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Observational Study
. 2024 Aug 30:15:1414101.
doi: 10.3389/fendo.2024.1414101. eCollection 2024.

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

Sabrina Chiloiro  1   2 , Flavia Costanza  1   2 , Antonella Giampietro  1   2 , Amato Infante  3 , Pier Paolo Mattogno  4   5 , Flavia Angelini  1   2 , Consolato Gullì  3 , Liverana Lauretti  4   5 , Mario Rigante  6 , Alessandro Olivi  4   5 , Laura De Marinis  1   2 , Francesco Doglietto  4   5 , Antonio Bianchi #  1   2 , Alfredo Pontecorvi #  1   2
Affiliations
Observational Study

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

Sabrina Chiloiro et al. Front Endocrinol (Lausanne). .

Abstract

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 study was conducted on a cohort of 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 long-acting 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: GH receptor; acromegaly; fracture; osteopenia; osteoporosis; pasireotide; pegvisomant; somatostatin receptor ligands.

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Conflict of interest statement

SC, AB, AG, LDM have served as investigator for clinical trials funded by Novartis, Pfizer, Ipsen and Crinetics. SC and AB received grants from Pfizer. SC won the 2022 Arrigo Recordati Research Grant. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Clinical and molecular predictors of occurrence of incidental VFs in patients treated with Pasireotide Lar (A) and first generation SRLs + Pegvisomant (B). Forrest plot represents the odds ratio.
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References

    1. Giustina A, Mazziotti G, Canalis E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev. (2008) 5:535–59. doi: 10.1210/er.2007-0036 - DOI - PMC - PubMed
    1. Mazziotti G, Biagioli E, Maffezzoni F, Spinello M, Serra V, Maroldi R, et al. . Bone turnover, bone mineral density, and fracture risk in acromegaly: A meta-analysis. J Clin Endocrinol Metab. (2015) 2:384–94. doi: 10.1210/jc.2014-2937 - DOI - PubMed
    1. Giustina A. Acromegaly and vertebral fractures: facts and questions. Trends Endocrinol Metab. (2020) 4:274–5. doi: 10.1016/j.tem.2020.01.011 - DOI - PubMed
    1. Chiloiro S, Giampietro A, Gagliardi I, Bondanelli M, Veleno M, Ambrosio MR, et al. . Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience. Pituitary. (2022) 6:831–41. doi: 10.1007/s11102-022-01266-4 - DOI - PMC - PubMed
    1. Bima C, Chiloiro S, Mormando M, Piacentini S, Bracaccia E, Giampietro A, et al. . Understanding the effect of acromegaly on the human skeleton. Expert Rev Endocrinol Metab. (2016) 3:263–70. doi: 10.1080/17446651.2016.1179108 - DOI - PubMed

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