Acromegalic osteoarthropathy: a new paradigm of pathological musculoskeletal remodeling.

Musculoskeletal disease is one of the major determinants of long-term morbidity in acromegaly, yet traditionally its pathophysiology and clinical management have been addressed through separate perspectives on skeletal fragility and arthropathy. Recent advances in skeletal biology, imaging, and biomechanics, as well as longitudinal clinical studies support a broader interpretation of acromegalic osteoarthropathy as a disorder of pathological musculoskeletal remodeling involving coordinated alterations of bone, joints, muscle, and body composition. In this review, we propose an integrative conceptual framework that brings together current evidence on the biological mechanisms underlying musculoskeletal remodeling, the clinical phenotype of active disease and the long-term consequences that frequently persist despite successful endocrine treatment. We discuss the strengths and limitations of currently available diagnostic approaches, including assessment of bone quality, vertebral fractures, arthropathy, and spinal biomechanics, and examine the clinical determinants of fracture risk beyond conventional bone mineral density evaluation. Particular emphasis is placed on the transition from endocrine-centered care to phenotype-driven management, highlighting current evidence regarding long-term surveillance, disease modification, and multidisciplinary management of persistent musculoskeletal disability. Collectively, the available evidence indicates that bone fragility, arthropathy, muscle dysfunction, and altered body composition should no longer be considered solely as isolated complications but may be interpreted as biologically related manifestations within a shared framework of pathological musculoskeletal remodeling. This integrated framework provides a biologically coherent interpretation of acromegalic osteoarthropathy and has important implications for individualized patient care, future translational research, and the development of disease-modifying therapeutic strategies aimed at preserving lifelong musculoskeletal health.