Zoledronate alleviates subchondral bone collapse and articular cartilage degeneration in a rat model of rotator cuff tear arthropathy.

Abstract

To evaluate the humeral head bone volume of patients with cuff tear arthropathy (CTA) and examine the therapeutic effect of zoledronate in a rat modified model of CTA (mCTA). The bone mass in patients with CTA was measured using Hounsfield units from CT images. The mCTA was induced by transecting the rotator cuff, biceps brachii tendon, and superior half of the joint capsule in adult rat shoulders. A single subcutaneous injection of zoledronate was followed by bone histomorphometry and immunohistochemistry of the humeral head, as well as the Murine Shoulder Arthritis Score (MSAS) assessment. The humeral head bone volume was decreased in patients with CTA. In the mCTA model, M1 macrophages were increased in the synovium and were decreased by zoledronate treatment. The increased expressions of TNF-α, IL-1β and IL-6 in mCTA synovium and articular cartilage were suppressed in the zoledronate-treated mCTA group. The expression of catabolic enzymes in the articular cartilage and MSAS showed similar results. The zoledronate-treated mCTA group showed a decreased subchondral bone collapse with a decreased RANKL/OPG expression ratio and a suppressed number of osteoclasts compared with the control mCTA group. The enhanced expressions of HMGB1 and S100A9 in the mCTA shoulders were eliminated in the zoledronate-treated mCTA group. The humeral head subchondral bone was decreased in patients with CTA. In the mCTA model, the collapse and osteoarthritic changes were prevented by zoledronate administration. Zoledronate seemed to suppress the number of M1 macrophages in the synovium and osteoclasts in the subchondral bone.