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Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight

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Abstract

Summary

We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts during 5.5 months of spaceflight.

Introduction

This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long-duration spaceflight.

Methods

We report the results from seven International Space Station (ISS) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission. All crewmembers had available for exercise a treadmill, cycle ergometer, and a resistance exercise device. Our assessment included densitometry of multiple bone regions using X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and assays of biomarkers of bone metabolism.

Results

In addition to pre- and post-flight measurements, we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device, called the interim resistance exercise device, and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device (ARED). Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained. The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including: DXA-determined losses in bone mineral density of the spine, hip, and pelvis, QCT-determined compartmental losses in trabecular and cortical bone mass in the hip, calculated measures of fall and stance computed bone strength of the hip, elevated levels of bone resorption markers, and urinary excretion of calcium.

Conclusions

The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long-duration spaceflight.

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References

  1. Rambaut PC, Johnston RS (1979) Prolonged weightlessness and calcium loss in man. Acta Astronaut 6:1113–1122

    Article  PubMed  CAS  Google Scholar 

  2. Rambaut PC, Leach CS, Whedon GD (1979) A study of metabolic balance in crewmembers of Skylab IV. Acta Astronaut 6(10):1313–1322

    Article  PubMed  CAS  Google Scholar 

  3. Whedon GD, Lutwak L, Rambaut PC, Whittle MW, Smith MC, Reid J, Leach C, Stadler CR, Sanford DD (1977) Mineral and nitrogen metabolic studies, experiment M071. In: Johnston RS, Dietlein LF (eds) Biomedical results from Skylab (NASA SP-377). National Aeronautics and Space Administration, Washington, DC, pp 164–174

    Google Scholar 

  4. Smith SM, Nillen JL, LeBlanc A, Lipton A, Demers LM, Lane HW, Leach CS (1998) Collagen cross-link excretion during space flight and bed rest. J Clin Endocrinol Metab 83(10):3584–3591

    Article  PubMed  CAS  Google Scholar 

  5. Nicogossian AE, Sawin CF, Grigoriev AI (1994) Countermeasures to space deconditioning. In: Nicogossian AE, Huntoon CL, Pool SL (eds) Space physiology and medicine, 3rd edn. Lea & Febiger, Philadelphia, pp 447–467

    Google Scholar 

  6. Oganov VS, Grigoriev AI, Voronin LI, Rakhmanov AS, Bakulin AV, Schneider VS, LeBlanc AD (1992) Bone mineral density in cosmonauts after flights lasting 4.5–6 months on the Mir orbital station. Aviakosm Ekolog Med 26(5–6):20–24

    PubMed  CAS  Google Scholar 

  7. LeBlanc A, Schneider V, Shackelford L, West S, Oganov V, Bakulin A, Voronin L (2000) Bone mineral and lean tissue loss after long duration space flight. J Musculoskelet Neuronal Interact 1:157–160

    PubMed  CAS  Google Scholar 

  8. LeBlanc A, Schneider V, Spector E, Evans H, Rowe R, Lane H, Demers L, Lipton A (1995) Calcium absorption, endogenous excretion, and endocrine changes during and after long-term bed rest. Bone 16(4 Suppl):301S–304S

    PubMed  CAS  Google Scholar 

  9. Smith SM, Wastney ME, O’Brien KO, Morukov BV, Larina IM, Abrams SA, Davis-Street JE, Oganov V, Shackelford LC (2005) Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir space station. J Bone Miner Res 20(2):208–218

    Article  PubMed  CAS  Google Scholar 

  10. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A (2004) Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 19(6):1006–1012

    Article  PubMed  Google Scholar 

  11. Keyak JH, Koyama AK, LeBlanc A, Lu Y, Lang TF (2009) Reduction in proximal femoral strength due to long-duration spaceflight. Bone 44(3):449–453

    Article  PubMed  CAS  Google Scholar 

  12. Loehr JA, Lee SM, English KL, Sibonga J, Smith SM, Spiering BA, Hagan RD (2011) Musculoskeletal adaptations to training with the advanced resistive exercise device. Med Sci Sports Exerc 43(1):146–156

    Article  PubMed  Google Scholar 

  13. Schneider SM, Amonette WE, Blazine K, Bentley J, Lee SM, Loehr JA, Moore AD Jr, Rapley M, Mulder ER, Smith SM (2003) Training with the International Space Station interim resistive exercise device. Med Sci Sports Exerc 35(11):1935–1945

    Article  PubMed  Google Scholar 

  14. Hilliard-Robertson PC, Schneider SM, Bishop SL, Guilliams ME (2003) Strength gains following different combined concentric and eccentric exercise regimens. Aviat Space Environ Med 74(4):342–347

    PubMed  CAS  Google Scholar 

  15. Smith SM, Heer MA, Shackelford L, Sibonga JD, Ploutz-Snyder L, Zwart SR (2012) Benefits for bone from resistance exercise and nutrition in long-duration spaceflight: evidence from biochemistry and densitometry. J Bone Miner Res 27(9):1896–1906

    Article  PubMed  CAS  Google Scholar 

  16. Shackelford LC, LeBlanc AD, Driscoll TB, Evans HJ, Rianon NJ, Smith SM, Spector E, Feeback DL, Lai D (2004) Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol 97(1):119–129

    Article  PubMed  CAS  Google Scholar 

  17. LeBlanc AD, Driscol TB, Shackelford LC, Evans HJ, Rianon NJ, Smith SM, Feeback DL, Lai D (2002) Alendronate as an effective countermeasure to disuse induced bone loss. J Musculoskelet Neuronal Interact 2(4):335–343

    PubMed  CAS  Google Scholar 

  18. Watanabe Y, Ohshima H, Mizuno K, Sekiguchi C, Fukunaga M, Kohri K, Rittweger J, Felsenberg D, Matsumoto T, Nakamura T (2004) Intravenous pamidronate prevents femoral bone loss and renal stone formation during 90-day bed rest. J Bone Miner Res 19(11):1771–1778

    Article  PubMed  CAS  Google Scholar 

  19. Shapiro J, Smith B, Beck T, Ballard P, Dapthary M, Brintzenhofeszoc K, Caminis J (2007) Treatment with zoledronic acid ameliorates negative geometric changes in the proximal femur following acute spinal cord injury. Calcif Tissue Int 80(5):316–322, 2007

    Article  PubMed  CAS  Google Scholar 

  20. LeBlanc AD, Evans HJ, Marsch C, Schneider V, Johnson PC, Jhingran SG (1986) Precision of dual photon absorptiometry measurements. J Nucl Med 27(8):1362–1365

    PubMed  CAS  Google Scholar 

  21. LeBlanc AD, Schneider VS, Engelbretson DA, Evans HJ (1990) Precision of regional bone mineral measurements obtained from total-body scans. J Nucl Med 31:43–45

    PubMed  CAS  Google Scholar 

  22. Spector E, LeBlanc A, Shackelford L (1995) Hologic QDR 2000 whole-body scans: a comparison of three combinations of scan modes and analysis software. Osteoporos Int 5(6):440–445

    Article  PubMed  CAS  Google Scholar 

  23. Lang TF, Leblanc AD, Evans HJ, Lu Y (2006) Adaptation of the proximal femur to skeletal reloading after long-duration spaceflight. J Bone Miner Res 21(8):1224–1230

    Article  PubMed  Google Scholar 

  24. Keyak JH, Kaneko TS, Tehranzadeh J, Skinner HB (2005) Predicting proximal femoral strength using structural engineering models. Clin Orthop Relat Res Aug 437:219–228

    Article  Google Scholar 

  25. Keyak JH, Lang TF (2012) Finite element modeling of proximal femoral load capacity under fall loading. Trans Orthop Res Soc 37:0189

    Google Scholar 

  26. Carpenter RD, LeBlanc AD, Evans HJ, Sibonga JD, Lang T (2010) Long-term changes in the density and structure of the human hip and spine after long-duration spaceflight. Acta Astronaut 67:71–81

    Article  Google Scholar 

  27. Amin S, Kopperdhal DL, Melton LJ 3rd, Achenbach SJ, Therneau TM, Riggs BL, Keaveny TM, Khosla S (2011) Association of hip strength estimates by finite-element analysis with fractures in women and men. J Bone Miner Res 26(7):1593–1600

    Article  PubMed  Google Scholar 

  28. Frost HM (1982) Mechanical determinants of bone remodeling. Metab Bone Dis Relat Res 4(4):217–229

    Article  PubMed  CAS  Google Scholar 

  29. Scheuring RA, Mathers CH, Jones JA, Wear ML (2009) Musculoskeletal injuries and minor trauma in space: incidence and injury mechanisms in U.S. astronauts. Aviat Space Environ Med 80(2):117–124

    Article  PubMed  Google Scholar 

  30. Johnston SL, Campbell MR, Scheuring R, Feiveson AH (1994) Risk of herniated nucleus pulposus among U.S. astronauts. Aviat Space Environ Med 81(6):566–574

    Article  Google Scholar 

  31. LeBlanc AD, Evans HJ, Schneider VS, Wendt RE 3rd, Hedrick TD (1994) Changes in intervertebral disc cross-sectional area with bed rest and space flight. Spine 19(7):812–817

    Article  PubMed  CAS  Google Scholar 

  32. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Tran D, Lipsky W, Choi J, Stern C, Kuyumjian R, Polk JD (2011) Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118(10):2058–2069

    Article  PubMed  Google Scholar 

  33. Pietrzyk RA, Jones JA, Sams CF, Whitson PA (2007) Renal stone formation among astronauts. Aviat Space Environ Med 78(4 Suppl):A9–A13

    PubMed  CAS  Google Scholar 

  34. Whitson PA, Pietrzyk RA, Jones JA, Nelman-Gonzalez M, Hudson EK, Sams CF (2009) Effect of potassium citrate therapy on the risk of renal stone formation during spaceflight. J Urol 182(5):2490–2496

    Article  PubMed  CAS  Google Scholar 

  35. LeBlanc AD, Spector ER, Evans HJ, Sibonga JD (2007) Skeletal responses to space flight and the bed rest analog: a review. J Musculoskelet Neuronal Interact 7(1):33–47

    PubMed  CAS  Google Scholar 

  36. Okada A, Ohshima H, Itoh Y, Yasui T, Tozawa K, Kohri K (2008) Risk of renal stone formation induced by long-term bed rest could be decreased by premedication with bisphosphonate and increased by resistive exercise. Int J Urol 15(7):630–635

    Article  PubMed  CAS  Google Scholar 

  37. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B (2012) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaw—2009 update. Aust Endod J 35(3):119–130

    Article  Google Scholar 

  38. Abrahamsen B, Einhorn TA (2012) Beyond a reasonable doubt? Bisphosphonates and atypical femur fractures. Bone 50(5):1196–1200

    Article  PubMed  CAS  Google Scholar 

  39. Feldstein AC, Black D, Perrin N, Rosales AG, Friess D, Boardman D, Dell R, Santora A, Chandler JM, Rix MM, Orwoll E (2012) Incidence and demography of femur fractures with and without atypical fractures. J Bone Miner Res 27(5):977–986.37

    Article  PubMed  Google Scholar 

  40. Lewiecki EM (2011) Safety and tolerability of denosumab for the treatment of postmenopausal osteoporosis. Drug Health Patient Safety 3:79–91

    Article  CAS  Google Scholar 

  41. Akhtar NH, Afzal MZ, Ahmed AA (2011) Osteonecrosis of jaw with the use of denosumab. J Cancer Res Ther 7(4):499–500

    Article  PubMed  Google Scholar 

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Acknowledgments

This project was supported by the Human Research Program at the National Aeronautic Space Administration and the Japan Aerospace Exploration Agency. We wish to thank Curtis Kershner, Karen Lawrence, and Michelle Lawless of Lockheed Martin for their help in managing the experiment documentation, along with Lisa King and Scott A Smith of Wyle for their help in acquiring the DXA and pQCT data. The authors would especially like to thank the astronauts who participated in this research project.

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LeBlanc, A., Matsumoto, T., Jones, J. et al. Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight. Osteoporos Int 24, 2105–2114 (2013). https://doi.org/10.1007/s00198-012-2243-z

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  • DOI: https://doi.org/10.1007/s00198-012-2243-z

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