Endocrine Abstracts

Introduction: Skeletal fragility is a 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. We aim to investigate the frequency of incident vertebral fractures (i-VFs) in patients treated with Pasireotide Lar + Pegvisomant (study group), after at least 24 consecutive treatment months and to compare the i-VFs frequency in the study group with controls: patients treated with Pasireotide Lar, Pegvisomant in monotherapy (m-Peg-V), and in association to first-generation somatostatin receptor ligands (fg-SRLs+Peg-V).

Subjects and methods: A retrospective, longitudinal, observational was designed. For the study cohort, inclusion criteria were: (1) ascertained diagnosis of acromegaly; (2) age older than eighteen years; (3) not-controlled acromegaly during treatment for at least 12 consecutive months with fg-SRLs and further 12 consecutive months of treatment with Pasireotide Lar or Pegvisomant in monotherapy or in combination with fg-SRLs; (6) treatment with Pasi-Lar+Peg-V for at least 24 consecutive months. For the control groups, inclusion criteria were: (1) ascertained diagnosis of acromegaly; (2) age older than 18 years; (3) not-controlled acromegaly during treatment for at least 12 consecutive months with fg-SRLs; (4) controlled acromegaly after at least twelve consecutive months with Pasi-Lar or Pegvisomant in monotherapy or in combination with fg-SRLs. The exclusion criteria (both for the study cohort and for the control groups) were: (1) diagnosis of active neoplasia; (2) previous or current treatment with drugs known to cause fragility fractures, except for glucocorticoid replacement therapy for central adrenal insufficiency; (3) history of spine surgery or trauma.

Results: Six patients were treated with Pasi-Lar+Peg-V, 6 patients with Peg-V in monotherapy (m-Peg-V), 16 patients with fg-SRLs+Peg-V and 10 patients with Pasi-Lar. Eight patients experienced i-VFs. None Pasi-Lar+Peg-V treated patient experienced i-VFs. The i-VFs frequency was lower in Pasi-Lar+Peg-V treated patients (0/8; 0%), as compared to those observed in m-Peg-V treated patients (4/8; 50%, P=0.03). The i-VFs frequency was slightly higher in Pasi-Lar treated patients (1/8; 12.5% P=0.062) 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=0.04), 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 i-VFs occurrence. Prospective studies should further validate these results and ascertain underlying physiopathology mechanisms.