The Effect of RANKL/OPG Balance on Reducing Implant Complications

Abstract

Despite the phenomenal success of implants particularly in the realms of dentistry and orthopaedics, there are still challenges to overcome. The failure of implants resulting from infection, prosthetic loosening, and non-union continue to be the most notorious examples. The cascade of fracture healing and bone repair, especially with the presence of an implant, is complex because it involves a multifaceted immune response alongside the intricate process of bone formation and remodelling. Bone loss is a serious clinical problem that is frequently accompanied by chronic inflammation, illustrating that there is a convoluted relationship between inflammation and bone erosion. The effects of pro-inflammatory factors play a significant role in initiating and maintaining osteoclastogenesis that results in bone resorption by osteoclasts. This is because there is a disruption of the relative ratio between Receptor Activator of Nuclear Factor κB-Ligand (RANKL) and osteoprotegerin (OPG), which is central to modulating bone repair and remodelling. This review aims to provide a background to the bone remodelling process, the bone repair cascade post-implantation, and the associated complications. Furthermore, current clinical solutions that can influence bone formation via either internal or extrinsic mechanisms will be described. These efficacious treatments for osteolysis via targeting the RANKL/OPG ratio may be crucial to reducing the incidence of related implant failures in the future.

Keywords: OPG; RANKL; bone; bone loss; bone regeneration; complications; implants.

Figure 1

Mechanism of bone remodelling involving RANK/RANKL/OPG effects on osteoblasts and osteoclasts [11,19]. RANKL: Receptor Activator of Nuclear Factor κB-Ligand; OPG: osteoprotegerin; MSCs: mesenchymal stem or stromal cells; M-CSF: Macrophage Colony-Stimulating Factor; CFU-M: Colony Forming Unit-Macrophages.

Figure 2

The amassed adverse chronic effects of inflammatory cytokines and chemokines, which results in osteoclastogenesis and osteolysis that supersedes the negative feedback by OPG [1,11,19,21,28]. RANKL: Receptor Activator of Nuclear Factor κB-Ligand; OPG: osteoprotegerin; M-CSF: Macrophage Colony-Stimulating Factor; CFU-M: Colony Forming Unit–Macrophages; TNF-α: Tumour Necrosis Factor-α; IL-1: Interleukin-1; IL-6: Interleukin-6.