Management of medication-related osteonecrosis of jaw: Comparison between icariin and teriparatide in a rat model.

Abstract

The aim of this study is to compare the effects of icariin and teriparatide on the treatment of medication-related osteonecrosis of the jaw (MRONJ) using a rat model. Fifty rats undergoing ovariectomy were randomly assigned to control group (n=10) and the MRONJ model group (n=40). Zoledronic acid (0.2mg/kg) and dexamethasone (2mg/kg) were injected into rats in the model group for 8weeks while saline was applied in control group, then all rats underwent tooth extraction and bone defect. Eightweeks later, rats diagnosed with MRONJ (n=33) were randomly distributed to icariin (n=11), teriparatide (n=11), and the untreated (n=11) group, and rats received daily 150mg/kg icariin, 20µg/kg teriparatide, and no intervention, respectively, for 8weeks. Then, mandibulars were dissected for later examination. Rats diagnosed with MRONJ (33/40) demonstrated significantly larger area of soft tissue wound and necrotic bone with higher ratio of empty bone lacuna. Area of soft tissue wound and ratio of empty bone lacuna were significantly decreased in the icariin group compared with the untreated group, while teriparatide group revealed significantly higher ratio of receptor activator of NF-kB ligand (RANKL)-positive osteocytes, smaller area of necrotic bone and lower ratio of empty lacuna. The two agents were related to higher expression of BMP-2 in osteocytes but were not statistically significant. Icariin benefits MRONJ in terms of the area of soft tissue wound and ratio of empty lacuna. Teriparatide activates expression of RANKL and reduces the area of bone necrosis and ratio of empty lacuna in a MRONJ lesion. The data suggest possible healing improvement in patients with MRONJ and further studies to prove the efficacy of icariin.