Inter-organ communications in skeletal pathophysiology: from pathways to clinical therapies

Communications between organs contribute to propel physiological functions, as well as pathological processes. Growing evidence indicates that bone is continuously regulated by multiple layers of endocrine, immune, metabolic, and neural networks. The common bone diseases, including osteoporosis, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, are reported with tight associations to other nonbone organs. These organ-bone axes emphasize the interorgan communications that maintain the bone homeostasis and maintain individual health. In this review, we systematically summarize recent advances in the organ-bone communications, highlighting mechanistic innovations, such as the gut-bone-immune axis, neuro-immune-bone integration, hypothalamic-pituitary-adrenal axis, adipo-neuro-bone axis, and their connections with bone pathophysiology. Furthermore, we highlight circulating biomarkers and imaging advances reflecting organ-bone crosstalk. Finally, we discuss the clinical relevance, current research gaps, and unsolved questions of organ-bone communications in the diagnostic stratification, treatment selection, and multidisciplinary management of bone diseases.