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Prevalence of morphometric vertebral fractures in “difficult” patients with acromegaly with different biochemical outcomes after multimodal treatment

  • Clinical Management of Endocrine Diseases
  • Published:
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Abstract

Introduction

Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant.

Subjects and methods

Thirty-eight patients (25 females, 13 males) with acromegaly under Pegvisomant therapy were evaluated for vertebral fractures and bone mineral density at lumbar spine and femoral neck. Gonadal status, serum IGF1 levels and growth hormone receptor genotype were also assessed.

Results

Vertebral fractures were detected in 12 patients (31.6%). Fractured patients had longer duration of active disease (p = 0.01) with higher frequency of active acromegaly (p = 0.04), received higher dose of Pegvisomant (p = 0.008), and were more frequently hypogonadic (p = 0.02) as compared to patients who did not fracture. Stratifying the patients for gender, vertebral fractures were significantly associated with Pegvisomant dose (p = 0.02) and untreated hypogonadism (p = 0.02) in males and with activity of disease (p = 0.03), serum insulin-like growth factor-I values (p = 0.01) and d3GHR polymorphism (p = 0.005) in females. No significant association was found between vertebral fractures and bone mineral density at either skeletal site.

Conclusion

Vertebral fractures are a frequent complication of long-standing active acromegaly. When patients are treated with Pegvisomant, vertebral fractures may occur in close relationship with active acromegaly and coexistent untreated hypogonadism.

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References

  1. A. Giustina, G. Mazziotti, E. Canalis, Growth hormone, insuline-like growth factors, and the skeleton. Endocr. Rev. 29, 535–559 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. C. Bima, S. Chiloiro, M. Mormando, S. Piacentini, E. Bracaccia, A. Giampietro, L. Tartaglione, A. Bianchi, L. De Marinis, Understanding the effect of acromegaly on the human skeleton. J. Expert Rev. Endocrinol. Metab. 11, 263–270 (2015)

    Article  Google Scholar 

  3. G. Mazziotti, A. Bianchi, S. Bonadonna, V. Cimino, I. Patelli, A. Fusco, A. Pontecorvi, L. De Marinis, A. Giustina, Prevalence of vertebral fractures in men with acromegaly. J. Clin. Endocrinol. Metab. 93(12), 4649–4655 (2008)

    Article  CAS  PubMed  Google Scholar 

  4. G. Mazziotti, A. Bianchi, T. Porcelli, M. Mormando, F. Maffezzoni, A. Cristiano, A. Giampietro, L. De Marinis, A. Giustina, Vertebral fractures in patients with acromegaly: a 3-year prospective study. J. Clin. Endocrinol. Metab. 98, 3402–3410 (2013)

    Article  CAS  PubMed  Google Scholar 

  5. C. Battista, I. Chiodini, 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)

    Article  Google Scholar 

  6. M. Mormando, L.A. Nasto, A. Bianchi, G. Mazziotti, A. Giampietro, E. Pola, A. Pontecorvi, G. Giustina, L. De Marinis, GH receptor isoforms and skeletal fragility in acromegaly. Eur. J. Endocrinol. 171(2), 237–245 (2014)

    Article  CAS  PubMed  Google Scholar 

  7. K. Godang, N.C. Olarescu, J. Bollerslev, A. Heck, Treatment of acromegaly increases BMD but reduces Trabecular Bone Score – a longitudinal study. Eur. J. Endocrinol. 175(2), 155–164 (2016)

    Article  CAS  PubMed  Google Scholar 

  8. S. Grottoli, P. Maffei, F. Bogazzi, S. Cannavò, A. Colao, E. Ghigo, R. Gomez, E. Graziano, M. Monterubbianesi, P. Jonsson, L. De Marinis, ACROSTUDY: the Italian experience. Endocrine 48(1), 334–341 (2015). doi:10.1007/s12020-014-0393-9

    Article  CAS  PubMed  Google Scholar 

  9. A. Giustina Optimal use of pegvisomant in acromegaly: are we getting there?. Endocrine 48(1), 3–8 (2014) 10.1007/s12020-014-0462-0

    Article  PubMed  Google Scholar 

  10. A. Giustina, G. Arnaldi, F. Bogazzi, S. Cannavò, A. Colao, L. De Marinis, E. De Menis, E. Degli Uberti, F. Giorgino, S. Grottoli, A.G. Lania, P. Maffei, R. Pivonello, E. Ghigo, Pegvisomant in acromegaly: an update. J. Endocrinol. Invest. 40(6), 577–589 (2017). doi:10.1007/s40618-017-0614-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. S.E. Franck, A. Muhammad, A.J. van der Lely, S.J. Neggers, Combined treatment of somatostatin analogues with pegvisomant in acromegaly. Endocrine 52(2), 206–213 (2016). doi:10.1007/s12020-015-0810-8

    Article  CAS  PubMed  Google Scholar 

  12. G. Fairfield, L. Sesmilo, K. Katznelson, L. Katznelson, K. Pulaski, P.U. Freda, S. Stavrou, D. Kleinberg, A. Klibanski, Effects of a growth hormone receptor antagonist on bone markers in acromegaly. Clin. Endocrinol. 57, 385–390 (2002)

    Article  CAS  Google Scholar 

  13. C. Parkinson, M. Kassem, A. Heickendorff, A. Flyvbjerg, P.J. Trainer, Pegvisomant-induced serum insulin-like growth factor-i normalization in patients with acromegaly returns elevated markers of bone turnover to normal. J. Clin. Endocrinol. Metab. 88(12), 5650–5655 (2003)

    Article  CAS  PubMed  Google Scholar 

  14. C. Jimenez, M. Ayala-Ramirez, J. Liu, R. Nunez, R.F. Gagel, Inhibition of growth hormone receptor activation by pegvisomant may increase bone density in acromegaly. Horm. Metab. Res. 43, 55–61 (2011)

    Article  CAS  PubMed  Google Scholar 

  15. G. Mazziotti, E. Canalis, A. Giustina, Drug-induced osteoporosis: mechanisms and clinical implications. Am. J. Med. 123, 877–884 (2010)

    Article  CAS  PubMed  Google Scholar 

  16. A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed, Acromegaly Consensus Group. A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95, 3141–3148 (2010)

    Article  CAS  PubMed  Google Scholar 

  17. H.R. Boquete, P.G. Sobrado, H.L. Fideleff, A.M. Sequera, A.V. Giaccio, M.G. Suárez, G.F. Ruibal, M. Miras, Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis. J. Clin. Endocrinol. Metab. 88, 4702–4708 (2003)

    Article  CAS  PubMed  Google Scholar 

  18. J.F. Griffith, H.K. Genant, New advances in imaging osteoporosis and its complications. Endocrine 42, 39–51 (2012)

    Article  CAS  PubMed  Google Scholar 

  19. H.K. Genant, M. Jergas, L. Palermo, M. Nevitt, R.S. Valentin, D. Black, S.R. Cummings, Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The Study of Osteoporotic Fractures Research Group. J. Bone Mineral Res. 11, 984–996 (1996)

    Article  CAS  Google Scholar 

  20. G. Mazziotti, F. Maffezzoni, S. Frara, A. Giustina, Acromegalic osteopathy. Pituitary 20, 63–69 (2017)

    Article  CAS  PubMed  Google Scholar 

  21. G. Mazziotti, E. Biagioli, F. Maffezzoni, M. Spinelli, V. Serra, R. Maroldi, I. Floriani, A. Giustina, Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis. J. Clin. Endocrinol. Metab. 100(2), 384–394 (2015). doi:10.1210/jc.2014-2937

    Article  CAS  PubMed  Google Scholar 

  22. F. Mirza, E. Canalis, Secondary osteoporosis: pathophysiology and management. Eur. J. Endocrinol. 173(3), R131–R151 (2016)

    Article  Google Scholar 

  23. A. Bianchi, A. Giustina, V. Cimino, R. Pola, F. Angelini, A. Pontecorvi, L. De Marinis, Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J. Clin. Endocrinol. Metab. 94, 2015–2022 (2009)

    Article  CAS  PubMed  Google Scholar 

  24. A. Bianchi, G. Mazziotti, L. Tilaro, V. Cimino, F. Veltri, E. Gaetani, G. Pecorini, A. Pontecorvi, A. Giustina, L. De Marinis, Growth hormone receptor polymorphism and the effect of pegvisomant in acromegaly. Pituitary 12, 196–199 (2009)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research received specific grant from Pfizer.

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Authors and Affiliations

  1. Department of Endocrinology, Catholic University of the Sacred Heart, Rome, Italy

    S. Chiloiro, M. Mormando, A. Bianchi, A. Giampietro, D. Milardi, C. Bima, G. Grande, A. Pontecorvi & L. De Marinis

  2. Department of Molecolar and Translational Medicine, University of Brescia, Brescia, Italy

    A. M. Formenti

  3. Department of Medicine, Endocrine and Bone Unit, ASST Carlo Poma, Mantua, Italy

    G. Mazziotti

  4. Chair of Endocrinology, Vita-Salute San Raffaele University, Milan, Italy

    A. Giustina

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  1. S. Chiloiro
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  2. M. Mormando
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  3. A. Bianchi
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  4. A. Giampietro
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  5. D. Milardi
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  6. C. Bima
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  7. G. Grande
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  9. G. Mazziotti
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  10. A. Pontecorvi
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  11. A. Giustina
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  12. L. De Marinis
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Correspondence to L. De Marinis.

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The authors declare that they have no competing interests.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Chiloiro, S., Mormando, M., Bianchi, A. et al. Prevalence of morphometric vertebral fractures in “difficult” patients with acromegaly with different biochemical outcomes after multimodal treatment. Endocrine 59, 449–453 (2018). https://doi.org/10.1007/s12020-017-1391-5

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  • DOI: https://doi.org/10.1007/s12020-017-1391-5

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