Mechanism Reversing Bone Resorption to Formation During Bone Remodeling

The mechanism reversing bone resorption to formation during the remodeling cycle has remained a black box for many years—but starts now to be understood. First, the use of specific cell activity markers in histological sections oriented along the axis of the remodeling cycles, allowed identifying the successive cell activities linking the onset of resorption and the onset of formation. A dense osteoclast population initiating resorption is followed by an alternation of osteoclasts and osteoprogenitors (i.e., reversal cells) lining the eroded surface. This cell arrangement thus reveals the existence of a mixed “reversal-resorption” phase allowing several waves of resorption and multiple interactions between osteoclasts and osteoprogenitors. Importantly, the density of osteoprogenitors continuously grows along the eroded surface until reaching a threshold density permissive for initiation of bone formation. Next, the analysis of proliferation and differentiation markers indicated that the cell layer forming a canopy over the remodeling site is the local source of osteoprogenitors for recruitment onto the eroded surface. Functional support for this view was provided by the fact that decreased canopy coverage is associated with less recruitment of osteoprogenitors on the eroded surface and lower activation frequency of bone formation, throughout a diversity of pathophysiological conditions.