e100 J Clin Endocrinol Metab, March 2020, 105(3):e100–e107 https://academic.oup.com/jcem doi:10.1210/clinem/dgz054 ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals. permissions@oup.com Received 25 June 2019. Accepted 25 September 2019. First Published Online 15 October 2019. CLINICAL RESEARCH ARTICLE Effects of Pegvisomant and Pasireotide LAR on Vertebral Fractures in Acromegaly Resistant to First-generation SRLs Sabrina Chiloiro, 1 Antonella Giampietro, 1 Stefano Frara, 2 Chiara Bima, 1 Federico Donfrancesco, 1 Cara Maya Fleseriu, 3,4 Alfredo Pontecorvi, 1 Andrea Giustina, 2 Maria Fleseriu, 4 Laura De Marinis, 1 and Antonio Bianchi 1 1 Pituitary Unit, Divisione di Endocrinologia, Fondazione Policlinico Universitario A. Gemelli IRCCS – Università Cattolica del Sacro Cuore, 00168, Rome, Italy; 2 Vita-Salute San Raffaele University, Milano, Italy; 3 University of Pittsburgh, Pittsburgh, PA, US; and 4 Oregon Health and Science University, Portland, OR, US ORCiD number: 0000-0001-9241-2392 (Sabrina Chiloiro). Purpose: Osteopathy is an emerging complication of acromegaly. In somatostatin receptor ligands (SRL)-resistant patients, pegvisomant (PegV) and pasireotide LAR (Pasi) are used for acromegaly treatment, but their effect on skeletal health is still not defined. Methods: In a longitudinal retrospective international study, we evaluated incidence of radiological vertebral fractures (VFs) in 55 patients with acromegaly resistant to first-generation SRL. Results: At study entry, prevalent VFs occurred in 23 patients (41.8%). Biochemical acromegaly control was reached in 66.7% of patients on PegV and in 66.7% of patients on Pasi. During the follow-up, incident VFs (iVFs) were detected in 16 patients (29.1%). Occurrence of iVFs was associated with prevalent VFs (P = .002), persistence of active acromegaly (P = .01) and higher value of insulin-like growth factor 1 (IGF-1) during follow-up (P = .03). Among patients with active disease at last visit, iVFs occurred less frequently in patients on treatment with Pasi (25%) compared to PegV (77.8% P = .04), independently of the IGF-1 values (P = .90). In patients who reached biochemical control, 22.7% on PegV and 12.5% on Pasi had iVFs (P = .40). Among both treatment groups, the presence of pre-existent VFs was the main determinant for iVFs. Conclusion: Our data show for the first time that patients with biochemically active disease treated with Pasi had lower risk of iVFs versus those treated with PegV. It also confirms that the presence of pre-existent VFs was the main determinant for iVFs. Additional studies on larger populations and with longer follow-up are needed to confirm our data and disclose the mechanisms underlying our findings. (J Clin Endocrinol Metab 105: e100–e107, 2020) O steopathy and bone fragility are emerging prob- lems in acromegaly (1–4). Until now, several cross-sectional (5–9) and prospective studies (10, 11) had consistently reported an high prevalence and incidence of vertebral fractures (VFs) in patients with acromegaly, in relationship with duration of active disease, co-existent untreated hypogonadism, and pre-existing VFs (12). Nowadays, medical therapy is an important option used either as adjuvant or primary medical treatment (13, 14). First-generation somatostatin receptor ligands (SRL) are used as first-line medical therapy of acromegaly in most cases, especially in Europe (13, 14) whereas pegvisomant (PegV) and pasireotide LAR (Pasi) are generally used as second-line therapy in patients partially controlled or un- controlled by first-generation SRLs (15, 16). A pleiotropic effects of both SRLs and PegV on systemic complications of acromegaly with potential Downloaded from https://academic.oup.com/jcem/article/105/3/e100/5588033 by guest on 26 February 2023