Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Abstract

Over the past few decades, significant progress has been made with respect to new concepts about the pathogenesis of osteoarthritis (OA). This article summarises some of the knowledge we have today on the involvement of the subchondral bone in OA. It provides substantial evidence that changes in the metabolism of the subchondral bone are an integral part of the OA disease process and that these alterations are not merely secondary manifestations, but are part of a more active component of the disease. Thus, a strong rationale exists for therapeutic approaches that target subchondral bone resorption and/or formation, and data evaluating the drugs targeting bone remodelling raise the hope that new treatment options for OA may become available.

Fig. 1

Interaction between the EphB4 receptor and ephrin B2 ligand leads to both a forward and a reverse signaling. The signal through the EphB4 receptor is considered a forward signal whereas the reverse signaling is through the ephrin B2 ligand. In OA subchondral bone osteoblasts, the activation of EphB4 receptor by ephrin B2 results in a decreased activation of PI3K/Akt which, in turn, inhibits some pro-inflammatory cytokines and matrix metalloproteinases as well as RANKL, all of which are involved in the remodeling process of the OA subchondral bone [81].