N-acetyl-L-cysteine Inhibits Wear Particle-Induced Prosthesis Loosening

Abstract

To study whether N-acetyl-L-cysteine (NAC) has beneficial effects on wear particle-induced osteoclastogenesis and osteolysis. In vitro, cells were cultured for 5 d and were then exposed to polymethylmethacrylate (PMMA) particles or were pretreated with NAC 1 h prior to stimulation with optimal PMMA particles. After 48 h, the number of osteoclasts was determined by tartrate-resistant acid phosphatase (TRAP) staining. In vivo, a murine calvarial model of PMMA particle-induced osteolysis, was used. PMMA particles were implanted on the calvariae of C57BL/J6 mice, and NAC (10 and 50 mg/kg) was given intraperitoneally every day. Two weeks later, the calvariae were removed and processed for micro-CT and histomorphometry analysis. TRAP staining showed that the osteoclastogenic response was dose-dependent with PMMA particles. Compared with the PBS group, the PMMA group showed a significant decrease in bone mineral density (BMD), bone volume fraction (BVF), cortical mean thickness (CMT), and cortical area/total area (Ct) (P< 0.05). Treatment with NAC (10 and 50 mg/kg) attenuated the PMMA particle-induced decrease in BMD, BVF, CMT, and Ct (P < 0.05 versus PMMA group). NAC inhibited the osteoclastogenesis and osteolysis that is caused by wear particles. The TRAP (+) osteoclast number and the osteolysis area in PBS, PMMA, NAC (10 mg/kg), and NAC (50 mg/kg) were 6.0 ± 0.6, 22.5 ± 1.2, 15.8 ± 0.7, 8.7 ± 1.0 and 0.075 ± 0.011, 0.340 ± 0.014, 0.231 ± 0.018, 0.142 ± 0.026 mm(2), respectively (P< 0.05). Our in vitro and in vivo work shows that NAC may effectively inhibit osteoclastogenesis and may suppress wear particle-induced osteolysis, indicating that NAC may be useful in the prevention or treatment of wear particle-induced prosthesis loosening.