ESPE Yearbook of Paediatric Endocrinology

Brief Summary:This review summarizes findings in mice on a new lineage of osteoclast-related cells that play a role in bone homeostasis at the resorption front. These ‘osteomorphs’ derive from fission of osteoclasts and are long-lived. They seem to interact with RANKL and may be involved in the rebound bone loss that is seen following denosumab (RANKL antagonist) therapy. The authors speculate on translational roles for osteomorphs in humans, including bone catabolic disorders such as osteoporosis, bone-targeted cancers and chronic inflammation.

Osteoclasts (OCL) are highly specialized multinucleated myeloid cells. OCL differentiate from myeloid stem cells to mononuclear OCL precursors which eventually fuse to multinucleated cells that resorb bone. After a life cycle of 2–3 weeks they were so far believed to undergo apoptosis. The life-cycle of OCL is regulated by an array of cytokines and hormones including PTH, RANKL, osteoprotegerin (OPG) and estrogens.

Several studies in mice recently described a new OCL-related cell type, ‘osteomorphs’. These result from fission of mature OCL and can subsequently again undergo fusion to generate multinucleated OCLs, in a novel cell re-cycling process. These studies provide mechanistic insight into the denosumab-withdrawal-rebound phenomenon as well as into other bone metabolic aspects informing about possible targets for interventions.

This review is written from a translational perspective. It summarises preclinical knowledge on osteomorphs in mice and translates this into possible implications in humans. However, osteomorphs have thus far been identified only in mice. Corresponding studies in humans are still lacking.

YES contributions by Dr. Simge Eren (14.17 and 14.18)