Abstract In the United States, 8.2 million women and 2.0 million men age 50 and above have osteoporosis. Moreover, half of all women and one quarter of men are projected to suffer an age-related low bone mass fracture within these populations. Importantly, an estimated 25% of individuals die within one year of a hip fracture. Cortical bone comprises the majority of skeletal bone mass (80%) and diminished cortical bone mass accounts for 70% of all bone lost with age. Although bone anabolic agents enhance vertebral cortical bone mass, efficacy of these agents is lower at the hip as compared to the spine (+12.3% spine, +3.9% hip); therefore, additional therapeutics improving cortical bone mass are desperately needed. Recent evidence shows that EMP-derived osteoclasts support balanced bone remodeling. In contrast, HSC-derived osteoclasts facilitate bone resorption in perturbed states. These observations suggest that osteoclasts of alternate developmental origins impact bone remodeling differentially, but we lack an understanding of how bone remodeling may differ within specific bone compartments (e.g., cortical versus trabecular bone). The two-year deliverables of the proposed study are: 1) identification of myeloid progenitors that aid in maintenance of cortical bone with age and 2) characterization of putative cells/molecules that promote coupling within cortical bone. If successful, this work could spur the development of new therapeutics that specifically limit age-associated cortical bone loss.