Fine and intricate tuning of the crosstalk between multiple organs is a fundamental process to maintain homeostasis and integrity in higher organisms including humans. Besides its classical roles such as structural support and mineral storage, bone is among the largest metabolic organs in the body with endocrine function and may be a key player in the multi-organ network.

Bone can communicate with other organs through various means. Direct contact with skeletal muscle, tendon and cartilage enables bone to exchange local cytokines, and even cellular components, and to share mechanical load. Bone contains the bone marrow tissue within, allowing for close communication with the hematopoietic and immune cells. Notably, osteoclasts originate from the hematopoietic stem cell and belong to the monocyte/macrophage lineage. On the other hand, osteoblasts originate from the mesenchymal lineage and share the same progenitors as adipocytes, myocytes, and chondrocytes. The regulation of the differentiation of mesenchymal progenitors into osteoblasts and adipocytes has been a key focus in investigating the reciprocal relationship between bone formation and fat accumulation.

Classical hormones targeting bone tissue include parathyroid hormone (PTH) and vitamin D. Accumulating evidence has revealed non-classical functions of these hormones beyond the regulation of bone and calcium metabolism. The pleiotropic effects of vitamin D have been extensively studied. Although very few studies have successfully demonstrated causal relationship between vitamin D status and non-skeletal biological processes, recent studies suggest the involvement of vitamin D in the regulation of glucose metabolism.

The bone itself is an endocrine organ secreting hormones such as FGF23 and osteocalcin. FGF23 plays a critical role in phosphate metabolism and is particularly important in clinical settings such as chronic kidney disease (CKD) and rickets/osteomalacia. It is now clear that every organ secretes various soluble factors and cytokines into the circulation that act on other distant organs. Although it may not be classical "hormones" by definition, many other organs also influence bone tissue via the systemic circulation. These organs include liver, kidneys, intestines, muscles, and more. In some cases, such organ–organ communication occurs through the neural network including the brain. Thus, bone and calciotropic hormones regulate the functions of other organs, which in turn affects bone metabolism and integrity.

Given such complex and bidirectional communications involving the bone tissue, it is no wonder that a wide variety of non-skeletal local diseases and metabolic abnormalities compromise bone strength and predispose patients to osteoporosis. In recent years, lifestyle diseases such as diabetes, chronic obstructive pulmonary disease (COPD) and CKD have attracted significant attention as secondary causes of osteoporosis posing an additional fracture risk.

In this special issue of the Journal of Bone and Mineral Metabolism, the authors discuss bone crosstalk with muscle, liver, lung, kidney, cartilage, and sensory and immune systems. This issue also covers the clinical aspects of bone abnormalities associated with COPD and CKD as well as the action of vitamin D on diabetes. We believe that these articles help readers from diverse fields understand multiple organ crosstalk involving bone. More effort should be made to elucidate roles of bone in regulating the functions of other organs through local, humoral, and neural communications in future studies.