Progression of vertebral fractures in patients with adrenocortical carcinoma undergoing mitotane therapy

Context: patients with adrenocortical carcinoma (ACC) are frequently on mitotane therapy for a long-time period. The drug exerts an adrenolytic activity requiring glucocorticoid supplementation, which can be potentially detrimental for bone. Objectives: to explore whether mitotane plus/minus chemotherapy is associated with an increased proportion of morphometric vertebral fractures (VFs) in ACC patients. Secondary objectives were: proportion of patients with VF progression, or worsening of the spinal deformity index (SDI) during mitotane therapy; predictive factors of VF progression and prognostic role of VF progression. Design and setting: multicenter, retrospective cohort study of patients with ACC who received mitotane alone or in association to chemotherapy, recruited from January 2010 to January 2020 in two reference centers in Italy and France. Results: a significant increase in the frequency of VFs before and after mitotane therapy was seen both in Italian (28.3% vs 47.8%, p: 0.04) and French (17.8% vs 35.6%, p 0.04) series. VF progression was observed in 39.1%, and 28.9% of patients, respectively. Baseline VFs and increased patient body mass index, but not the dose of cortisol supplementation, showed an independent association with VF progression at multivariate analysis. Among the 72 advanced ACC patients, progression of VFs was associated with a poorer survival. Conclusions: the administration of mitotane plus/minus chemotherapy in ACC patients impairs bone health independently from cortisol supplementation. Appropriate preventive measures to decrease the fracture risk should be implemented in these patients.