Bone Health and Aging in Klinefelter Syndrome.

Klinefelter syndrome (KS) is typically diagnosed in young adults, but advances in prenatal testing have led to its recognition at a much earlier age. Conversely, diagnosis in late adulthood remains uncommon, but still occurs. Independently from the age at diagnosis, KS individuals now receive more accurate and tailored care management than in the past, thanks to advances in disease knowledge, improvements in health care systems, and greater awareness among both physicians and patients. Thus, individuals with KS are often placed under structured follow-up care, ensuring long-term monitoring that extends into older age. This review focuses on the pathophysiology and the management of osteopenia and osteoporosis in KS. Besides, aging with KS moves the physician's attention from reproductive function in the youth to comorbidities, cognitive changes and biological markers of aging and in the long run. From this perspective, chronic cardiovascular and metabolic diseases along with bone health become a priority in older individuals with KS. In particular, osteoporosis and osteoporotic fractures should be screened and treated with compensation of hypogonadism and eventual bone active therapy, since osteoporosis might be present already in young adults but worsens with advancing age. The extent to which these comorbidities, that are associated with KS in literature, occur more frequently in KS individuals (especially in older KS) compared to the general population remains to be established with certainty. In clinical practice, the management of older men with KS should include several assessments beyond hormone assays and hypogonadism treatment, aiming to address the health of individuals with KS in a holistic manner.