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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Pituitary Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1414101

GH receptor polymorphisms guide second-line therapies to prevent acromegaly skeletal fragility: preliminary results of a pilot study

Provisionally accepted
Sabrina Chiloiro Sabrina Chiloiro 1,2*Flavia Costanza Flavia Costanza 1,2Antonella Giampietro Antonella Giampietro 1,2*Amato Infante Amato Infante 1,2*Pier Paolo Mattogno Pier Paolo Mattogno 1,2Flavia Angelini Flavia Angelini 1,2*Consolato Gullì Consolato Gullì 1,3*Liverana Lauretti Liverana Lauretti 1,2Mario Rigante Mario Rigante 1,2*Alessandro Olivi Alessandro Olivi 1,2Laura De Marinis Laura De Marinis 1,2Francesco Doglietto Francesco Doglietto 1,2*Antonio Bianchi Antonio Bianchi 1,2*Alfredo Pontecorvi Alfredo Pontecorvi 1,2
  • 1 Università Cattolica del Sacro Cuore, Rome, Italy
  • 2 Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy
  • 3 Agostino Gemelli University Policlinic, Rome, Lazio, Italy

The final, formatted version of the article will be published soon.

    Background: Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies.Methods. A longitudinal, retrospective, observational was conducted on a cohort study on 45 acromegalic patients not-responsive to first-generation somatostatin receptor ligands (fg-SRLs) and treated with GHR antagonist (Pegvisomant) or with the second-generation SRLs (Pasireotide longacting release).Results. Second line treatments were Pegvisomant plus fg-SRLs in 26 patients and Pasireotide LAR in 19 patients. From the group treated with fg-SRLs+Peg-V, the fl-GHR isoform was identified in 18 patients (69.2%) and the d3-GHR isoform in 8 patients (30.8%). I-VFs arose exclusively in fl-GHR isoform carriers (p=0.039). From the group treated with Pasireotide LAR, the fl-GHR isoform was identified in 11 patients (57.9%), and the d3-GHR isoform in 8 patients (42.1%). I-VFs arose exclusively in d3-GHR isoform carriers (p=0.018). Patients with fl-GHR isoform had a higher risk for i-VFs if treated with fg-SRL+Peg-V (OR: 1.6 95%IC: 1.1-2.3, p=0.04), and a lower risk if treated with Pasi-LAR (OR: 0.26 IC95%: 0.11-0.66, p=0.038).Conclusions. Our data support a predictive role of the GHR isoforms for the occurrence of i-VFs in acromegalic patients treated with second-line drugs, tailored to the individual patient. The knowledge of the GHR polymorphism may facilitate the choice of second-line therapies, improving the therapeutic approach, in the context of personalized medicine.

    Keywords: Fracture, osteopenia, Osteoporosis, Acromegaly, pegvisomant, somatostatin receptor ligands, pasireotide Abbreviations

    Received: 08 Apr 2024; Accepted: 07 Aug 2024.

    Copyright: © 2024 Chiloiro, Costanza, Giampietro, Infante, Mattogno, Angelini, Gullì, Lauretti, Rigante, Olivi, De Marinis, Doglietto, Bianchi and Pontecorvi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Sabrina Chiloiro, Università Cattolica del Sacro Cuore, Rome, Italy
    Antonella Giampietro, Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy
    Amato Infante, Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy
    Flavia Angelini, Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy
    Consolato Gullì, Agostino Gemelli University Policlinic, Rome, 00168, Lazio, Italy
    Mario Rigante, Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy
    Francesco Doglietto, Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy
    Antonio Bianchi, Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy

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