Osteometabolic complications in patients with secreting pituitary adenomas: Is there an impact of gender?

Pituitary adenomas are common intracranial neoplasms and represent a clinically relevant but frequently underrecognized cause of secondary osteoporosis and fragility fractures. Hormonal excess, coexisting pituitary deficiencies, and the iatrogenic burden of multimodal treatments act synergistically to impair bone remodeling, microarchitecture, and mechanical strength. Consequently, skeletal fragility may manifest at a relatively young age and is often inadequately predicted by dual-energy X-ray absorptiometry (DXA)-derived areal bone mineral density (aBMD) alone.This narrative review summarizes current evidence on skeletal involvement in functioning pituitary adenomas, including acromegaly, Cushing's disease (CD), prolactinomas, and thyrotropin [TSH]-secreting adenomas (TSHomas), with a specific focus on sex-related differences relevant to clinical practice. Although several pituitary adenomas are more prevalent in women, male patients frequently present with delayed diagnoses, harboring larger and more aggressive tumors. Consequently, men may be affected by a longer cumulative exposure to hormone excess and a higher prevalence and severity of panhypopituitarism, often exacerbated by the mass effect and multiline therapies. Across clinical cohorts, these interacting factors are consistently associated with an increased burden of fragility fractures, particularly in male patients.In pituitary disorders, fracture risk is commonly underestimated because DXA-derived aBMD does not adequately capture alterations in bone quality and structural integrity. Comprehensive skeletal evaluation, including systematic vertebral morphometry, trabecular bone score (TBS), and selected advanced imaging techniques, improves detection of occult fractures and refines fracture risk stratification. Moreover, the persistently low awareness, diagnosis, and treatment rates of osteoporosis in men represent a substantial and potentially modifiable gap in care, particularly in secondary forms related to endocrine diseases.This review highlights the need for a proactive, sex-aware clinical approach that integrates endocrine management with appropriate skeletal assessment and bone-directed therapy, with the aim of reducing fracture burden and improving long-term outcomes in patients with pituitary diseases.