Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

Abstract

There is emerging awareness that subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). This review presents recent investigations on the cellular and molecular mechanism of subchondral bone remodeling, and summarizes the current interventions and potential therapeutic targets related to OA subchondral bone remodeling. The first part of this review covers key cells and molecular mediators involved in subchondral bone remodeling (osteoclasts, osteoblasts, osteocytes, bone extracellular matrix, vascularization, nerve innervation, and related signaling pathways). The second part of this review describes candidate treatments for OA subchondral bone remodeling, including the use of bone-acting reagents and the application of regenerative therapies. Currently available clinical OA therapies and known responses in subchondral bone remodeling are summarized as a basis for the investigation of potential therapeutic mediators.

18F–NaF simultaneous PET/MRI in osteoarthritis: Initial observations with case illustration

“…In a study, it was observed that the phenotype of subchondral trabecular bone beneath healthy cartilage was identical to that of severely injured cartilage, implying that subchondral bone changes in early OA could precede cartilage degradation. 9 Uptake of [18F] NaF indicates remodelling as well as bone metabolism, and is correlated with mineral apposition rate measured by bone histomorphometry. Early OA has been linked to alterations in remodelling of subchondral bone as well as vascularisation; as subchondral bone is metabolically active.…”

The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date

“… 88 , 89 Subchondral bone also undergoes remarkable alterations in both composition and structural organization, leading to adverse effects on the overlying articular cartilage. 90 Therefore, targeting the pathways that modify subchondral bone turnover is an attractive option for DMOAD research. 89 The pharmaceutical drugs in phase 2 and 3 stages of development for bone-driven endotype are summarized in Table 2 .…”

Update on Novel Non-Operative Treatment for Osteoarthritis: Current Status and Future Trends

“…In OA joints, subchondral bone undergoes remarkable remodeling processes in both composition and structure, including microarchitecture damage, bone marrow lesions, and bone cysts ( Hu et al, 2021 ). Subchondral bone remodeling is an adaptive change to local biomechanical and biological signals, which correspond to Wolff’s Law ( Zhu et al, 2020 ). When the bone is subjected to abnormal load-bearing, a number of bone properties change, including the increased bone mass, subchondral bone thickening, and trabecular restructuring ( Zhu et al, 2020 ).…”

“…Subchondral bone remodeling is an adaptive change to local biomechanical and biological signals, which correspond to Wolff’s Law ( Zhu et al, 2020 ). When the bone is subjected to abnormal load-bearing, a number of bone properties change, including the increased bone mass, subchondral bone thickening, and trabecular restructuring ( Zhu et al, 2020 ). These alterations are mediated by various types of cells, such as osteoblasts, osteoclasts, and osteocytes ( Sims and Martin, 2020 ).…”