Functional Heterogeneity Within Osteoclast Populations-a Critical Review of Four Key Publications that May Change the Paradigm of Osteoclasts.

Osteoclasts originate from the myeloid lineage and are best known for their unique ability to resorb bone. For decades, osteoclasts have been defined simply as multinucleated cells positive for tartrate-resistant acid phosphatase activity and quantified relative to the bone perimeter or surface in histomorphometric analyses. However, several recent, high-profile studies have demonstrated the existence of heterogeneous osteoclast populations, with variable origins and functions depending on the microenvironment. This includes long-term persisting osteoclasts, inflammatory osteoclasts, recycling osteoclasts (osteomorphs), and bone resorption modes. Most of these findings have been revealed through murine studies and have helped identify new targets for human studies. These studies have also uncovered distinct sets of behavioral patterns in heterogeneous osteoclast cultures. The underlying osteoclast heterogeneity likely drives differences in bone remodeling, altering patient risk for osteoporosis and fracture. Thus, identifying the underlying key features of osteoclast heterogeneity may help in better targeting bone diseases.