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Age-Related Changes in the Bone Marrow

Abstract

Purpose of Review

To summarize current knowledge with regards to age-related changes in the bone marrow from childhood to senility and discuss how these changes are affected in patients with osteoporosis.

Recent Findings

There is a dramatic increase in marrow fat content in females around the time of the menopause in line with a reduction in bone mass. Marrow fat content is very responsive to physiological changes in estrogen and increase in marrow fat can be reversed by estrogen replacement. Marrow fat composition, rather than content, seems to be related to insufficiency fracture and diabetes.

Summary

MR imaging is a very good way of non-invasively studying marrow fat changes throughout life—both content and composition. Marrow fat content is an inverse marker of red marrow content. Red marrow content drives bone perfusion. Bone perfusion affects marrow nutrition and bone healing. Research into the fascinating bone-fat-perfusion relationship has only just began.

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References

Papers of particular interest, published recently, have been 33409 highlighted as: • Of importance •• Of major importance

  1. 1.

    Travlos GS. Normal structure, function, and histology of the bone marrow. Toxicol Pathol. 2006;34:548–65.

    Article  PubMed  Google Scholar 

  2. 2.

    Hwang S, Panicek DM. Magnetic resonance imaging of bone marrow in oncology, Part 1. Skeletal Radiol. 2007;36:913–20.

    Article  PubMed  Google Scholar 

  3. 3.

    Ellis SL, Grassinger J, Jones A, Borg J, Camenisch T, Haylock D, Bertoncello I, Nilsson SK. The relationship between bone, hemopoietic stem cells, and vasculature. Blood. 2011;118:1516–24.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    •• Guezguez B, Campbell CJ, Boyd AL, Karanu F, Casado FL, Di Cresce C, Collins TJ, Shapovalova Z, Xenocostas A, Bhatia M. Regional localization within the bone marrow influences the functional capacity of human HSCs. Cell Stem Cell. 2013;13:175–89. Human haematopoetic stem cells localizing to the trabecular bone areas show enhanced regenerative and self-renewal capacity and are molecularly distinct from those localizing to other bone areas. Osteoblasts may regulate these haematopoetic stem cells.

  5. 5.

    Köhler A, Schmithorst V, Filippi MD, Ryan MA, Daria D, Gunzer M, Geiger H. Altered cellular dynamics and endosteal location of aged early hematopoietic progenitor cells revealed by time-lapse intravital imaging in long bones. Blood. 2009;114:290–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    •• Pang WW, Schrier SL, Weissman IL. Age-associated changes in human hematopoietic stem cells. Semin Hematol. 2017;54:39–42. Possibly due to changes in aging bone marrow microenvironment, even though human HSCs increase in number, they have decreased self-renewal capacity, decreased reconstitution potential and are more myeloid-biased in their differentiation potential conferring an increased risk of developing into an age-associated diseases, such as myelodysplastic syndrome and myeloproliferative disorders.

  7. 7.

    Emery JL, Follett GF. Regression of bone-marrow haemopoiesis from the terminal digits in the foetus and infant. Br J Haematol. 1964;10:485–9.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Hartsock RJ, Smith EB, Petty CS. Normal variations with aging of the amount of hematopoetic tissue in bone marrow from the anterior iliac crest. A study made from 177 cases of sudden death examined by necropsy. Am J Clin Pathol. 1965;43:326–31.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Poulton TB, Murphy WD, Duerk JL, Chapek CC, Feiglin DH. Bone marrow reconversion in adults who are smokers: MR Imaging findings. Am J Roentgenol. 1993;161:1217–21.

    CAS  Article  Google Scholar 

  10. 10.

    •• Pansini V, Monnet A, Salleron J, Hardouin P, Cortet B, Cotten A. 3 Tesla (1) H MR spectroscopy of hip bone marrow in a healthy population, assessment of normal fat content values and influence of age and sex. J Magn Reson Imaging. 2014;39:369–76. Shows how the proximal femur is a good area to compare chronological changes in marrow fat content being relatively fat rich areas and red marrow rich areas. Fat content increased in all areas with increasing years.

  11. 11.

    Steiner RM, Mitchell DG, Rao VM, Schweitzer ME. Magnetic resonance imaging of diffuse bone marrow disease. Radiol Clin North Am. 1993;31:383–409.

    CAS  PubMed  Google Scholar 

  12. 12.

    Griffith JF, Yeung DK, Ahuja AT, Choy CW, Mei WY, Lam SS, Lam TP, Chen ZY, Leung PC. A study of bone marrow and subcutaneous fatty acid composition in subjects of varying bone mineral density. Bone. 2009;44:1092–6.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Bernard C, Liney G, Manton D, Turnbull L, Langton C. Comparison of fat quantification methods: a phantom study at 3.0T. J Magn Reson Imaging. 2008;27:192–7.

    Article  PubMed  Google Scholar 

  14. 14.

    Griffith JF, Yeung DK, Chow SK, Leung JC, Leung PC. Reproducibility of MR perfusion and (1)H spectroscopy of bone marrow. J Magn Reson Imaging. 2009;29:1438–42.

    Article  PubMed  Google Scholar 

  15. 15.

    Dunnill MS, Anderson JA, Whitehead R. Quantitative histological studies on age changes in bone. J Pathol Bacteriol. 1967;94:275–91.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Duda SH, Laniado M, Schick F, Strayle M, Claussen CD. Normal bone marrow in the sacrum of young adults: differences between the sexes seen on chemical-shift MR imaging. AJR Am J Roentgenol. 1995;164:935–40.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Griffith JF. Bone marrow changes in osteoporosis. In: Guglielmi G editor. Medical radiology, osteoporosis and bone densitometry measurements. New York: Springer; 2013.

  18. 18.

    Griffith JF. Age-related physiological changes of the bone marrow and immune system. In: Guglielmi G, Peh WCG, Guermazi A, editors. New York: Geriatric imaging. Springer; 2013. p. 891–904.

  19. 19.

    Griffith JF, Yeung DKW, Ma HT, Leung JSC, Kwok TCY, Leung PC. Bone marrow fat content in the elderly: a reversal of trend seen in younger subjects. J Magn Reson Imaging. 2012;36:225–30.

    Article  PubMed  Google Scholar 

  20. 20.

    Liney GP, Bernard CP, Manton DJ, Turnbull LW, Langton CM. Age, gender, and skeletal variation in bone marrow composition: a preliminary study at 3.0 Tesla. J Magn Reson Imaging. 2007;26:787–93.

    Article  PubMed  Google Scholar 

  21. 21.

    •• Wáng YX, Griffith JF, Deng M, Yeung DK, Yuan J. Rapid increase in marrow fat content and decrease in marrow perfusion in lumbar vertebra following bilateral oophorectomy: an MR imaging-based prospective longitudinal study. Korean J Radiol. 2015;16:154–9. Shows how bone density decreases and marrow fat increases dramatically after surgical oophorectomy.

  22. 22.

    •• Limonard EJ, Veldhuis-Vlug AG, van Dussen L, Runge JH, Tanck MW, Endert E, Heijboer AC, Fliers E, Hollak CE, Akkerman EM, Bisschop PH. Short-term effect of estrogen on human bone marrow fat. J Bone Miner Res. 2015;30:2058–66. Vertebral bone marrow fat fraction increased by 2% during the follicular phase (P = 0.033), and decrease by a comparable degree during the luteal phase. Bone marrow fat fraction decreased by 5% during hormone replacement in post-menopausal women and increased after cessation. Estrogen seems to regulate bone marrow fat independent of bone mass.

  23. 23.

    Toth MJ, Tchernof A, Sites CK, Poehlman ET. Menopause-related changes in body fat distribution. Ann NY Acad Sci. 2000;904:502–6.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Blouin K, Boivin A, Tchernof A. Androgens and body fat distribution. J Steroid Biochem Mol Biol. 2008;108:272–80.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Bredella MA, Torriani M, Ghomi RH, et al. Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women. Obesity. 2011;19:49–53.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Shih TT, Chang CJ, Hsu CY, Wei SY, Su KC, Chung HW. Correlation of bone marrow lipid water content with bone mineral density on the lumbar spine. Spine (Phila Pa 1976). 2004;29:2844–50 (15).

    Article  Google Scholar 

  27. 27.

    Gao J, Zeng S, Sun BL, Fan HM, Han LH. Menstrual blood loss and hematologic indices in healthy Chinese women. J Reprod Med. 1987;32:822–6.

    CAS  PubMed  Google Scholar 

  28. 28.

    •Schwartz AV. Marrow fat and bone: review of clinical findings. Front Endocrinol (Lausanne). 2015;6:40. Good review of the current knowledge between marrow fat and bone.

  29. 29.

    Griffith JF, Yeung DK, Leung JC, Kwok TC, Leung PC. Prediction of bone loss in elderly female subjects by MR perfusion imaging and spectroscopy. Eur Radiol. 2011;21:1160–9.

    Article  PubMed  Google Scholar 

  30. 30.

    Wehrli FW, Hopkins JA, Hwang SN, Song HK, Snyder PJ, Haddad JG. Cross-sectional study of osteopenia with quantitative MR imaging and bone densitometry. Radiology. 2000;217:527–38.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Yeung DK, Griffith JF, Antonio GE, Lee FK, Woo J, Leung PC. Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J Magn Reson Imaging. 2005;22:279–85.

    Article  PubMed  Google Scholar 

  32. 32.

    Li X, Shet K, Rodriguez JP, Pino AM, Kurhanewicz J, Schwartz A, Rosen CJ. Unsaturation level decreased in bone marrow lipids of postmenopausal women with low bone density using high resolution HRMAS NMR. J Bone Miner Res. 2012;27(Suppl):1.

    Google Scholar 

  33. 33.

    •• Patsch JM, Li X, Baum T, Yap SP, Karampinos JDC, Schwartz AV, Link Tm. Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res. 2013;28:1721–8. Insufficiency fracture patients had 1.7% lower unsaturation levels and 2.9% higher saturation levels. Diabetics had 1.3% lower unsaturation and 3.3% higher saturation levels. Diabetics with fractures had the lowest marrow unsaturation and highest saturation. Although marrow fat composition was associated with diabetes and fracture, marrow fat content did not change with diabetes or fracture.

  34. 34.

    Griffith JF, Wang YX, Zhou H, Kwong WH, Wong WT, Sun YL, Huang Y, Yeung DK, Qin L, Ahuja AT. Reduced bone perfusion in osteoporosis: likely causes in an ovariectomy rat model. Radiology. 2010;254:739–46.

    Article  PubMed  Google Scholar 

  35. 35.

    Knothe Tate ML, Niederer P, Knothe U. In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading. Bone. 1998;22:107–17.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Lichtman MA. The ultrastructure of the hemopoietic environment of the marrow: a review. Exp Hematol. 1981;9:391–410.

    CAS  PubMed  Google Scholar 

  37. 37.

    Munka V, Gregor A. Lymphatics and bone marrow. Folia Morphol (Praha). 1965;13:404–12.

    CAS  Google Scholar 

  38. 38.

    Kahn D, Weiner GJ, Ben-Haim S, Ponto LL, Madsen MT, Bushnell DL, Watkins GL, Argenyi EA, Hichwa RD. Positron emission tomographic measurement of bone marrow blood flow to the pelvis and lumbar vertebrae in young normal adults. Blood. 1994;83(4):958–63 (erratum in: Blood 1994; 15;84:3602).

    CAS  PubMed  Google Scholar 

  39. 39.

    Donahue MJ, Lu H, Jones CK, Pekar JJ, van Zijl PC. An account of the discrepancy between MRI and PET cerebral blood flow measures. A high-field MRI investigation. NMR Biomed. 2006;19:1043–54.

    PubMed  Google Scholar 

  40. 40.

    Choyke PL, Dwyer AJ, Knopp MV. Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging. 2003;17:509–20.

    Article  PubMed  Google Scholar 

  41. 41.

    Knopp EA, Cowper SE. Nephrogenic systemic fibrosis: early recognition and treatment. Semin Dial. 2008;21:123–8.

    Article  PubMed  Google Scholar 

  42. 42.

    Chen WT, Shih T, Chen RC, et al. Vertebral bone marrow perfusion evaluated with dynamic contrast-enhanced MR imaging: significance of aging and sex. Radiology. 2001;220:213–8.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Montazel JL, Divine M, Lepage E, Kobeiter H, Breil S, Rahmouni A. Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging. Radiology. 2003;229:703–9.

    Article  PubMed  Google Scholar 

  44. 44.

    Baur A, Stabler A, Bartl R, Lamerz R, Scheidler J, Reiser M. MRI gadolinium enhancement of bone marrow: age-related changes in normals and in diffuse neoplastic infiltration. Skeletal Radiol. 1997;26:414–8.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Griffith JF, Yeung DK, Antonio GE, Wong SY, Kwok TC, Woo J, Leung PC. Vertebral marrow fat content and diffusion and perfusion indexes in women with varying bone density: MR evaluation. Radiology. 2006;241:831–8.

    Article  PubMed  Google Scholar 

  46. 46.

    Griffith JF, Yeung DK, Antonio GE, Lee FK, Hong AW, Wong SY, Lau EM, Leung PC. Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy. Radiology. 2005;236:945–51.

    Article  PubMed  Google Scholar 

  47. 47.

    Savvopoulou V, Maris TG, Vlahos L, Moulopoulos LA. Differences in perfusion parameters between upper and lower lumbar vertebral segments with dynamic contrast-enhanced MRI (DCE MRI). Eur Radiol. 2008;18:1876–83.

    Article  PubMed  Google Scholar 

  48. 48.

    Griffith JF, Yeung DK, Kwok TC, Ahuja AT, Leung PC. Compromised bone perfusion in osteoporosis. J Bone Miner Res. 2008;23:1068–75.

    Article  PubMed  Google Scholar 

  49. 49.

    Wang YX, Griffith JF, Kwok AW, Leung JC, Yeung DK, Ahuja AT, Leung PC. Reduced bone perfusion in proximal femur of subjects with decreased bone mineral density preferentially affects the femoral neck. Bone. 2009;45:711–5.

    Article  PubMed  Google Scholar 

  50. 50.

    Demmler K, Otte P, Bartl R, et al. Osteopenia, marrow atrophy and capillary circulation: comparative studies of the human iliac crest and 1st lumbar vertebra. Z Orthop. 1983;121:223–7.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Chen WT, Ting-Fang Shih T, Hu CJ, Chen RC, Tu HY. Relationship between vertebral bone marrow blood perfusion and common carotid intima-media thickness in aging adults. J Magn Reson Imaging. 2004;20:811–6.

    Article  PubMed  Google Scholar 

  52. 52.

    Gurkan UA, Akkus O. The mechanical environment of bone marrow: a review. Ann Biomed Eng. 2008;36:1978–91.

    Article  PubMed  Google Scholar 

  53. 53.

    Khoo MM, Tyler PA, Saifuddin A, Padhani AR. Diffusion-weighted imaging (DWI) in musculoskeletal MRI: a critical review. Skeletal Radiol. 2011;40:665–81.

    Article  PubMed  Google Scholar 

  54. 54.

    Mills R. Self-diffusion in normal and heavy water in the range 1-45deg. J Phy Chem. 1973;77:685–8.

    CAS  Article  Google Scholar 

  55. 55.

    Lehnert A, Machann J, Helms G, Claussen CD, Schick F. Diffusion characteristics of large molecules assessed by proton MRS on a whole-body MR system. Magn Reson Imaging. 2004;22:39–46.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Ward R, Caruthers S, Yablon C, Blake M, DiMasi M, Eustace S. Analysis of diffusion changes in posttraumatic bone marrow using navigator-corrected diffusion gradients. AJR Am J Roentgenol. 2000;174:731–4.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Hillengass J, Stieltjes B, Bäuerle T, McClanahan F, Heiss C, Hielscher T, Wagner-Gund B, Habetler V, Goldschmidt H, Schlemmer HP, Delorme S, Zechmann CM. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging of bone marrow in healthy individuals. Acta Radiol. 2011;1(52):324–30.

    Article  Google Scholar 

  58. 58.

    Yeung DK, Wong SY, Griffith JF, Lau EM. Bone marrow diffusion in osteoporosis: evaluation with quantitative MR diffusion imaging. J Magn Reson Imaging. 2004;19:222–8.

    Article  PubMed  Google Scholar 

  59. 59.

    Nonomura Y, Yasumoto M, Yoshimura R, Haraguchi K, Ito S, Akashi T, Ohashi I. Relationship between bone marrow cellularity and apparent diffusion coefficient. J Magn Reson Imaging. 2001;13:757–60.

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    •Jie H, Hao F, Na LX. Vertebral bone marrow diffusivity in healthy adults at 3T diffusion-weighted imaging. Acta Radiol. 2016;57:1238–43. ADC values of the female subjects were higher than those of males. ADC values of pre-menopausal females were higher than those of post-menopausal females. ADC value was also negatively correlated with age (r = −0.334, P = 0.001), particularly among women (r = −0.581, P < 0.001). In other words, higher ADC values reflect higher red marrow content and change in accordance with changes in the cellular composition of the lumbar bone marrow.

  61. 61.

    Blebea JS, Houseni M, Torigian DA, Fan C, Mavi A, Zhuge Y, Iwanaga T, Mishra S, Udupa J, Zhuang J, Gopal R, Alavi A. Structural and functional imaging of normal bone marrow and evaluation of its age-related changes. Semin Nucl Med. 2007;37:185–94.

    Article  PubMed  Google Scholar 

  62. 62.

    Basu S, Houseni M, Bural G, Chamroonat W, Udupa J, Mishra S, Alavi A. Magnetic resonance imaging based bone marrow segmentation for quantitative calculation of pure red marrow metabolism using 2-deoxy-2-[F-18] fluoro-d-glucose-positron emission tomography: a novel application with significant implications for combined structure-function approach. Mol Imaging Biol. 2007;9:361–5.

    Article  PubMed  Google Scholar 

  63. 63.

    Fan C, Hernandez-Pampaloni M, Houseni M, Chamroonrat W, Basu S, Kumar R, Dadparvar S, Torigian DA, Alavi A. Age-related changes in the metabolic activity and distribution of the red marrow as demonstrated by -deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography. Imaging Biol. 2007;9:300–7.

    Article  Google Scholar 

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Correspondence to James F. Griffith.

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James F. Griffith declares no potential conflicts of interest.

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This article is part of the Topical Collection on Geriatrics.

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Griffith, J.F. Age-Related Changes in the Bone Marrow. Curr Radiol Rep 5, 24 (2017). https://doi.org/10.1007/s40134-017-0218-8

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Keywords

  • Bone marrow
  • Marrow perfusion
  • Marrow fat
  • Marrow diffusion
  • Magnetic resonance imaging
  • Bone densitometry