3-D Structural Changes in Subchondral Bone and the Effect of Bisphosphonate Intervention in Early Osteoarthritis

Abstract

SUMMARY:This study aims to observe the 3-D structural changes in subchondral bone and the effects of bisphosphonate intervention in the early unsteady stage of the knee joint. Sixty healthy male New Zealand white rabbits were divided into the model group (n= 24), the bisphosphonate (Bis) group (n= 24), and the control group (n= 12). The rabbits' right knees were used to evaluate the structural changes. The Bis group received subcutaneous injections of bisphosphonate, while the model and control groups received subcutaneous injections of isotonic saline solution. After surgical preparation, the knee joint was dissected for Micro-CT examination, and the Micro-CT results were compared using ANOVA. In the fourth postoperative week, the bone volume fraction (BVF), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the model group were significantly lower than those of the control group (P<0.01). There was no significant difference between the Bis and control groups. In the twelfth postoperative week, BVF, Tb.Th, and Tb.N of the model group were significantly higher than those of the control and Bis groups (P <0.05). Similarly, bone mineral density was higher in the model group (P <0.01), while the trabecular spacing was significantly lower (P <0.05). In the early unsteady stage of the knee joint, the subchondral bone had markedly decreased, while obvious bone formation was visible in the late stage. Bisphosphonates could protect the subchondral bone structure by inhibiting bone absorption.

Bisphosphonates intake and its association with changes of periarticular bone area and three-dimensional shape: data from the Osteoarthritis Initiative (OAI)

“…Regarding the mechanisms by which bisphosphonates may have beneficial effects on OA progression, it has been suggested that these drugs might lead to local improvement in periarticular bone strength through reducing bone turnover, which would improve load absorbance; and therefore, reduce the biomechanical stress on the overlying cartilage and subsequently reduce cartilage breakdown 2,5 . This hypothesis has been primarily evaluated in a few clinical studies that showed a diminished periarticular trabecular bone loss in bisphosphonates users 13 .…”

“…It has been suggested that bisphosphonates may target the periarticular bone, which plays a pivotal role in the pathogenesis of OA and has been introduced as a biomarker of OA progression 4 . By inhibiting osteoclastic bone resorption and cellular secretion of transforming growth factor-b and matrix metalloproteinases, which are responsible for the cleavage of type II collagen; bisphosphonates may reduce periarticular bone turnover and lead to the local preservation of bone strength and microarchitecture, and eventually minimize OA progression 2,5 .…”