Skip to main content
SpringerLink
Log in

Bone marrow adipose tissue is associated with fracture history in anorexia nervosa

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Although bone mineral density (BMD) is decreased and fracture risk increased in anorexia nervosa, BMD does not predict fracture history in this disorder. We assessed BMD, bone microarchitecture, and bone marrow adipose tissue (BMAT) in women with anorexia nervosa and found that only BMAT was associated with fracture history.

Introduction

Anorexia nervosa (AN) is a psychiatric disorder characterized by low body weight, low BMD, and increased risk of fracture. Although BMD is reduced and fracture risk elevated, BMD as assessed by DXA does not distinguish between individuals with versus those without prior history of fracture in AN. Despite having decreased peripheral adipose tissue stores, individuals with AN have enhanced bone marrow adipose tissue (BMAT), which is inversely associated with BMD. Whether increased BMAT is associated with fracture in AN is not known.

Methods

We conducted a cross-sectional study in 62 premenopausal women, including 34 with AN and 28 normal-weight women of similar age. Fracture history was collected during patient interviews and BMD measured by DXA, BMAT by 1H-MRS, and parameters of bone microarchitecture by HR-pQCT.

Results

Sixteen women (47.1%) with AN reported prior history of fracture compared to 11 normal-weight women (39.3%, p = 0.54). In the entire group and also the subset of women with AN, there were no significant differences in BMD or parameters of bone microarchitecture in women with prior fracture versus those without. In contrast, women with AN with prior fracture had greater BMAT at the spine and femur compared to those without (p = 0.01 for both).

Conclusion

In contrast to BMD and parameters of bone microarchitecture, BMAT is able to distinguish between women with AN with prior fracture compared to those without. Prospective studies will be necessary to understand BMAT’s potential pathophysiologic role in the increased fracture risk in AN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5), 5th edn. American Psychiatric Association, Washington, DC. https://doi.org/10.1176/appi.books.9780890425596

    Book  Google Scholar 

  2. Keski-Rahkonen A, Hoek HW, Susser ES, Linna MS, Sihvola E, Raevuori A, Bulik CM, Kaprio J, Rissanen A (2007) Epidemiology and course of anorexia nervosa in the community. Am J Psychiatry 164:1259–1265

    Article  PubMed  Google Scholar 

  3. Miller KK, Grinspoon SK, Ciampa J, Hier J, Herzog D, Klibanski A (2005) Medical findings in outpatients with anorexia nervosa. Arch Intern Med 165:561–566

    Article  PubMed  Google Scholar 

  4. Vestergaard P, Emborg C, Stoving RK, Hagen C, Mosekilde L, Brixen K (2002) Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders–a nationwide register study. Int J Eat Disord 32:301–308

    Article  PubMed  Google Scholar 

  5. Faje AT, Fazeli PK, Miller KK et al (2014) Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. Int J Eat Disord 47:458–466

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nagata JM, Golden NH, Leonard MB, Copelovitch L, Denburg MR (2017) Assessment of sex differences in fracture risk among patients with anorexia nervosa: a population-based cohort study using the health improvement network. J Bone Miner Res 32:1082–1089

    Article  CAS  PubMed  Google Scholar 

  7. Frølich J, Winkler LA, Abrahamsen B, Bilenberg N, Hermann AP, Støving RK (2020) Fractures in women with eating disorders-incidence, predictive factors, and the impact of disease remission: cohort study with background population controls. Int J Eat Disord 53:1080–1087

    Article  PubMed  Google Scholar 

  8. Rigotti NA, Neer RM, Skates SJ, Herzog DB, Nussbaum SR (1991) The clinical course of osteoporosis in anorexia nervosa. A longitudinal study of cortical bone mass. JAMA 265:1133–1138

    Article  CAS  PubMed  Google Scholar 

  9. Divasta AD, Feldman HA, Gordon CM (2014) Vertebral fracture assessment in adolescents and young women with anorexia nervosa: a case series. J Clin Densitom 17:207–211

    Article  PubMed  Google Scholar 

  10. Bachmann KN, Fazeli PK, Lawson EA et al (2014) Comparison of hip geometry, strength, and estimated fracture risk in women with anorexia nervosa and overweight/obese women. J Clin Endocrinol Metab 99:4664–4673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Frølich J, Winkler LA, Abrahamsen B, Bilenberg N, Hermann AP, Støving RK (2020) Assessment of fracture risk in women with eating disorders: the utility of dual-energy x-ray absorptiometry (DXA)-Clinical cohort study. Int J Eat Disord 53:595–605

    Article  PubMed  Google Scholar 

  12. Bredella MA, Fazeli PK, Miller KK, Misra M, Torriani M, Thomas BJ, Ghomi RH, Rosen CJ, Klibanski A (2009) Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metab 94:2129–2136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ecklund K, Vajapeyam S, Feldman HA, Buzney CD, Mulkern RV, Kleinman PK, Rosen CJ, Gordon CM (2010) Bone marrow changes in adolescent girls with anorexia nervosa. J Bone Miner Res 25:298–304

    Article  PubMed  Google Scholar 

  14. Griffith JF, Yeung DK, Antonio GE, Wong SY, Kwok TC, Woo J, Leung PC (2006) Vertebral marrow fat content and diffusion and perfusion indexes in women with varying bone density: MR evaluation. Radiology 241:831–838

    Article  PubMed  Google Scholar 

  15. Schwartz AV, Sigurdsson S, Hue TF et al (2013) Vertebral bone marrow fat associated with lower trabecular BMD and prevalent vertebral fracture in older adults. J Clin Endocrinol Metab 98:2294–2300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gassert FT, Kufner A, Gassert FG et al (2022) MR-based proton density fat fraction (PDFF) of the vertebral bone marrow differentiates between patients with and without osteoporotic vertebral fractures. Osteoporos Int 33:487–496

    Article  CAS  PubMed  Google Scholar 

  17. Woods GN, Ewing SK, Schafer AL et al (2022) Saturated and unsaturated bone marrow lipids have distinct effects on bone density and fracture risk in older adults. J Bone Miner Res 37(4):700

    Article  CAS  PubMed  Google Scholar 

  18. Bredella MA, Fazeli PK, Daley SM, Miller KK, Rosen CJ, Klibanski A, Torriani M (2014) Marrow fat composition in anorexia nervosa. Bone 66:199–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cawthorn WP, Scheller EL, Learman BS et al (2014) Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab 20:368–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fazeli PK, Faje AT, Cross EJ, Lee H, Rosen CJ, Bouxsein ML, Klibanski A (2015) Serum FGF-21 levels are associated with worsened radial trabecular bone microarchitecture and decreased radial bone strength in women with anorexia nervosa. Bone 77:6–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fazeli PK, Faje AT, Bredella MA, Polineni S, Russell S, Resulaj M, Rosen CJ, Klibanski A (2019) Changes in marrow adipose tissue with short-term changes in weight in premenopausal women with anorexia nervosa. Eur J Endocrinol 180:189–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schorr M, Fazeli PK, Bachmann KN et al (2019) Differences in trabecular plate and rod structure in premenopausal women across the weight spectrum. J Clin Endocrinol Metab 104:4501–4510

    Article  PubMed  PubMed Central  Google Scholar 

  23. Polineni S, Resulaj M, Faje AT, Meenaghan E, Bredella MA, Bouxsein M, Lee H, MacDougald OA, Klibanski A, Fazeli PK (2020) Red and white blood cell counts are associated with bone marrow adipose tissue, bone mineral density, and bone microarchitecture in premenopausal women. J Bone Miner Res 35:1031–1039

    Article  CAS  PubMed  Google Scholar 

  24. Johnson J, Dawson-Hughes B (1991) Precision and stability of dual-energy X-ray absorptiometry measurements. Calcif Tissue Int 49:174–178

    Article  CAS  PubMed  Google Scholar 

  25. Popp KL, Hughes JM, Martinez-Betancourt A et al (2017) Bone mass, microarchitecture and strength are influenced by race/ethnicity in young adult men and women. Bone 103:200–208

    Article  PubMed  Google Scholar 

  26. Whittier DE, Boyd SK, Burghardt AJ, Paccou J, Ghasem-Zadeh A, Chapurlat R, Engelke K, Bouxsein ML (2020) Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography. Osteoporos Int 31:1607–1627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pistoia W, van Rietbergen B, Lochmuller EM, Lill CA, Eckstein F, Ruegsegger P (2002) Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone 30:842–848

    Article  CAS  PubMed  Google Scholar 

  28. Macneil JA, Boyd SK (2008) Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone 42:1203–1213

    Article  PubMed  Google Scholar 

  29. Fazeli PK, Bredella MA, Freedman L, Thomas BJ, Breggia A, Meenaghan E, Rosen CJ, Klibanski A (2012) Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa. J Bone Miner Res 27:1864–1871

    Article  CAS  PubMed  Google Scholar 

  30. Stone KL, Seeley DG, Lui LY, Cauley JA, Ensrud K, Browner WS, Nevitt MC, Cummings SR, Group OFR (2003) BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Miner Res 18:1947–1954

    Article  Google Scholar 

  31. Donaldson AA, Feldman HA, O’Donnell JM, Gopalakrishnan G, Gordon CM (2015) Spinal bone texture assessed by trabecular bone score in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab 100:3436–3442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Patsch JM, Li X, Baum T, Yap SP, Karampinos DC, Schwartz AV, Link TM (2013) Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res 28:1721–1728

    Article  PubMed  Google Scholar 

  33. Cummings SR, Cawthon PM, Ensrud KE, Cauley JA, Fink HA, Orwoll ES, Groups OFiMMR, Groups SoOFR (2006) BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women. J Bone Miner Res 21:1550–1556

    Article  Google Scholar 

  34. Syed FA, Oursler MJ, Hefferanm TE, Peterson JM, Riggs BL, Khosla S (2008) Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women. Osteoporos Int 19:1323–1330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Resulaj M, Polineni S, Meenaghan E, Eddy K, Lee H, Fazeli PK (2020) Transdermal estrogen in women with anorexia nervosa: an exploratory pilot study. JBMR Plus 4:e10251

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the nurses and bionutritionists of the MGH Translational and Clinical Research Center for their expert care. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Funding

This work was supported in part by the following grants from the National Institutes of Health:

• UL 1TR002541 (The Harvard Clinical and Translational Science Center, National Center for Advancing Translational Sciences)

• UL1 RR025758 (Harvard Clinical and Translational Science Center)

• 1S10RR023405 (National Center for Research Resources)

• NIH grants: R24 DK084970, P30 DK040561, K24DK109940, R01 HD099139

Author information

Authors and Affiliations

  1. Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA

    T. Dang, A. T. Faje, E. Meenaghan, A. Klibanski & P. K. Fazeli

  2. Harvard Medical School, Boston, MA, USA

    A. T. Faje, M. A. Bredella, M. L. Bouxsein, A. Klibanski & P. K. Fazeli

  3. Department of Radiology, Massachusetts General Hospital, Boston, MA, USA

    M. A. Bredella

  4. Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, MA, USA

    M. L. Bouxsein

  5. Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA

    M. L. Bouxsein

  6. Neuroendocrinology Unit, Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    P. K. Fazeli

Authors
  1. T. Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. T. Faje
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Meenaghan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. A. Bredella
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. L. Bouxsein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Klibanski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. K. Fazeli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. K. Fazeli.

Ethics declarations

Competing interests

PKF is a consultant for Regeneron and Strongbridge Biopharma. Tran Dang, Alexander Faje, Erinne Meenaghan, Miriam Bredella, Mary Bouxsein and Anne Klibanski declare they have no conflict of interest.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dang, T., Faje, A.T., Meenaghan, E. et al. Bone marrow adipose tissue is associated with fracture history in anorexia nervosa. Osteoporos Int 33, 2619–2627 (2022). https://doi.org/10.1007/s00198-022-06527-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-022-06527-3

Keywords

Search

Navigation