OpNom: BisphosphonatesExperiment Overview
Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss. The purpose of the Bisphosphonates study is to determine whether an antiresorptive agent, in conjunction with the routine in-flight exercise program, protects International Space Station (ISS) crewmembers from the regional decreases in bone mineral density documented on previous ISS missions.Principal Investigator(s)
Johnson Space Center, Human Research Program, Houston, TX, United States
National Aeronautics and Space Administration (NASA)Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)Research Benefits
Space ExplorationISS Expedition Duration:
October 2008 - March 2015Expeditions Assigned
18,19/20,21/22,23/24,25/26,27/28,29/30,31/32,33/34,35/36,37/38,39/40,41/42Previous ISS Missions
This is the initial performance of this investigation.
The purpose of this investigation is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, protects International Space Station (ISS) crewmembers from the regional decreases in bone mineral density documented on previous ISS flights. Two dosing regimens were originally planned, an oral dose of 70 mg of alendronate taken weekly starting 3 weeks prior to flight and then throughout the flight and an intravenous (I.V.) dose of zoledronic acid, 4 mg, administered just once approximately 45 days before flight. However, only alendronate administration was actually tested. Control subjects, who participate in all pre-, in-, and post-flight tests, but do not ingest an antiresorptive agent, were added to control for the effects of improved exercise equipment aboard the ISS.
An interim review of the data for this study (04-E255/SMO 021) indicated that it was necessary to add a new control group whose results could be compared to those of crewmembers who have taken bisphosphonates. The original historical control group (14 crewmembers from early ISS flights) exercised using the Interim Resistive Exercise Device (IRED), while the bisphosphonate subject group (7 subjects, now complete) exercised on the newer Advanced Resistive Exercise Device (ARED). The new control group will help distinguish the relative effects of bisphosphonates versus the confounder of ARED. The control subjects will participate in essentially the same data collection protocol as the bisphosphonate group, but not take the oral or i.v. bisphosphonate.
The primary measurement objective of this study is to obtain preflight and postflight Quantitative Computed Tomography (QCT) scans of the hip. The QCT scans provide volumetric bone density information of both cortical and trabecular (spongy) bone regions of the hip. This study aims to show that bisphosphonates significantly reduces bone mineral density loss and the increased risk of renal stone formation documented previously on untreated ISS crewmembers.
Secondary measurement objectives include: preflight and postflight Dual-energy X-Ray Absorptiometry (DXA) scans of the whole body, spine, hip, and heel; preflight and postflight scans of the tibia using peripheral Quantitative Computed Tomography (pQCT); preflight and postflight abdominal/retroperitoneal ultrasound scans; preflight and postflight blood draws to measure serum markers of bone metabolism, and preflight, in flight, and postflight urine collections to measure urinary markers of bone metabolism. Urine measurements are also used to look at the risk for developing renal stones before, during and after flight.
The purpose of this investigation is to determine whether antiresorptive bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density and bone strength documented on previous ISS flights. If shown to be an effective countermeasure to space flight induced bone loss, bisphosphonates could prevent or ameliorate several potential bone-related problems identified in NASA's Critical Path Roadmap. If bisphosphonates improve the efficiency of in-flight exercise to maintain bone mass, then more crew time could be made available for other purposes.Earth Applications
The benefits of this research are primarily for space travelers. Knowledge gained from this investigation may generate useful information applicable to patients on Earth with accelerated bone loss due to disuse (e.g., spinal cord injury patients or those with prolonged immobilization).
This experiment requires the participation of long-duration crewmembers taking the drug compared with 10 control subjects. All subjects will complete DXA scans (Launch minus 45 days (L-45), Return plus 5 days (R+5), R+180, [not required for controls], and R+360), pQCT scans (L-45, R+5, R+180, [not required for controls], and R+360), high resolution QCT scans (L-45, R+5, R+360), ultrasound scans (L-180, R+30), 24-hr urine collections (L-45, R+0, early inflight, midflight, late inflight, R+30, R+360), and blood draws (L-45, R+0, R+30, and R+360). Alendronate subjects will complete an Alendronate Tolerance Test on L-180, and they will take Alendronate on L-17, L-10, and L-3.Operational Protocols
While in flight, Alendronate subjects ingest one pill weekly. All subjects conduct three urine collection sessions (4 weeks, 12 weeks, and 24 weeks). Crewmembers also take a daily Vitamin D supplement during the duration of the mission.
Jones JA, Leblanc AD, Matsumoto T, Shapiro J, Shapiro J, Lang TF, Ploutz-Snyder RJ, Shackelford LC, Smith SM, Evans HJ, Spector ER, Sibonga J, Keyak JH, Nakamura T, Kohri K, Ohshima H. Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight. Osteoporosis International. 2013 01/19/2013; epub. DOI: 10.1007/s00198-012-2243-z. PMID: 23334732.
Leblanc AD, Schneider V, Shackelford LC, West S, Oganov VS, Bakulin AV, Voronin L. Bone Mineral and lean tissue loss after long duration spaceflight. Journal of Musculoskeletal and Neuronal Interactions. 2000; 1(2): 157-160.
Leblanc AD, Driscoll TB, Shackelford LC, Evans HJ, Rianon NJ, Smith SM, Feeback DL, Lai D. Alendronate as an Effective Countermeasure to Disuse Induced Bone Loss. Journal of Musculoskeletal and Neuronal Interactions. 2002; 2(4): 335-343.
Watanabe Y, Ohshima H, Mizuno K, Sekiguchi C, Fukunaga M, Kohri K, Rittweger J, Felsenberg D, Matsumoto T, Nakamura T. Intravenous pamidronate prevents femoral bone loss and renal stone formation during 90-day bed rest. Journal of Bone and Mineral Research. 2004; 19(11): 1771-1778.
Bone HG, Hosking D, Devogelaer J, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA. Alendronate Phase III Osteoporosis Treatment Study Group. Ten years' experience with alendronate for osteoporosis in postmenopausal women. New England Journal of Medicine. 2004; 350(12): 1189-1199.
Shapiro J, Shapiro J, Beck TJ, Mustapha B, Ruff CB, Ballard P, Brintzenhofescoz K, Caminis J. Zoledronic Acid Counteracts Bone Loss in the Spinal Cord Injury Model of Microgravity. Journal of Bone and Mineral Research. 2004; 19: S445.