One potential limitation of our osteoclast targeting platform remains that RANKL-RANK signaling is not entirely restricted to osteoclasts and their precursors, but is known to be involved in the regulation of other cell types. Studies have that RANKL-RANK signaling controls the development of lactating mammary glands in pregnancy, with the highest levels being at day 15.5 in mice (40, 41) . Several studies that looked at transgenic Rankl-/-and Rank-/-mice found that there was a complete absence of lymph nodes (42) . This led to further studies involving patients with an osteoclast-poor form of the autosomal recessive osteopetrosis (ARO), where they found the cause of the disease to be various mutations in RANKL (43) . The same research then found that these patients showed no palpable signs of lymph nodes, further strengthening the theory that RANKL-RANK signaling is involved in lymph node formation in humans. RANK is further known to be expressed by monocyte/macrophages and dendritic cells, specialized immune cells programmed to capture and process antigens in the body and present them to naïve T-cells (44) . However, the targeting of drug "cargo" to the RANK receptors of those cells may not necessarily result in drug action with those cells if the cargo is carefully chosen not to affect those cell types. For example, it is highly unlikely for any cell (other than the mature osteoclast) to express both the RANK receptor and calcitonin receptor at the same time. Thus, the Boolean "and/or" logic can be applied to the selection of the differential cargo targeting to cellular phenotypes expressing the RANK receptor at any given time. The extent of this limitation remains to be fully determined, however, should not necessarily preclude the further exploration of RANK receptor targeting strategies, which may in turn provide a more comprehensive understanding of RANK signaling and crosstalk with other signaling pathways.