SUN-LB075 Effects of Pegvisomant and Pasireotide LAR on Incidence of Vertebral Fractures in Patients with Acromegaly Resistant to Treatment with First-Line Somatostatin Analogs

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 yrs (SD: 17) with acromegaly resistant to first line SSA. Results: At the study entry, prevalent VFs (lumbar, thoracic) were identified in 23 pts (41.8%): 42 mild and 3 moderate (Genant score) VF. 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 the follow-up (mean 89.9 months for PegV group and 50.5 months for Pasi group), incident VFs were detected in 16 pts (29.1%). Occurrence of incident VFs was associated with the presence of pre-existing VFs (p=0.009), persistence of active acromegaly (p=0.009) and with 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. Incident VFs occurred in 7/9 pts not contolled on Peg-V and 2/8 pts not controlled on Pasi. Among pts with active disease at last visit, incident VFs 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 incident VFs, p=0.4. In pts on Peg-V, factors associated with incident VFs during follow-up were persistence of active acromegaly and higher values of IGF-I (median IGF x ULN: 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 incident VFs. Furthermore, in pts with biochemically controlled acromegaly, no factor was associated with incident VFs 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 incident VFs 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. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.