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). 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.