Pituitary hormones regulate skeletal physiology, and excess levels affect bone remodeling and alter bone microstructure. Vertebral fractures (VFs) are an early phenomenon of impaired bone health in secreting pituitary adenomas. However, they are not accurately predicted by areal bone mineral density (BMD). Emerging data demonstrate that a morphometric approach is essential for evaluating bone health in this clinical setting and is considered to be the gold standard method in acromegaly. Several novel tools have been proposed as alternative or additional methods for the prediction of fractures, particularly in pituitary-driven osteopa-thies. This review highlights the novel potential biomarkers and diagnostic methods for bone fragility, including their pathophysiological, clinical, radiologi-cal, and therapeutic implications in acromegaly, prolactinomas, and Cushing's disease.