Potential Role of Odanacatib in the Treatment of Postmenopausal Intervertebral Disc Degeneration

Abstract

Odanacatib (ODN), a cathepsin K (CatK) inhibitor, is widely used for the treatment of postmenopausal osteoporosis. However, whether ODN is efficient in delaying intervertebral disc degeneration (IVDD) remaining unknown. We aimed to explore the effect of ODN in the postmenopausal IVDD using an ovariectomized (OVX) mouse model. We collected the disc tissues from female spinal fracture patients and analyzed the CatK expression in different estrogen levels. Besides, we injected ranged concentration of OND subcutaneously in the OVX mice and tested the disc height index (DHI), aggrecan positive area, collagen I, collagen II, inflammatory factors, and apoptosis-related gene expression comparing to control. The intervertebral disc degraded and the CatK gene expression decreased in the disc lacking of estrogen. OVX method increased the collagen I, MMP-3, MMP-13, caspase-3, and caspase-8 expression, but reduced DHI, and the content of aggrecan and collagen II, indicating an IVDD tendency. However, the ODN treatment could suppress MMP-3, MMP-13, caspase-3, and caspase-8 and protect the stability of extracellular matrix (ECM). ODN is a potential drug to delay the IVDD by suppressing apoptosis and ECM degradation.