The effect of osteocyte‐derived RANKL on bone graft remodeling: An in vivo experimental study

Objectives Autologous bone is considered the gold standard for grafting, yet it suffers from a tendency to undergo resorption over time. While the exact mechanisms of this resorption remain elusive, osteocytes have been shown to play an important role in stimulating osteoclastic activity through their expression of receptor activator of NF‐κB (RANK) ligand (RANKL). The aim of this study was to assess the function of osteocyte‐derived RANKL in bone graft remodeling. Materials and Methods In Tnfsf11fl/fl;Dmp1‐Cre mice without osteocyte‐specific RANKL as well as in Dmp1‐Cre control mice, 2.6 mm calvarial bone disks were harvested and transplanted into mice with matching genetic backgrounds either subcutaneously or subperiosteally, creating 4 groups in total. Histology and micro‐computed tomography of the grafts and the donor regions were performed 28 days after grafting. Results Histology revealed marked resorption of subcutaneous control Dmp1‐Cre grafts and new bone formation around subperiosteal Dmp1‐Cre grafts. In contrast, Tnfsf11fl/fl;Dmp1‐Cre grafts showed effectively neither signs of bone resorption nor formation. Quantitative micro‐computed tomography revealed a significant difference in residual graft area between subcutaneous and subperiosteal Dmp1‐Cre grafts (p