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)

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

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

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)

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.

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)

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.

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)

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.

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)

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.

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)

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.

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

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).

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