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Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot single center experience

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Abstract

Introduction

Skeletal fragility is a clinically relevant and not-reversible complication of acromegaly, involving around 30–40% of patients since the disease diagnosis. Few studies have investigated the effects on skeletal health of medical therapies for acromegaly. In this retrospective longitudinal monocentre study, we investigated the outcome of skeletal fragility in patients treated with Pasireotide Lar in combination with Pegvisomant (Pasi-Lar + Peg-V), also comparing those observed in patients treated with conventional therapies.

Results

We included 6 patients treated with Pasi-Lar + Peg-V, 5 patients treated with Peg-V in monotherapy (m-Peg-V), 16 patients treated with Peg-V plus first-generation somatostatin receptor ligands (fg-SRLs + Peg-V), 9 patients treated with Pasi-Lar. None of the patients treated with Pasi-Lar + Peg-V experienced worsening of spine and femoral bone mineral density (BMD) and incident vertebral fractures (i-VFs). Eight patients experienced i-VFs. The frequency of i-VFs was significantly lower in patients treated with the Pasi-Lar + Peg-V (0/8; 0%), as compared to those observed in m-Peg-V treated patients (4/8; 50%, p = 0.02). The frequency of i-VFs was slightly but not significantly higher in Pasi-Lar treated patients (1/8; 12.5% p = 0.6) and in fg-SRLs + Peg-V treated patients (3/8; 37.5% p = 0.364), concerning those treated with Pasi-Lar + Peg-V (0/8; 0%). I-VFs occurred more frequently in patients with higher GH levels at acromegaly diagnosis (p < 0.001), and in patients who experienced a BMD worsening (p = 0.005).

Conclusion

Our preliminary data suggested that in conventional and multi-drug resistant acromegaly, the combination therapy Pasi-Lar + Peg-V may prevent the worsening of BMD and the occurrence of i-VFs. Prospective and translational studies should further validate these results and ascertain underlying physiopathology mechanisms.

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Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

The authors thank Prof Christine Hogan, native English speaker, for editing and reviewing the manuscript.

Funding

This study was supported by Università Cattolica del Sacro Cuore, Rome (Research line D1-2023).

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Author notes

  1. Francesco Doglietto and Antonio Bianchi contributed as coordinating author.

Authors and Affiliations

  1. Dipartimento di Medicina e Chirurgia traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy

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

  2. Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy

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

  3. Department of Diagnostic Imaging, Oncological Radiotherapy, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Amato Infante

  4. Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Pier Paolo Mattogno, Liverana Lauretti, Alessandro Olivi & Francesco Doglietto

  5. Department of Ageing, Neurosciences Head Neck, and Orthopedics Sciences, Catholic University of Sacred Heart, Rome, Italy

    Liverana Lauretti, Alessandro Olivi & Francesco Doglietto

Authors
  1. Sabrina Chiloiro
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  2. Antonella Giampietro
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  4. Pier Paolo Mattogno
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  6. Alessandro Olivi
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  7. Laura De Marinis
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  8. Alfredo Pontecorvi
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  9. Francesco Doglietto
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  10. Antonio Bianchi
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Contributions

SC and AI designed the study and draft the article. AG, PP, AI, and CD collected the data. LL, AP, AL, LDM, FD, and AB, drafted the article and revised it critically for important intellectual content. All authors approved the final version to be submitted.

Corresponding authors

Correspondence to Sabrina Chiloiro or Amato Infante.

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Conflict of interest

Declaration of competing interest SC, AB, AG, LDM has 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. All the authors declare that there are no conflict of interest that could be perceived as prejudicing the impartiality of this paper.

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Registry databases were approved by Institutional Review Board (ID:5367) and informed consent was waived for individual patients.

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Chiloiro, S., Giampietro, A., Infante, A. et al. Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot single center experience. Pituitary (2024). https://doi.org/10.1007/s11102-024-01398-9

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