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Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates)
01.27.10

Overview | Description | Applications | Operations | Results | Publications | Images

Experiment/Payload Overview

Brief Summary

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates) will determine whether antiresorptive agents (help reduce bone loss), in conjunction with the routine inflight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS missions.

Principal Investigator

  • Adrian LeBlanc, Ph.D., Division of Space Life Sciences, Universities Space Research Association, Houston TX
  • Toshio Matsumoto, M.D., Ph.D., University of Tokushima, Kuramoto, Japan

    • Co-Investigator(s)/Collaborator(s)

  • Jeffrey A. Jones, M.D., Johnson Space Center, Houston, TX
  • Jay Shapiro, M.D., Johns Hopkins, Baltimore, MD
  • Thomas F. Lang, Ph.D., University of California - San Francisco, San Francisco, CA
  • Scott M. Smith, Ph.D., Johnson Space Center, Houston, TX
  • Linda C. Shackelford, M.D., Johnson Space Center, Houston, TX
  • Jean Sibonga, Ph.D., Universities Space Research Association, Houston, TX
  • Harlan Evans, Ph.D., Wyle Laboratories, Houston, TX
  • Elisabeth Spector, Wyle Laboratories, Houston, TX
  • Inessa Koslovskaya, M.D., Institute for Biomedical Problems, Moscow, Russia
  • Toshitaka Nakamura, M.D., Ph.D, University of Occupational and Environmental Health, Fukuoka, Japan
  • Kenjiro Kohri, M.D., Ph.D., Nagoya City University, Mizuho-ku, Nagoya, Japan
  • Hiroshi Ohshima, M.D., Ph.D., Japan Aerospace Exploration Agency, Tsukuba-shi, Japan

    • Payload Developer

    Johnson Space Center, Human Research Program, Houston, TX

    Sponsoring Agency

    National Aeronautics and Space Administration (NASA)

    Expeditions Assigned

    |18 |19/20 |21/22 |23/24 |25/26|

    Previous ISS Missions

    Bisphosphonates is a continuing investigation which began during Expedition 18.

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    Experiment/Payload Description

    Research Summary

    • The potential for loss of bone mass is one of the most important medical concerns for long-duration manned space flight with regional losses of 1-2% per month in spite of the fact that crewmembers exercise while in space. The resultant hypercalciuria (abnormally high calcium levels in urine) increases the risk of renal stone formation.


    • Bisphosphonates are a group of antiresorptive agents (help reduce bone loss) that block breakdown of bone and are used to treat osteoporosis and other disorders related to bone turnover.


    • This study will test the effectiveness of two bisphosphonates; alendronate, taken as a pill once per week before and during space flight; and zoledronic acid, given by intravenous infusion once before flight with an effect lasting for the length of the flight.


    • If shown to be an effective countermeasure to space flight-induced bone loss, bisphosphonates or other antiresorptive agents could help prevent several bone-related problems for crewmembers on ISS and on future long-duration missions. These problems include loss of bone mineral mass and the possibility of developing renal stones during or after space flight.

    Description

    The purpose of this investigation 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 of alendronate taken weekly starting 3 weeks prior to flight and then throughout the flight and (2) an I.V. dose of zoledronic acid, 4 mg, administered just once approximately 45 days before flight. The 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. Operational and logistical constraints may favor one option versus the other. The purpose of this study is not to test one dosing option versus the other. Rather, the intent is to show that bisphosphonates plus exercise will have a measurable effect versus exercise alone in preventing space flight-induced bone loss.

    The primary measurement objective of this study will be to obtain preflight and postflight Quantitative Computed Tomography (QCT) scans of the hip. The QCT scans will provide volumetric bone density information of both cortical and trabecular (spongy) bone regions of the hip. This study aims to show that bisphosphonates will significantly reduce bone mineral density loss and the increased risk of renal stone formation documented previously on untreated ISS crewmembers.

    Secondary measurement objectives will 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, inflight, and postflight urine collections to measure urinary markers of bone metabolism. Urine measurements will also be used to look at the risk for developing renal stones before, during and after flight.

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    Applications

    Space Applications

    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 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 to ameliorate other problem areas.

    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).

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    Operations

    Operational Requirements

    This experiment requires the participation of 10 long-duration crewmembers. Subjects will complete DXA scans (L-45, R+5, R+180, and R+360), pQCT scans (L-45, R+5, R+180, and R+360, R+720, and R+1080), High Resolution QCT scans (L-45, R+5, R+360), Ultrasound scans (L-180, R+30), 24-hr urine collections (L-90, L-10, R+0, R+14, R+30, R+180, R+360), and blood draws (L-90, L-10, R+0, R+14, R+30, and R+180 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. Zoledronic Acid subjects will be administered the bisphosphonate on L-45 and will conduct one or more additional blood draws for post-infusion health monitoring.

    Operational Protocols

    While in flight, Alendronate subjects will ingest a pill weekly. All subjects will conduct three urine collection sessions (flight day 4 weeks, 12 weeks, and 24 weeks). Crewmembers will also take a daily Vitamin D supplement during the duration of the mission.

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    Results/More Information

    Information Pending

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    Related Web Sites

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    Publications

    Results Publications

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      Related Publications
      • 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 Mineral Research. ;19(11):1771-1778. 2004
      • Shapiro J, Beck TJ, Mustapha B, Ruff CB, Ballard P, BrintzenhofeSzoc K, Caminis J. Zoledronic Acid Counteracts Bone Loss in the Spinal Cord Injury Model of Microgravity. Journal of Bone Mineral Research. ;19:S445. 2004
      • 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. ;2(4): 335-343. 2002
      • LeBlanc A, Schneider V, Shackelford L, West S, Oganov V, Bakulin A, Voronin L. Bone Mineral and lean tissue loss after long duration spaceflight. Journal of Musculoskeletal and Neuronal Interactactions. ;1(2):157-160. 2000
      • Bone HG, Hosking D, Devogelaer JP, 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. ;350(12):1189-1199. 2004

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      Images

      imageOne mm thick sections through the mid frontal plane of the hip, showing regions of evaluation in white superimposed on a false color image of the Quantitative Computed Tomography (QCT) data. The left hand image shows the cortical region of the femoral neck and the right hand image shows the trabecular bone regions. Courtesy image of NASA.
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      Information Provided and Updated by the ISS Program Scientist's Office
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