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Effects of pegvisomant and somatostatin receptor ligands on incidence of vertebral fractures in patients with acromegaly

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An Author Correction to this article was published on 23 February 2018

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Abstract

Purpose

Acromegalic osteopathy is an emerging complication of acromegaly characterized by increase in bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures (VFs). Somatostatin receptor ligands (SRLs) and pegvisomant (PegV) are used for treatment of acromegaly and there is evidence that both drugs may exert direct effects on peripheral targets regardless of biochemical control of disease. However, whether or not SRLs and PegV may directly influence skeletal health its is unknown.

Methods

In this longitudinal study, we evaluated the incidence of radiological VFs in 83 patients (48 females, 35 males; median age 47 years, range 18–80 years) who were treated with SRLs alone (42 cases), PegV alone (6 cases) or in combination with SRLs (35 cases) for median period of 82 months (range 36–126). PegV was given when acromegaly was not controlled by SRLs alone.

Results

During the follow-up, 29 patients (34.9%) developed incident VFs. In patients receiving PegV due to active disease during SRL therapy, incidence of VFs decreased significantly from 43.9 to 26.8% (p = 0.039). When acromegaly was controlled by PegV, the incidence of VFs was slightly but not significantly lower as compared to that observed in patients with biochemical control of disease by SRLs (10.0 vs. 26.7%; p = 0.09). In the multivariate logistic regression analysis, incident VFs were independently predicted by pre-existing VFs (odds ratio 61.0; p = 0.009), duration of active acromegaly (odds ratio 1.01; p = 0.05) and mean serum IGF-I during the follow-up (odds ratio 5.26; p = 0.03), regardless of the therapeutic regimen (odds ratio 1.05; p = 0.94).

Conclusions

PegV and SRLs had comparable effects on VF risk in acromegaly. The activity of disease was the main determinant of VFs independently of the drug used to control acromegaly.

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Change history

  • 23 February 2018

    The original version of the article contained an error in the results section of the Abstract. The vertebral fractures (VFs) odds ratio is incorrectly published as 61.0 and the correct value is 6.10.

References

  1. Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29(5):535–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Madeira M, Neto LV, de Paula Paranhos Neto F, Barbosa Lima IC, Carvalho de Mendonça LM, Gadelha MR, Fleiuss de Farias ML (2013) 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(4):1734–1741

    Article  CAS  PubMed  Google Scholar 

  4. Maffezzoni F, Maddalo M, Frara S, Mezzone M, Zorza I, Baruffaldi F, Doglietto F, Mazziotti G, Maroldi R, Giustina A (2016) Cone beam tomography analysis of bone microarchitecture in patients with acromegaly and vertebral fractures. Endocrine 54(2):532–542

    Article  CAS  PubMed  Google Scholar 

  5. Bonadonna S, Mazziotti G, Nuzzo M, Bianchi A, Fusco A, De Marinis L, Giustina A (2005) Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J Bone Miner Res 20(10):1837–1844

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Wassenaar MJ, Biermasz NR, Hamdy NA, Zillikens MC, van Meurs JB, Rivadeneira F, Hofman A, Uitterlinden AG, Stokkel MP, Roelfsema F, Kloppenburg M, Kroon HM, Romijn JA, Pereira AM (2011) High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly. Eur J Endocrinol 164(4):475–483

    Article  CAS  PubMed  Google Scholar 

  8. Brzana J, Yedinak CG, Hameed N, Fleseriu M (2014) FRAX score in acromegaly: does it tell the whole story? Clin Endocrinol 80(4):614–616

    Article  Google Scholar 

  9. Mazziotti G, Bianchi A, Porcelli T, Mormando M, Maffezzoni F, Cristiano A, Giampietro A, De Marinis L, Giustina A (2013) Vertebral fractures in patients with acromegaly: a 3-year prospective study. J Clin Endocrinol Metab 98(8):3402–3410

    Article  CAS  PubMed  Google Scholar 

  10. Claessen KM, Kroon HM, Pereira AM, Appelman-Dijkstra NM, Verstegen MJ, Kloppenburg M, Hamdy NA, Biermasz NR (2013) Progression of vertebral fractures despite long-term biochemical control of acromegaly: a prospective follow-up study. J Clin Endocrinol Metab 98(12):4808–4815

    Article  CAS  PubMed  Google Scholar 

  11. Mazziotti G, Chiavistelli S, Giustina A (2015) Pituitary diseases and bone. Endocrinol Metab Clin North Am 44(1):171–180

    Article  PubMed  Google Scholar 

  12. Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A, van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KKY, Casanueva FF, Melmed S (2014) A consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10(4):243–248

    Article  CAS  PubMed  Google Scholar 

  13. Giustina A, Arnaldi G, Bogazzi F, Cannavò S, Colao A, De Marinis L, De Menis E, Degli Uberti E, Giorgino F, Grottoli S, Lania AG, Maffei P, Pivonello R, Ghigo E (2017) Pegvisomant in acromegaly: an update. J Endocrinol Invest 40(6):577–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gola M, Bonadonna S, Mazziotti G, Amato G, Giustina A (2006) Resistance to somatostatin analogs in acromegaly: an evolving concept? J Endocrinol Invest 29(1):86–93

    Article  CAS  PubMed  Google Scholar 

  15. De Marinis L, Bianchi A, Mazziotti G, Mettimano M, Milardi D, Fusco A, Cimino V, Maira G, Pontecorvi A, Giustina A (2008) The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly. Pituitary 11(1):13–20

    Article  CAS  PubMed  Google Scholar 

  16. Giustina A, Gola M, Colao A, De Marinis L, Losa M, Sicolo N, Ghigo E (2008) The management of the patient with acromegaly and headache: a still open clinical challenge. J Endocrinol Invest 31(10):919–924

    Article  CAS  PubMed  Google Scholar 

  17. Neggers SJ, van Aken MO, de Herder WW, Feelders RA, Janssen JA, Badia X, Webb SM, van der Lely AJ (2008) Quality of life in acromegalic patients during long-term somatostatin analog treatment with and without pegvisomant. J Clin Endocrinol Metab 93(10):3853–3859

    Article  CAS  PubMed  Google Scholar 

  18. Mazziotti G, Giustina A (2010) Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review. Pituitary 13(1):60–67

    Article  CAS  PubMed  Google Scholar 

  19. Giustina A, Mazziotti G, Torri V, Spinello M, Floriani I, Melmed S (2012) Meta-analysis on the effects of octreotide on tumor mass in acromegaly. PLoS ONE 7(5):e36411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mazziotti G, Canalis E, Giustina A (2010) Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med 123(10):877–884

    Article  CAS  PubMed  Google Scholar 

  21. Chiloiro S, Mormando M, Bianchi A, Giampietro A, Milardi D, Bima C, Grande G, Formenti AM, Mazziotti G, Pontecorvi A, Giustina A, De Marinis L (2017) Prevalence of morphometric vertebral fractures in “difficult” patients with acromegaly with different biochemical outcomes after multimodal treatment. Endocrine. https://doi.org/10.1007/s12020-017-1391-5

    Google Scholar 

  22. Giustina A, Barkan A, Chanson P, Grossman A, Hoffman A, Ghigo E, Casanueva F, Colao A, Lamberts S, Sheppard M, Melmed S, Pituitary Society, European Neuroendocrine Association (2008) Guidelines for the treatment of growth hormone excess and growth hormone deficiency in adults. J Endocrinol Invest 31(9):820–838

    Article  CAS  PubMed  Google Scholar 

  23. Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S (2010) Acromegaly Consensus Group. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 95(7):3141–3148

    Article  CAS  PubMed  Google Scholar 

  24. Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) 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 Miner Res 11(7):984–996

    Article  CAS  PubMed  Google Scholar 

  25. Frara S, Maffezzoni F, Mazziotti G, Giustina A (2016) The modern criteria for medical management of acromegaly. Prog Mol Biol Transl Sci 138:63–83

    Article  CAS  PubMed  Google Scholar 

  26. Mazziotti G, Maffezzoni F, Frara S, Giustina A (2017) Acromegalic osteopathy. Pituitary 20(1):63–69

    Article  CAS  PubMed  Google Scholar 

  27. Godang K, Olarescu NC, Bollerslev J, Heck A (2016) Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study. Eur J Endocrinol 175(2):155–164

    Article  CAS  PubMed  Google Scholar 

  28. Bianchi A, Valentini F, Iuorio R, Poggi M, Baldelli R, Passeri M, Giampietro A, Tartaglione L, Chiloiro S, Appetecchia M, Gargiulo P, Fabbri A, Toscano V, Pontecorvi A, De Marinis L (2013) Long-term treatment of somatostatin analog-refractory growth hormone-secreting pituitary tumors with pegvisomant alone or combined with long-acting somatostatin analogs: a retrospective analysis of clinical practice and outcomes. J Exp Clin Cancer Res 32:40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Franck SE, Muhammad A, van der Lely AJ, Neggers SJ (2016) Combined treatment of somatostatin analogues with pegvisomant in acromegaly. Endocrine 52(2):206–213

    Article  CAS  PubMed  Google Scholar 

  30. Giustina A (2015) Optimal use of pegvisomant in acromegaly: are we getting there? Endocrine 48(1):3–8

    Article  CAS  PubMed  Google Scholar 

  31. Johansson H, Odén A, McCloskey EV, Kanis JA (2014) Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures. Osteoporos Int 25(1):235–241

    Article  CAS  PubMed  Google Scholar 

  32. Mazziotti G, Doga M, Frara S, Maffezzoni F, Porcelli T, Cerri L, Maroldi R, Giustina A (2016) Incidence of morphometric vertebral fractures in adult patients with growth hormone deficiency. Endocrine 52(1):103–110

    Article  CAS  PubMed  Google Scholar 

  33. Mazziotti G, Formenti AM, Adler RA, Bilezikian JP, Grossman A, Sbardella E, Minisola S, Giustina A (2016) Glucocorticoid-induced osteoporosis: pathophysiological role of GH/IGF-I and PTH/VITAMIN D axes, treatment options and guidelines. Endocrine 54(3):603–611

    Article  CAS  PubMed  Google Scholar 

  34. Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, Strasburger CJ, Wass JA, Giustina A (2013) A consensus on the diagnosis and treatment of acromegaly complications. Pituitary 16(3):294–302

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Pituitary Unit, Catholic University of the Sacred Heart, Rome, Italy

    Sabrina Chiloiro, Antonella Giampietro, Antonio Bianchi, Marilda Mormando, Alfredo Pontecorvi & Laura De Marinis

  2. Endocrine Unit, ASST Carlo Poma, Mantua, Italy

    Gherardo Mazziotti

  3. Vita-Salute San Raffaele University, Milan, Italy

    Stefano Frara & Andrea Giustina

Authors
  1. Sabrina Chiloiro
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  2. Gherardo Mazziotti
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  3. Antonella Giampietro
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  4. Antonio Bianchi
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  5. Stefano Frara
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  8. Andrea Giustina
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  9. Laura De Marinis
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Correspondence to Laura De Marinis.

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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. For this type of study formal consent is not required.

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Chiloiro, S., Mazziotti, G., Giampietro, A. et al. Effects of pegvisomant and somatostatin receptor ligands on incidence of vertebral fractures in patients with acromegaly. Pituitary 21, 302–308 (2018). https://doi.org/10.1007/s11102-018-0873-7

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