, Volume 53, Issue 3, pp 860–864 | Cite as

Epicardial fat is a negative predictor of spine volumetric bone mineral density and trabecular bone score in acromegaly

  • Elena ValassiEmail author
  • Iris Crespo
  • Jorge Malouf
  • David Vilades
  • Ruben Leta
  • Jaume Llauger
  • Eulàlia Urgell
  • Anna Aulinas
  • Ana Maria Marín
  • Betina Biagetti
  • Susan M. Webb
Research Letter


Growth hormone (GH) and insulin-like growth factor-I (IGF-I) excess in acromegaly (ACRO) are associated with abnormal bone remodeling and fat distribution [1]. GH and IGF-I play an important role in regulating body composition and modulating the interaction linking bone and fat. While GH is lipolytic and stimulates lipid oxidation [2], GH and IGF-I play an anabolic effect on bone, enhancing osteoblast differentiation and bone formation [3]. Thus, ACRO may be an interesting model to gain insight into the relationship between bone and fat, and its potential hormone determinants.

Patients with ACRO are at elevated risk of vertebral fractures [4], even in the presence of normal areal bone mineral density (aBMD), suggesting that exposure to GH/IGF-I excess may be associated with impaired bone microarchitecture [5]. ACRO is also characterized by a change in fat distribution, namely reductions of both subcutaneous (SAT) and visceral abdominal adipose tissue (VAT) [2]. Epicardial...


Acromegaly Epicardial fat Volumetric bone mineral density Trabecular bone score Dickkopf-related protein 1 (DKK1) 





Areal bone mineral density


C-terminal telopeptide of type 1 collagen


Areal bone mineral density


Dickkopf-related protein 1


Dual-energy X-ray absorptiometry


Epicardial adipose tissue


Free fatty acids


Growth hormone


Growth hormone deficiency


Insulin-like growth factor-I


Lumbar spine volumetric bone mineral density


Multidetector computed tomography


Recombinant growth hormone


Quantitative computed tomography


Subcutaneous adipose tissue


Trabecular bone score


Total procollagen type 1 amino-terminal propeptide


Visceral adipose tissue





We gratefully acknowledge Silvia Herrera-Bachs, Mª Rosa Sust Martínez, and Rosa Homs Serradesanferm for their technical support. We are indebted to all the subjects participating in this study.


This work was supported by the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (FIS PI 11-00001 y FIS PI 14-0194), and FEDER funds, and Fundación Salud 2000 (Merck Serono Grant 2012). E.V. is a recipient of a “Juan de la Cierva” postdoctoral grant from the Spanish Ministry of Economy and Competitiveness (MINECO).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    A. Colao, D. Ferone, P. Marzullo, G. Lombardi, Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr. Rev. 25, 102–152 (2005)CrossRefGoogle Scholar
  2. 2.
    P.U. Freda, W. Shen, S.B. Heymsfield, C.M. Reyes-Vidal, E.B. Geer, J.N. Bruce, D. Gallagher, Lower visceral and subcutaneous but higher intermuscular adipose tissue depots in patients with growth hormone and insulin-like growth factor I excess due to acromegaly. J. Clin. Endocrinol. Metab. 93, 2334–2343 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    A. Giustina, G. Mazziotti, E. Canalis, Growth hormone, insulin-like growth factors, and the skeleton. Endocr. Rev. 29, 535–559 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    G. Mazziotti, E. Biagioli, F. Maffezzoni, M. Spinello, V. Serra, R. Maroldi, I. Floriani, A. Giustina, Bone turnover, bone mineral density, and fracture risk in acromegaly. J. Clin. Endocrinol. Metab. 100, 384–394 (2015)CrossRefPubMedGoogle Scholar
  5. 5.
    M. Madeira, L.V. Neto, F. de Paula ParanhosNeto, I.C. Barbosa Lima, L.M. Carvalho de Mendonça, M.R. Gadelha, M.L. Fleiuss de Farias, Acromegaly has a negative influence on trabecular bone, but not on cortical bone, as assessed by high-resolution peripheral quantitative computed tomography. J. Clin. Endocrinol. Metab. 98, 1734–1741 (2013)CrossRefPubMedGoogle Scholar
  6. 6.
    G. Iacobellis, Epicardial adipose tissue in endocrine and metabolic diseases. Endocrine 46, 8–15 (2014)CrossRefPubMedGoogle Scholar
  7. 7.
    O. Topaloglu, M.S. Arslan, O. Turak, Z. Ginis, M. Sahin, M. Cebeci, B. Ucan, E. Cakir, B. Karbek, M. Ozbek, E. Cakal, T. Delibasi, Three different non-invasive methods in the evaluation of subclinical cardiovascular disease in patients with acromegaly: epicardial fat thickness, aortic stiffness and serum cell adhesion molecules. Clin. Endocrinol. 80, 726–734 (2014)CrossRefGoogle Scholar
  8. 8.
    V. Gilsanz, J. Chalfant, A.O. Mo, D.C. Lee, F.C. Dorey, S.D. Mittelman, Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J. Clin. Endocrinol. Metab. 94, 3387–3393 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    A.C. Ng, L.J. Melton III, E.J. Atkinson, S.J. Achenbach, M.F. Holets, J.M. Peterson, S. Khosla, M.T. Drake, Relationship of adiposity to bone volumetric density and microstructure in men and women across the adult lifespan. Bone 55, 119–125 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    B.C. Silva, W.D. Leslie, H. Resch, O. Lamy, O. Lesnyak, N. Binkley, E.V. McCloskey, J.A. Kanis, J.P. Bilezikian, Trabecular bone score: a non invasive analytical method based upon the DXA images. J. Bone Miner. Res. 29, 518–530 (2014)CrossRefPubMedGoogle Scholar
  11. 11.
    H.Z. Ke, W.G. Richards, X. Li, M.S. Ominsky, Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr. Rev. 33, 747–783 (2012)CrossRefPubMedGoogle Scholar
  12. 12.
    C. Christodoulides, M. Laudes, W.P. Cawthorn, S. Schinner, M. Soos, S. O’Rahilly, J.K. Sethi, A. Vidal-Puig, The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis. J. Cell Sci. 119(12), 2613–2620 (2006)CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    T. Ueland, N.C. Olarescu, A.P. Jorgensen, K. Otterdal, P. Aukrust, K. Godang, T. Lekva, J. Bollerslev, Increased serum and bone matrix levels of the secreted Wnt antagonist DKK-1 in patients with GH deficiency in response to GH treatment. J. Clin. Endocrinol. Metab. 100, 736–743 (2015)CrossRefPubMedGoogle Scholar
  14. 14.
    A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed, A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95, 3141–3148 (2010)CrossRefPubMedGoogle Scholar
  15. 15.
    T. Yoshizumi, T. Nakamura, M. Yamane, A.H. Islam, M. Menju, K. Yamasaki, T. Arai, K. Kotani, T. Funahashi, S. Yamashita, Y. Matsuzawa, Abdominal fat: standardized technique for measurement at CT. Radiology 211, 283–286 (1999)CrossRefPubMedGoogle Scholar
  16. 16.
    C. Battista, J. Chiosini, S. Muscarella, G. Guglielmi, M.L. Mascia, V. Carnevale, A. Scillitani, Spinal volumetric trabecular bone mass in acromegalic patients: a longitudinal study. Clin. Endocrinol. 70, 378–382 (2009)CrossRefGoogle Scholar
  17. 17.
    A.R. Hong, J.H. Kim, S.W. Kim, S.Y. Kim, C.S. Shin, Trabecular bone score as a skeletal fragility index in acromegalic patients. Osteoporos. Int. (2015) [Epub Ahead of print]Google Scholar
  18. 18.
    M. Russell, N. Mendes, K.K. Miller, C.J. Rosen, H. Lee, A. Klibanski, M. Misra, Visceral fat is a negative predictor of bone density measures in obese adolescent girls. J. Clin. Endocrinol. Metab. 95, 1247–1255 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    J.M. Marchington, C.M. Pond, Site-specific properties of pericardial and epicardial adipose tissue: the effects of insulin and high-fat feeding on lipogenesis and the incorporation of fatty acids in vitro. Int. J. Obes. 14, 1013–1022 (1990)PubMedGoogle Scholar
  20. 20.
    J.R. Chen, O.P. Lazarenko, X. Wu, Y. Tong, M.L. Blackburn, K. Shankar, T.M. Badger, M.J. Ronis, Obesity reduces bone density associated with activation of PPARγ and suppression of Wnt/β-catenin in rapidly growing male rats. PLoS One 5, e13704 (2015)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Elena Valassi
    • 1
    Email author
  • Iris Crespo
    • 1
  • Jorge Malouf
    • 2
  • David Vilades
    • 3
  • Ruben Leta
    • 3
  • Jaume Llauger
    • 4
  • Eulàlia Urgell
    • 5
  • Anna Aulinas
    • 1
  • Ana Maria Marín
    • 2
  • Betina Biagetti
    • 6
  • Susan M. Webb
    • 1
  1. 1.Endocrinology/Medicine Department, Research Center for Pituitary Diseases, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant PauISCIII and Universitat Autònoma de Barcelona (UAB)BarcelonaSpain
  2. 2.Mineral Metabolism Unit, Medicine DepartmentHospital Sant PauBarcelonaSpain
  3. 3.Cardiology DepartmentHospital Sant PauBarcelonaSpain
  4. 4.Radiology DepartmentHospital Sant PauBarcelonaSpain
  5. 5.Biochemistry DepartmentHospital Sant PauBarcelonaSpain
  6. 6.Endocrinology DepartmentHospital Vall d’HebronBarcelonaSpain

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