ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP59 | DOI: 10.1530/endoabs.63.GP59

Effects of pegvisomant and pasireotide LAR on incidence of vertebral fractures in patients with acromegaly resistant to treatment with first-line somatostatin analogs

Sabrina Chiloiro1, Antonella Giampietro1, Antonio Bianchi1, Chiara Bima1, Stefano Frara2, Federica Mirra1, Federico Donfrancesco1, Cara Maria Fleseriu3,4, Maria Fleseriu4, Andrea Giustina2, De Marinis Laura1 & Alfredo Pontecorvi1

1OUS di Patologia Ipofisaria, UOC di Endocrinologia e Diabetologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS. Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Rome, Italy; 2Università Vita Salute San Raffaele, Milan, Italy; 3University of Pittsburgh, Pittsburgh, Pennsylvania, USA; 4Oregon Health and Science UniversityOregon Health and Science University, Portland, Oregon, USA.

Purpose: Osteopathy is an emerging complication of acromegaly characterized by increased bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures (VFs). In somatostatin analog (SSA)-resistant patients (pts), 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 international multicenter study, we evaluated incidence of radiological VFs in 55 pts (29F/26M), mean age 44.1 years (S.D.: 17) with acromegaly resistant to first line SSA.

Results: At the study entry, prevalent VFs (lumbar, thoracic) were identified in 23 pts (41.8%). Mean spine Z-score was −0.4 (−0.6 in PegV, −0.2 in Pasi group, respectively; P=0.49). Biochemical acromegaly control was reached in 22/31 pts on Peg-V (71%) and in 16/24 pts on Pasi (66.7%). During follow-up (mean 89.9 months for PegV group and 50.5 months for Pasi group), incident VFs (iVFs) were detected in 16 pts (29.1%). Occurrence of iVFs was associated with the presence of pre-existing VFs (P=0.009), persistence of active acromegaly (P=0.009) and higher median value of serum IGF-I during follow-up (P=0.04). There were no significant differences in age, gender, initial treatment choice and changes in lumbar spine BMD. iVFs occurred in 7/9 pts uncontrolled on Peg-V and 2/8 pts uncontrolled on Pasi. Among pts with active disease at last visit, iVFs occurred less frequently in pts on treatment with Pasi (25%) compared to Peg-V (77.8%), P=0.03, independently of the IGF-I values (P=0.9). In pts who reached acromegaly biochemical control, 5/17 (22.7%) on Peg-V and 2/14 (12.5%) pts on Pasi had iVFs, P=0.4. In pts on Peg-V, factors associated with iVFs during follow-up were persistence of active acromegaly and higher IGF-I values (median IGFxULN: 0.5 IQR:1.8 vs 2.6 IQR: 2.2 P=0.02). In pts treated with Pasi, we did not find any factors associated with iVFs. Furthermore, in pts with biochemically controlled acromegaly, no factor was associated with iVFs which occurred less frequently in pts treated with Pasi.

Conclusion: Our data confirm that active acromegaly is the main determinant of VFs and show for the first time that pts with biochemically active disease treated with Pasi had lower risk of incident VFs vs those treated with Peg-V. Conversely, no significant drug-related differences in iVFs in pts with controlled acromegaly were observed. Additional studies on larger populations and with longer follow-up are needed to confirm our data and disclose the mechanisms underlying our findings.