Osteoclasts: more than ‘bone eaters’

•Osteoclasts modify the skeletal environment beyond their ability to resorb bone. •Bone-forming osteoblasts and their precursors are regulated by osteoclasts. •Cancer, hematopoietic, and immune cells are targets of osteoclast-derived factors. •Insight into the osteoclast may improve outcomes for patients with bone diseases. As the only cells definitively shown to degrade bone, osteoclasts are key mediators of skeletal diseases including osteoporosis. Bone-forming osteoblasts, and hematopoietic and immune system cells, each influence osteoclast formation and function, but the reciprocal impact of osteoclasts on these cells is less well appreciated. We highlight here the functions that osteoclasts perform beyond bone resorption. First, we consider how osteoclast signals may contribute to bone formation by osteoblasts and to the pathology of bone lesions such as fibrous dysplasia and giant cell tumors. Second, we review the interaction of osteoclasts with the hematopoietic system, including the stem cell niche and adaptive immune cells. Connections between osteoclasts and other cells in the bone microenvironment are discussed within a clinically relevant framework. As the only cells definitively shown to degrade bone, osteoclasts are key mediators of skeletal diseases including osteoporosis. Bone-forming osteoblasts, and hematopoietic and immune system cells, each influence osteoclast formation and function, but the reciprocal impact of osteoclasts on these cells is less well appreciated. We highlight here the functions that osteoclasts perform beyond bone resorption. First, we consider how osteoclast signals may contribute to bone formation by osteoblasts and to the pathology of bone lesions such as fibrous dysplasia and giant cell tumors. Second, we review the interaction of osteoclasts with the hematopoietic system, including the stem cell niche and adaptive immune cells. Connections between osteoclasts and other cells in the bone microenvironment are discussed within a clinically relevant framework.