Skeletal mass is regulated by two key activities: bone removal (resorption) by hematopoietic lineage osteoclasts and bone matrix formation by mesenchymal lineage osteoblasts. During adult life, these activities occur sequentially on the same surface: a process termed as remodeling. Tiny packets of bone are removed by osteoclasts and replaced by new bone matrix produced by osteoblasts. This continual renewal process allows repair of mechanical imperfections and calcium homeostasis.

The group of cells responsible for remodeling is termed as the basic multicellular unit (BMU)(1). To maintain bone mass at the same level during adulthood, the bone formed in each BMU must replace precisely the amount removed by resorption within that BMU. This stimulation of osteoblast activity in response to resorption is termed “coupling”(2), and it has long been of interest to understand how these two distinct cell types, on the same bone surface but at different times, could be linked so their activities are equal. The BMU and coupling concepts originally included only osteoclasts and osteoblasts, but over recent years, as more cellular contributors to remodeling have been identified (such as T-cells, macrophages, osteocytes, and precursor populations of osteoblasts and osteoclasts), the number of cells in the BMU has expanded (3–5). So too, more signaling pathways within the BMU have been identified (6, 7). All these signals converge on two cell types: the osteoclast and osteoblast, for only those cells are able of bone resorption and bone formation, respectively.