Acromegaly, a chronic condition characterized by growth hormone (GH) and, in turn, insulin-like growth factor-1 (IGF-I) excess, is burdened by a series of systemic and metabolic comorbidities that strongly impair quality of life (QoL) and life expectancy. Amongst them, a specific acromegalic osteopathy has been discovered, characterized by fragility fractures associated with high bone turnover, which need to be early detected, according to most recent guidelines, since they are very frequent and related to chronic pain and reduced QoL. Morphometric vertebral fractures (VFs) are an emerging landmark of skeletal fragility in general population as well as in clinical trials, and are highly prevalent in acromegaly, being reported to affect from 30 up to 60% of patients and represent an early and common event in disease history. Until now, same groups of patients with higher risk of vertebral fractures were identified, such as those carrying incident vertebral fractures, or affected by biochemical active acromegaly, concomitant hypogonadism, or diabetes mellitus. The main aim in the management of patients with acromegaly is to normalize IGF-I levels and restore acromegaly related symptoms. To aim this treatment objective, the first line of treatment of acromegaly, when feasible, is neurosurgery. In cases where surgical intervention fails to achieve biochemical control, medical therapy is recommended, with the objective of reaching normal levels of IGF-1 and GH age-corrected. Octreotide LAR and Lanreotide are the first-line medical therapy. In patients who have not achieved adequate control with standard doses of octreotide LAR and Lanreotide, increasing the dose and/or frequency of administration can lead to improved biochemical control. In patients who are unable to achieve control even with this approach, a switch to Pasireotide LAR may be considered. In instances where patients fail to achieve biochemical control with maximal doses of SRL, or in the presence of contraindications, the use of Pegvisomant as a second-line therapy may be considered. In addition, a combination of Pegvisomant and SRL represents a potential avenue for treating patients. Prevention of VFs in acromegaly remains an open issue. It has been shown that use of GH/IGF-I lowering treatments with first-generation SSA and Pegvisomant, may reduce the risk of VFs, while improving disease control. Moreover, in a retrospective and observational multicenter study, it was recently proved that patients treated with second generation SRLs (Pasireotide-LAR) developed less frequently VFs then patients treated with Pegvisomant.