Growth hormone (GH) and insulin-like growth factor-I (IGF-I) have pleiotropic effects on the skeleton throughout the lifespan by influencing bone formation and resorption. Despite these positive effects on skeletal metabolism, in presence of GH and IGF-I excess, bone turnover increases excessively leading to deterioration of bone microarchitecture and high risk of fragility fractures, thereby impairing quality of life. Coexistent hypogonadism, diabetes mellitus, hypovitaminosis D, hyperparathyroidism, and over-replacement with glucocorticoids impair bone framework, however, the effects of acromegaly on bone mineral density (BMD) are still controversial and despite normalization of bone turnover after treatment, the risk for fractures remains increased. As a matter of fact, a major clinical aspect emerging from the studies published so far is the lack of clinical-diagnostic tools able to reliably predict the appearance of fractures in patients with acromegaly occurring even in the presence of normal or low-normal BMD. New radiological software and clinical devices have been employed in acromegaly patients highlighting a significant impairment of both cortical and cancellous bone. In this article, we summarize the pathophysiology, clinical aspects and the new diagnostic tools to better understand bone impairment in acromegaly.