GH acts on various tissues and organs, like liver, kidney, bone and muscle. There are no conclusive data on adult onset GH deficiency (GHD) effects on bone remodeling. In fact reduced, increased or unchanged values of serum markers of bone formation and resorption have been described. However, a direct link between GHD and reduced bone mass in hypopituitarism is supported by reports that GH replacement therapy can improve bone mineral density (BMD) in these patients. Recently, many studies have shown an increased prevalence of osteoporosis in adult-onset GHD patients, and the fracture rate in these subjects seems to be twice that in the non-GH-deficient population. Long-term studies in these years have described a BMD increase in GHD patients during treatment with GH alone or in combination with biphosphonates. To understand if these BMD changes may result in a reduction of fracture risk, it is necessary to carry out a longitudinal follow-up of large cohorts of GHD adults on GH replacement therapy.