Subregional Assessment of Bone Loss in the Axial Skeleton in Long-term Space Flight (Subregional Bone) - 11.22.16
Bone density scans were taken preflight, soon after landing, and again one-year postflight to understand the effects of microgravity on bone loss due to long-duration space flight. This was a long-term study to understand the distribution of bone loss resulting from long-duration space flight, the recovery of bone mass postflight in the year after landing, and the extent to which these changes compare to the spread of bone mineral density measures in healthy Earth bound men and women. Science Results for Everyone
Space travellers expect to work on Mars after six months in space, but bone loss could make that risky. This long-term study found an average of 1.6-1.7 percent loss of outer bone (cortical) mass and 2.2-2.5 percent loss of inner bone (trabecular) per month during long-term spaceflight. Astronauts also experienced an average 11 percent decline in femoral bone, with only partial recovery one year after flight. This recovery came primarily in outer, rather than inner, bone density and strength. The greatest space-induced bone loss occurs in pelvis, hip, and leg bones, which should be the focus of countermeasures and surface activities designed for Mars. Experiment Details
Harry K. Genant, M.D., University of California, San Francisco, San Francisco, CA, United States
Adrian D. LeBlanc, Ph.D., Universities Space Research Association, Houston, TX, United States
Ying Lu, Ph.D., University of California, San Francisco, San Francisco, CA, United States
NASA Johnson Space Center, Human Research Program, Houston, TX, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
Human Exploration and Operations Mission Directorate (HEOMD)
ISS Expedition Duration
March 2001 - December 2002; November 2002 - May 2003; April 2003 - April 2004
Studies of bone density were conducted on Skylab and Mir.
- Subregional Bone studied the magnitude and distribution of bone loss resulting from long-duration spaceflight and assessed how bone mass is recovered postflight.
- Results of this study may have implications for the frequency of crew assignment to long-duration missions and for health issues of older astronauts.
Bone loss is one of the known risks of exposure to reduced gravity—a risk that increases with the length of stay in that environment. Although healthy bone can repair damage done to itself, researchers are yet unsure how much bone is replaced after crewmembers return to Earth. Is bone mass recovered one year after flight? Is there a difference in the subregional distribution of bone prior to flight and one year after flight? Subregional Bone measured the amount of bone lost during space flight and recovered postflight in an effort to answer these questions.
Subregional Bone hardware consisted of several devices used before and after flight. Dual-energy X-ray absorptiometry (DEXA) provided a two-dimensional measurement of the entire bone mass of the hip, spine, and heel. These measurements were compared to quantitative computed tomography (QCT), which examined cortical (the bone’s dense outer layer) and trabecular (the bone’s inner, spongy looking layer) bone separately and three dimensionally to determine the extent of bone loss in the hip and spine. QCT measurements allow researchers to determine whether loss is localized in a subregion of the bone. DEXA and QCT measurements were also compared to quantitative ultrasound (QUS) of the heel to evaluate ultrasound as a possible alternative to X-ray measurements.
Bone loss, which can increase the risk of fracture by weakening the skeleton, is an established medical risk in long-duration spaceflight. There is little information regarding which sub-regions of the most important skeletal sites, the spine and hip, are most affected. Moreover, there is little information about the extent to which the lost bone is recovered after spaceflight. This study provided the first information on space flight related compartmental bone loss (magnitude and distribution) in the axial skeleton and on the extent to which lost bone is recovered in the year following return. Furthermore, this study will have implications for the frequency of assignment to long-duration missions and for the health of the astronauts in older age. It may also be of use in designing exercise or pharmacological countermeasures to prevent bone loss.
Additionally, comparison of bone mineral density in the hip and spine between astronauts and healthy normal subjects will help to improve understanding of the prevalence of osteoporosis between different race and gender sub-groups on Earth as well as in space.
Operational Requirements and Protocols
The Subregional Bone experiment has no inflight requirements.
DEXA, QCT, and QUS scans were performed once preflight, once in the first two weeks after flight, and once more a year later. All required measurements were obtained on sixteen crew members. Tests were performed at the Baylor College of Medicine and at Johnson Space Center in Houston, TX.
Decadal Survey Recommendations
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This experiment determined the distribution of bone loss in the spine and hip in long-duration space flight using QCT and assessed how bone is recovered after return. One of the first Bioastronautics research investigations to begin on ISS, this study recruited 16 subjects between Expedition 2 and Expedition 8. The first publication in the Journal of Bone and Mineral Research (Lang et al. 2004) included eight subjects who had been back long enough to measure their bone density one year postflight. On ISS, bone mineral density was lost at an average rate of about 0.9% per month in the lumbar spine and 1.4% per month in the femoral neck. For comparison, a post-menopausal woman experiences losses of bone mineral on the order of 1% per year. The experiment provides insight into the process of bone loss because it is the first study to differentiate the loss in the cortical bone (the outer part of the bone) and the trabecular bone (the inner parts of the bone). For example, losses of mass in the cortical bone of the hip averaged around 1.6-1.7% per month whereas losses in the trabecular bone averaged 2.2-2.5% per month. In subsequent publications, Lang, et al. (2006a and 2006 b) measured the femoral neck cross section and calculated volumetric bone loss and recovery after one year on the ground after spaceflight. The authors report that bone mass and structure of the astronauts’ femurs recovered - but not fully - after a year back on Earth. Astronauts experienced an average 11% decline in femoral bone loss during spaceflight. While bone mass and volume increased back on Earth, the volumetric bone mass density did not fully recover (proximal femur is larger in size, but less mineralized and more porous than bone lost during spaceflight).
This research is included in a comprehensive discussion of the effects of spaceflight on bone health (Cavanaugh and Rice, 2007). Lang et al. (2007) discuss their results in a broader context. The large weight-bearing bones (pelvis, hips, legs) suffer greatest bone loss during spaceflight, and countermeasures and recovery therapies should focus on those areas to better protect against injuries that may be related to diminished bone strength. This research has direct applications to design of countermeasures and considerations built into surface activities for future exploration missions to Mars: after a lengthy transit (six months) in microgravity, astronauts will be expected to perform on the surface of Mars and engage in activities that place loads on large bones. This work feeds into ongoing and future experiments that monitor astronauts’ biochemical indicators of bone health and bone loss, as well as the design of diagnostic tools that may provide additional means to monitor bone size and density during exploration spaceflights (Lang et al. 2007).
In a related follow-on study, Sibonga et al. (2007, 2009) examined the bone mineral density (BMD) measurements in five regional sites for 45 crewmembers, both U.S. and Russian, that participated on 56 long duration flights of at least four months. The study population showed variable decreases in BMD across the five sites; the key result was that they could calculate an estimate for time required to restore 50% of the loss of bone in each site, and that full recovery to up to three years, much longer than the mission duration.
Keyak et al. (2009) used noninvasive quantitative computed tomography (QCT) scans and finite-element (FE) structural engineering modeling to compare the pre-flight and post-flight strength of the proximal (segment joining the hip) femur of 13 astronauts who had not taken any medical countermeasures to prevent bone loss during missions (this area of the femur typically experienced highest rate of bone loss while in space). For crewmembers exposed to microgravity for 4 to 6 months on board the ISS, finite-element calculations showed up to a 2.6% per month decrease in proximal femoral strength for loads approximating a single-limb stance, and up to a 2.0% for loads approximating a fall to the side. Over long-duration missions, the cumulative effect represented a significant reduction in bone strength. The authors stated that estimates of bone strength by this method would be more revealing since complex three-dimensional and nonlinear changes in Bone Mineral Density (BMD) were taken into account. Furthermore, QCT scans showed that while overall bone mass appeared recoverable after 1 year back on Earth, the regained bulk was from volumetric growth and the cortical bone portion, but the reductions in trabecular bone mineral density (tBMD) and strength, did not necessarily follow suit, and these losses could potentially be permanent (Lang 2006, Keyak 2009).
An affiliated study by Carpenter et al. (2010) augmented previous investigations by Lang et al. (2007) with the first long-term volumetric measurements of human bone mineral status and bone geometry of the hip and spine of an 8-crewmember subset for up to 4.5 years after long-duration spaceflights. Observed time points at landing, 1 year, and 2 to 4.5 years later showed bone recovery rate and characteristics for the spine and proximal femur in line with previous findings (Sibonga et al. 2007) in that the integral bone mineral density (iBMD) regained near preflight status over the following 2-4.5 years along with net gains in total volume and trabecular bone for the hip region. However, volumetric density measurements by QCT showed an overall trabecular bone density average decline to 88% of the preflight value over the same period, and there were no indications that this quantity of tBMD loss would eventually be recovered. Researchers also proposed that the persistent deficits in trabecular bone and bone strength coupled with natural aging osteoporosis may significantly elevate the risk for astronauts who underwent extended or repeat missions and predispose them to premature osteoporosis later in life (Carpenter 2010).
Lang TF, LeBlanc AD, Evans HJ, Lu Y, Genant HK, Yu A. Cortical and Trabecular Bone Mineral Loss from the Spine and Hip in Long-duration Spaceflight. Journal of Bone and Mineral Research. 2004; 19(6): 1006-1012. DOI: 10.1359/JBMR.040307.
Sibonga JD, Evans HJ, Sung H, Spector ER, Lang TF, Oganov VS, Bakulin AV, Shackelford LC, LeBlanc AD. Recovery of spaceflight-induced bone loss: Bone mineral density after long-duration mission as fitted with an exponential function. Bone. 2007 December; 41(6): 973-978. DOI: 10.1016/j.bone.2007.08.022.
Li W, Kezele I, Collins DL, Zijdenbos A, Keyak JH, Kornak J, Koyama A, Saeed I, LeBlanc AD, Harris TB, Lu Y, Lang TF. Voxel-based modeling and quantification of the proximal femur using inter-subject registration of quantitative CT images. Bone. 2007 November; 41(5): 888-895. DOI: 10.1016/j.bone.2007.07.006.
Keyak JH, Koyama AK, LeBlanc AD, Lu Y, Lang TF. Reduction in proximal femoral strength due to long-duration spaceflight. Bone. 2009 March; 44(3): 449-453. DOI: 10.1016/j.bone.2008.11.014. PMID: 19100348.
Lang TF, LeBlanc AD, Keyak JH. Defining and Assessing Bone Health During and After Spaceflight. Cleveland, OH: Bone Loss During Spaceflight: Etiology, Countermeasures, and Implications for Bone Health on Earth; 2007.
Sibonga JD, Evans HJ, Spector ER, Maddocks MJ, Smith SA, Shackelford LC, LeBlanc AD. Bone Health During and After Space Flight. Cleveland, OH: Bone Loss During Spaceflight: Etiology, Countermeasures, and Implications for Bone Health on Earth; 2007.
Lang TF, LeBlanc AD, Evans HJ, Lu Y. Adaptation of the Proximal Femur to Skeletal Reloading After Long-Duration Spaceflight. Journal of Bone and Mineral Research. 2006 May 29; 21(8): 1224-1230. DOI: 10.1359/JBMR.060509.
Carpenter RD, LeBlanc AD, Evans HJ, Sibonga JD, Lang TF. Long-term changes in the density and structure of the human hip and spine after long-duration spaceflight. Acta Astronautica. 2010 Jul-Aug; 67(1-2): 71-81. DOI: 10.1016/j.actaastro.2010.01.022.
Zhao Q, Li W, Li CF, Chu PW, Kornak J, Lang TF, Fang J, Lu Y. A statistical method (cross-validation) for bone loss region detection after spaceflight . Australasian Physical & Engineering Sciences in Medicine. 2010 July 15; 33(2): 163-169. DOI: 10.1007/s13246-010-0024-6.
Ground Based Results Publications
Sibonga JD, Cavanagh PR, Lang TF, LeBlanc AD, Schneider VS, Shackelford LC, Smith SM, Vico L. Adaptation of the Skeletal System During Long-Duration Spaceflight. Clinical Reviews in Bone and Mineral Metabolism. 2007 Dec; 5(4): 249-261. DOI: 10.1007/s12018-008-9012-8.
Lang TF, Li J, Harris SA, Genant HK. Assessment of vertebral bone mineral density using volumetric quantitative computed tomography. Journal of Computer Assisted Tomography. 1999; 23: 130-137.
Lang TF, Guglielmi G, Van Kuijk C, De Serio A, Cammisa M, Genant HK. Measurement of bone mineral density at the spine and proximal femur by volumetric quantitative computed tomography and dual-energy X-ray absorptiometry in elderly women with and without vertebral fractures. Bone. 2002; 30: 247-250.
Gowin W, Saparin P, Kurths J, Felsenberg D. Bone architecture assessment with measures of complexity. Acta Astronautica. 2001; 49(3-10): 171-178.
Lang TF, Augat P, Lane NE, Genant HK. Trochanteric hip fracture: strong association with spinal trabecular bone mineral density measured with quantitative computed tomography. Radiology. 1998; 209: 525-530.
Taaffe DR, Cauley JA, Danielson M, Nevitt MC, Lang TF, Bauer DC, Harris TB. Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the Health, Aging, and Body Composition Study. Journal of Bone and Mineral Research. 2001; 16(7): 1343-1352.
Li W, Kornak J, Harris TB, Keyak JH, Li CF, Lu Y, Cheng X, Lang TF. Identify fracture-critical regions inside the proximal femur using statistical parametic mapping. Bone. 2009; 44: 596-602.
Ruimerman R, Van Rietbergen B, Hilbers P, Huiskes R. A 3-dimensional computer model to simulate trabecular bone metabolism. Biorheology. 2003; 40(1-3): 315-320.
Cavanagh PR, Licata AA, Rice AJ. Exercise and Pharmocological Countermeasures for Bone Loss During Long-Duration Space Flight. Gravitational and Space Biology. 2005; 18(2): 39-58. PMID: 16038092.
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Image shows a Dual Energy X-ray Absorptiometry (DEXA) scan of a human hip bone.
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Image shows a Dual Energy X-ray Absorptiometry (DEXA) scan of a human spine.
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One 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 CT data. The left hand image shows the cortical region of the femoral neck and the right hand image shows the trabecular bone regions.
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