Spaceflight, Weightlessness, and Bone Loss — What Are We Measuring?

Journal of Bone and Mineral ResearchVolume 20, Issue 12 p. 2271-2272 Letter to the EditorFree Access Spaceflight, Weightlessness, and Bone Loss — What Are We Measuring? HH Bolotin, HH Bolotin School Of Medical Sciences, RMIT University, Bundoora, Victoria, AustraliaSearch for more papers by this author HH Bolotin, HH Bolotin School Of Medical Sciences, RMIT University, Bundoora, Victoria, AustraliaSearch for more papers by this author First published: 04 December 2009 https://doi.org/10.1359/JBMR.050822AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat To the Editor: It is the purpose of this letter to raise particular concerns about the meaningfulness of the findings of Lang et al.1 insofar as they relate to human bone mineral material losses and increased bone fragility in the "weightless" environment of protracted (4–6 months) orbital flight. It is the characteristic nature of essentially all such studies that sample sizes are necessarily small (relatively few long-duration spaceflight astronauts/cosmonauts), making statistical significance wanting, that flight durations are not the same for all, that relevant bone densitometry measurements are only made pre- and postflight (and not progressively during these spaceflights), and that QCT partial volume effects pertain to all in vivo bone structure elements that are small compared with the existing instrumental spatial resolution. Even disregarding the marginal and equivocal statistical relevance in their study of the bone losses measured by QCT and/or DXA in the trabecular regions of the spine and hip, their findings still have not shown that any actual bone mineral has been lost during these spaceflights. This looms as the common fundamental flaw in the work of Lang et al.1 and other such studies2-5 of bone material loss during lengthy orbital flight. In both QCT and DXA in vivo BMD scans, whenever, and for whatever reason(s), the anthropometrics and/or composition of any tissues (bone material included) within the scan region of interest (ROI) change between any two scans in a prospective study (in this instance, pre- and immediately postspaceflight), it has been shown6-14 that QCT-measured and DXA-measured BMD (volumetric BMD [vBMD] and areal [aBMD], respectively) always change. Put the other way around: whenever DXA-measured or QCT-measured BMD is found to change over time, it is undoubtedly the case that something in the scan ROI has changed. The question is: what has changed? Is it the actual BMC that has altered or is it that the soft tissue composition in the scan ROI (bone marrow,6, 13, 14 extraosseous fat-to-lean muscle tissue areal density ratio,7, 8 or both14) that has changed? The overriding and confounding aspect shown to be affecting such QCT/DXA studies is that one cannot be sure.14 (In the case of QCT bone densitometry, whereas voxels [pixels] imaging extraosseous tissues can usually be removed fully from the ROI of trabecular scans, those encompassing marrow cannot be eliminated [QCT spatial resolution is such that all "marrow" voxels also include trabeculae]; in the case of DXA aBMD measurements, neither marrow nor extraosseous tissues can be removed from the scan ROI.) It has been shown repeatedly and in a variety of contexts6-14 that a relatively small change in marrow composition6, 13, 14 (increased or decreased marrow cellularity [marrow reddening or yellowing, respectively]) in the trabecular regions of the spine and hip (normally greater that ∼85% marrow; less than ∼15% trabeculae by volume) can induce sizable systematic inaccuracies in both measured QCT/DXA vBMD/aBMD values that overestimate (for marrow reddening) or underestimate (for marrow yellowing) the actual true value of BMD to a like extent, without any actual change in true BMC having taken place. (True [actual] BMD is that value of vBMD and/or aBMD that would be extracted from an otherwise identical QCT/DXA BMD scan if there were no systematic measurement inaccuracy.) Central to this point, whereas no direct evidence is cited by these authors1 of actual trabecular BMC changes having taken place in otherwise normal human adults to the extent they and others2-5, 15 claim pertain over time periods of a few months, it is well established that marrow can (and does) undergo marked changes in composition over relatively short time spans.16-20 Marrow is one of the most labile tissues in the human body.6, 16 Changes in marrow composition (greater/lesser cellular content) of men and women are most pronounced in the axial (spine) and proximal ends of appendicular bones (femur)—coincidentally the self-same bone sites found to display the greatest QCT- and DXA-measured bone losses.1-5 Compositional changes in the red/yellow mix of marrow within the scan ROI alter the linear X-ray attenuation coefficient(s) of the marrow, the fundamental X-ray absorptiometric property that affects and determines both QCT and DXA BMD measurements.6-14 There is substantial direct evidence16-19, 21 that marrow composition undergoes compositional changes because of disease, infection, medication, immobilization, aging, altered exercise and athletic training regimens, dietary changes, protracted bed rest, etc., and (from the association made by Lang et al.1 between their own spaceflight study and the 17-week bed rest study of LeBlanc et al.15] long-duration spaceflight. In cases of protracted bed rest/orbital flight, the labile marrow in the spine and femoral neck turns progressively more yellow. As a result, the systematics inherent in QCT and DXA BMD measurement inaccuracies cause QCT/DXA to register correspondingly greater underestimates of the true BMD actually present, giving the illusion that true vBMD and aBMD have declined during the spaceflight. The extent of these underestimates can readily exceed those Lang et al.1 claim for bone mineral losses during spaceflights lasting 4–6 months. This is the fatal defect common to studies of human bone mineral loss in spaceflight.1-5 Because of the in vivo BMD inaccuracies inherent in QCT/DXA measurements, and as a result of changes in soft tissue anthropometrics, measured and true BMD can be substantially and systematically different. (Note that on the resumption of normal activity after the completion of previous "weightless" spaceflights, all cosmonauts/astronauts have progressively regained their "lost" bone mineral at a rate consistent with the progressive re-reddening their marrow—just as those who have completed enforced bed rest regimens and resumed normal activity.15) This is wholly consistent with no change in actual BMD having occurred during the entire protracted spaceflight and recovery time span. It would be useful to discuss what it is the measurements of Lang et al.1 have actually established, and, in so doing, possibly renew purpose and interest in studies of bone mineral loss in long-duration spaceflight. Acknowledgements This study was supported by National Health and Medical Research Council Grant 202011 (Australia). REFERENCES 1 Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A 2004 Cortical and trabecular bone mineral loss from spine and hip in long-duration spaceflight. 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