Interim Resistive Exercise Device) or other resistive exercise device, capable of much lower loads than ARED.)) Testing on this new control group began in 2012, with the first subject in this group completing a 6-month ISS flight in September, 2012. Two additional subjects are launching later this year, and 2 more have consented to participate. Three other crewmembers have been briefed but have not yet indicated whether they will participate. Depending on participation levels by the eligible ISS crewmembers, it is anticipated that this group will complete testing in approximately 2015.

All testing to date for the first 3 control subjects, including QCT, DXA, pQCT, abdominal ultrasound, and blood and urine testing, has been completed on schedule and without incident.

Bibliography Type: Description: (Last Updated: 10/15/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith S, Evans H, Spector E, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H. "Antiresorptive Countermeasure For Spaceflight Bone Loss: Preliminary Results." 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012.

2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012. , Feb-2012

Abstracts for Journals and Proceedings Matsumoto T, LeBlanc A, Jones J, Shapiro J, Lang T, Shackelford L, Smith S, Evans H, Spector E, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H. "Prevention of Bone Loss during Spaceflight by Bisphosphonate." 2012 Annual Meeting of the American Society for Bone and Mineral Research, Minneapolis, Minnesota, October 12-15, 2012.

J Bone Miner Res 2011;27(Suppl 1):S70-1. , Oct-2012

Project Title:  Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021 Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 08/31/2015  
Task Last Updated: 08/26/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   LeBlanc, Adrian  Ph.D. / Universities Space Research Association 
Address:  Division of Space Life Sciences  
3600 Bay Area Blvd 
Houston , TX 77058 
Email: adleblanc2@gmail.com 
Phone: 281-244-2012  
Congressional District: 22 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Universities Space Research Association 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jones, Jeffrey  NASA Johnson Space Center 
Shapiro, Jay  M.D. Kennedy Krieger Institute 
Lang, Tom  Ph.D. University of California at San Francisco 
Kozlovskaya, Inessa  M.D. Institute of Biomedical Problems 
Shackelford, Linda  M.D. NASA Johnson Space Center 
Smith, Scott  Ph.D. NASA-Johnson Space Center 
Evans, Harlan  Ph.D. Wyle Laboratories 
Spector, Elisabeth  Wyle Laboratories 
Sibonga, Jean  Ph.D. Universities Space Research Association (USRA) 
Nakamura, Toshitaka  M.D., Ph.D. University of Occupational and Environmental Health 
Kohri, Kenjiro  M.D., Ph.D. Nagoya City University 
Ohshima, Hiroshi  M.D., Ph.D. Japan Aerospace Exploration Agency (JAXA) 
Key Personnel Changes / Previous PI: Toshio Matsumoto, M.D., Ph.D., is the Japanese Co-Principal Investigator of this study, a joint project between NASA and JAXA. Dr. Matsumoto is affiliated with the Department of Medicine and Regulatory Sciences, University of Tokushima Graduate School of Medicine. His contact information is: Phone 81-88-633-7119/Fax 81-88-633-7407; Toshimat@clin.med.tokkushima-u.ac.jp
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Baumann, David  
Center Contact:  
david.k.baumann@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: Yes 
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) Osteo07:We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight (IRP Rev E)
Flight Assignment/Project Notes: ISS

NOTE: End date is 8/31/2015 per HRP Master Task List dtd 7/12/11 (Ed., 8/4/11)

NOTE: Extended to 9/30/2013 per PI (Ed., 11/5/2010)

Task Description: The purpose of this Supplementary Medical Objective is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens will be tested: (1) an oral dose of 70 mg alendronate taken weekly during flight and (2) and I.V. dose of zoledronic acid 4 mg, administered just once approximately 45 days before flight. Our rationale for including both alendronate and zoledronic acid is that two dosing options will: maximize crew participation, increase the countermeasure options available to flight surgeons, increase scientific opportunities, and minimize the effects of operational and logistical constraints. Use of both oral and I.V. options can accommodate both crew and flight surgeon preferences (e.g., based on individual drug sensitivity, relevant health conditions, or other considerations). Operational and logistical constraints may favor one option versus the other. For example, stowage limits may limit use of alendronate on certain flights, while the ability to titrate the in-flight dose in response to on-orbit measurements of bone resorption would favor the weekly dosing regimen. Long-duration (e.g., 2+ year) missions would require in-flight re-dosing of I.V. zoledronic acid. The purpose of this study is not to test one dosing option versus the other. Rather, we intend to show that bisphosphonates-plus-exercise will have a measurable effect versus exercise alone in preventing space flight induced bone loss. Secondary goals will be to document the return to normal bone remodeling post-flight in crewmembers who took bisphosphonates.

Research Impact/Earth Benefits: While the primary purpose of this research is to develop a countermeasure to protect crewmembers against bone loss during long duration spaceflight, this research may provide insight into the mechanisms and prevention of bone atrophy in other disuse conditions.

Task Progress & Bibliography Information FY2012 
Task Progress: The original intent of this study was to test 10 long-duration crewmembers taking one of two bisphosphonate regimens: either 70 mg per week alendronate or a single infusion of 4 mg of zoledronic acid. After the study began testing in 2009, the JSC CPHS determined that only alendronate would be offered to U.S. crewmembers, while both dosing options could be offered to International Partners. It was further mandated that only 5 alendronate subjects, plus 2 insurance subjects, would be allowed. We have now enrolled all 7 of these alendronate subjects, and no further subjects will be tested with bisphosphonates. Of these 7 subjects, 5 have completed ISS flights. Four subjects have completed all post-flight testing through R+1 year, while the fifth has completed post-flight testing through R+30. The final 2 subjects are still in flight, and will return later this year.

All scheduled testing sessions for the 7 enrolled subjects—pre-flight, in-flight and post-flight--have been completed on time. DXA, pQCT, QCT and blood and urine data have been collated and preliminary analyses of the major parameters of interest have been performed, including some initial statistical analyses. Preliminary results (n=4) were presented in a poster presentation at the annual International Academy of Astronautics (IAA) Humans in Space symposium in April of 2011, and a similar poster (n=5) will be presented at the annual meeting of the American Society for Bone and Mineral Research in September, 2011.

A recent development in this project is the addition of a new control group to the study, which will consist of approximately 10 ISS crewmembers who will not take bisphosphonates, but who will participate in essentially the same pre-, in- and post-flight testing as the previous subjects. The reason for the new control group is that all 7 of the bisphosphonate subjects have exercised on ISS using the new Advanced Resistive Exercise Device (ARED), while the 14 historical controls all exercised using the older Interim Resistive Exercise Device (IRED). The skeletal loading capabilities are much greater with the ARED, and preliminary DXA results suggest that ARED may, in fact, be more beneficial than IRED for the preservation of bone mineral density. Because neither QCT nor pQCT data have been obtained on any crewmembers using ARED alone, the effects of bisphosphonates + ARED vs. ARED alone on compartmental bone loss, bone structure, and bone strength cannot be determined at this point. The addition of 10 new control subjects, all using ARED, should allow us to distinguish the relative effects of bisphosphonates vs. the confounder of ARED exercise, particularly at the level of trabecular vs. cortical bone. Testing on this new control group is scheduled to begin in 2012. Depending on participation levels by the eligible ISS crewmembers, it is anticipated that this group will complete testing in approximately 2015.

Bibliography Type: Description: (Last Updated: 10/15/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford LC, Smith SM, Evans HJ, Spector ER, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H. "Preliminary Results of Bisphosphonate ISS Flight Experiment." 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 LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Smith SM, Shackelford L, Sibonga J, Evans H, Spector E, Nakamura T, Kohri K, Ohshima H. "Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss." 2010 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 3-5, 2010.

2010 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 3-5, 2010. Abstract #1094. , Feb-2010

Abstracts for Journals and Proceedings LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford LC, Smith SM, Evans HJ, Spector ER, Ploutz-Snyder R, Sibonga J, Nakamura T, Kohri K, Ohshima H. "Antiresorptive Treatment for Spaceflight Induced Bone Atrophy: Preliminary Results." 33rd Annual Meeting of the American Society for Bone and Mineral Research, San Diego, California, September 16-20, 2011.

33rd Annual Meeting of the American Society for Bone and Mineral Research, San Diego, California, September 16-20, 2011. , Sep-2011

Project Title:  Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021 Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 08/31/2015  
Task Last Updated: 05/21/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   LeBlanc, Adrian  Ph.D. / Universities Space Research Association 
Address:  Division of Space Life Sciences  
3600 Bay Area Blvd 
Houston , TX 77058 
Email: adleblanc2@gmail.com 
Phone: 281-244-2012  
Congressional District: 22 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Universities Space Research Association 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jones, Jeffrey  NASA Johnson Space Center 
Shapiro, Jay  M.D. Kennedy Krieger Institute 
Lang, Tom  Ph.D. University of California at San Francisco 
Kozlovskaya, Inessa  M.D. Institute of Biomedical Problems 
Shackelford, Linda  M.D. NASA Johnson Space Center 
Smith, Scott M. Ph.D. NASA-Johnson Space Center 
Evans, Harlan  Ph.D. Wyle Laboratories 
Spector, Elisabeth  Wyle Laboratories 
Sibonga, Jean  Ph.D. Universities Space Research Association (USRA) 
Nakamura, Toshitaka  M.D., Ph.D. University of Occupational and Environmental Health 
Kohri, Kenjiro  M.D., Ph.D. Nagoya City University 
Ohshima, Hiroshi  M.D., Ph.D. Japan Aerospace Exploration Agency (JAXA) 
Key Personnel Changes / Previous PI: Toshio Matsumoto, M.D., Ph.D., is the Japanese Co-Principal Investigator of this study, a joint project between NASA and JAXA. Dr. Matsumoto is affiliated with the Department of Medicine and Regulatory Sciences, University of Tokushima Graduate School of Medicine. His contact information is: Phone 81-88-633-7119/Fax 81-88-633-7407; Toshimat@clin.med.tokkushima-u.ac.jp.
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor: Goodwin, Thomas  
Center Contact:  
thomas.j.goodwin@nasa.gov 
Solicitation / Funding Source: Directed Research 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: Yes 
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) Osteo07:We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight (IRP Rev E)
Flight Assignment/Project Notes: ISS NOTE: End date is 8/31/2015 per HRP Master Task List dtd 7/12/11 (Ed., 8/4/11)

NOTE: Extended to 9/30/2013 per PI (11/5/2010)

Task Description: The purpose of this Supplementary Medical Objective is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens will be tested: (1) an oral dose of 70 mg alendronate taken weekly during flight and (2) and I.V. dose of zoledronic acid 4 mg, administered just once approximately 45 days before flight. Our rationale for including both alendronate and zoledronic acid is that two dosing options will: maximize crew participation, increase the countermeasure options available to flight surgeons, increase scientific opportunities, and minimize the effects of operational and logistical constraints. Use of both oral and I.V. options can accommodate both crew and flight surgeon preferences (e.g., based on individual drug sensitivity, relevant health conditions, or other considerations). Operational and logistical constraints may favor one option versus the other. For example, stowage limits may limit use of alendronate on certain flights, while the ability to titrate the in-flight dose in response to on-orbit measurements of bone resorption would favor the weekly dosing regimen. Long-duration (e.g., 2+ year) missions would require in-flight re-dosing of I.V. zoledronic acid. The purpose of this study is not to test one dosing option versus the other. Rather, we intend to show that bisphosphonates-plus-exercise will have a measurable effect versus exercise alone in preventing space flight induced bone loss. Secondary goals will be to document the return to normal bone remodeling post-flight in crewmembers who took bisphosphonates.

Research Impact/Earth Benefits: While the primary purpose of this research is to develop a countermeasure to protect crewmembers against bone loss during long duration spaceflight, this research may provide insight into the mechanisms and prevention of bone atrophy in other disuse conditions.

Task Progress & Bibliography Information FY2009 
Task Progress: The first research subject/crewmember is currently in space aboard the ISS. This subject is taking a weekly oral dose of alendronate. All scheduled preflight and inflight measurments and data collection have occured according to plan.

To date, the following activities have been accomplished:

1. Informed Consent Briefings;17 crewmembers.

2. Signed Consent Forms; 4 Prime and 2 Backup crew have currently volunteered to prticipate in this experiment.

3. Science Training; 8 crewmembers.

4. Urine and Pill Ingestion Training; 8 crewmembers.

5. Alendronate Tolerance Testing; 6 crewmembers.

6. Pre-Dosing Blood and Urine Collections (L-45); 6 crewmembers.

7. Post-Dosing Blood and Urine Collections (L-10); 1 crewmember.

8. Pre-Flight DXA; 2 crewmembers.

9. Pre-Flight pQCT; 2 crewmembers.

10. Pre-Flight High-Resolution QCT; 2 crewmembers.

11. Pre-Flight Renal Ultrasound; 2 crewmembers.

12. Pre-Flight Alendronate Dosing (L-17 to L-3); 2 crewmembers.

13. Pre-Flight Ca and Vit D supplementation; 2 crewmembers.

14. In-Flight Alendronate Dosing; 1 crewmember (in progress).

15. In-Flight Urine Collections; 1 crewmember (in progress).

Bibliography Type: Description: (Last Updated: 10/15/2019) 

Show Cumulative Bibliography Listing
 
 None in FY 2009
Project Title:  Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021 Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 09/30/2010  
Task Last Updated: 11/27/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   LeBlanc, Adrian  Ph.D. / Universities Space Research Association 
Address:  Division of Space Life Sciences  
3600 Bay Area Blvd 
Houston , TX 77058 
Email: adleblanc2@gmail.com 
Phone: 281-244-2012  
Congressional District: 22 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Universities Space Research Association 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jones, Jeffrey  NASA Johnson Space Center 
Shapiro, Jay  Kennedy Krieger Institute 
Lang, Tom  University of California at San Francisco 
Kozlovskaya, Inessa  Institute of Biomedical Problems  
Shackelford, Linda  NASA Johnson Space Center 
Smith, Scott M.  NASA Johnson Space Center 
Evans, Harlan  Wyle Laboratories 
Spector, Elisabeth  Wyle Laboratories 
Sibonga, Jean  Universities Space Research Association (USRA) 
Nakamura, Toshitaka  University of Occupational and Environmental Health 
Kohri, Kenjiro  Nagoya City University 
Ohshima, Hiroshi  Japan Aerospace Exploration Agency (JAXA) 
Key Personnel Changes / Previous PI: Toshio Matsumoto, M.D., Ph.D., is the Japanese Co-Principal Investigator of this study, a joint project between NASA and JAXA. Dr. Matsumoto is affiliated with the Department of Medicine and Regulatory Sciences, University of Tokushima Graduate School of Medicine. His contact information is: Phone 81-88-633-7119/Fax 81-88-633-7407; Toshimat@clin.med.tokkushima-u.ac.jp .
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: Directed Research 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: Yes 
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) Osteo07:We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight (IRP Rev E)
Flight Assignment/Project Notes: ISS 18, 19, 20

Task Description: The purpose of this Supplementary Medical Objective is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens will be tested: (1) an oral dose of 70 mg alendronate taken weekly during flight and (2) and I.V. dose of zoledronic acid 4 mg, administered just once approximately 45 days before flight. Our rationale for including both alendronate and zoledronic acid is that two dosing options will: maximize crew participation, increase the countermeasure options available to flight surgeons, increase scientific opportunities, and minimize the effects of operational and logistical constraints. Use of both oral and I.V. options can accommodate both crew and flight surgeon preferences (e.g., based on individual drug sensitivity, relevant health conditions, or other considerations). Operational and logistical constraints may favor one option versus the other. For example, stowage limits may limit use of alendronate on certain flights, while the ability to titrate the in-flight dose in response to on-orbit measurements of bone resorption would favor the weekly dosing regimen. Long-duration (e.g., 2+ year) missions would require in-flight re-dosing of I.V. zoledronic acid. The purpose of this study is not to test one dosing option versus the other. Rather, we intend to show that bisphosphonates-plus-exercise will have a measurable effect versus exercise alone in preventing space flight induced bone loss. Secondary goals will be to document the return to normal bone remodeling post-flight in crewmembers who took bisphosphonates.

See also http://www.nasa.gov/mission_pages/station/research/experiments/239.html

Research Impact/Earth Benefits: While the primary purpose of this research is to develop a countermeasure to protect crewmembers against bone loss during long duration spaceflight, this research may provide insight into the mechanisms and prevention of bone atrophy in other disuse conditions.

Task Progress & Bibliography Information FY2007 
Task Progress: New project for FY2007.

Bibliography Type: Description: (Last Updated: 10/15/2019) 

Show Cumulative Bibliography Listing
 
 None in FY 2007