Novel approach to bone comorbidity in resistant acromegaly

Active acromegaly may lead to irreversible complications. Among them, acromegaly osteopathy and fragility (vertebral and hip) fractures have emerged as frequent and precocious events in the natural history of the disease, being correlated with longer disease duration and higher growth hormone (GH) levels, accounting for patients' reported poor quality of life, physical performance and other life-impacting complications. Differently from primary osteoporosis, bone mineral density is not a reliable tool to predict fracture risk in this clinical setting, as patients with active disease frequently have normal or slightly reduced bone mass; whereas bone quality is particularly compromised, as determined by low trabecular bone score (TBS) in patients with active disease as compared to healthy controls or patients with cured/controlled disease. The evidence of impaired bone microstructure has been profoundly investigated with different computed tomography (CT) techniques, reporting low trabecular number and thickness as well as wide but more porous cortical bone, providing an explanation for such a high prevalence of vertebral fractures (up to 40-50% in selected cohorts). Since data on bone-active drugs are scanty, disease control remains a cornerstone to prevent fractures. Nonetheless, some potential protective effects may derive from vitamin D supplementation and pasireotide therapies, independently from disease status. Aim of this manuscript is to review the current and emerging evidence on skeletal fragility in patients with active and resistant acromegaly.