Atorvastatin reduces zoledronic acid-induced osteonecrosis of the jaws of rats.

Abstract

The aim of this study was to evaluate the effect of Atorvastatin on Bisphosphonate-induced osteonecrosis of the jaws of rats. Wistar rats were divided into 4 groups: Saline, Zoledronic Acid, Atorvastatin before or after teeth extraction. BRONJ was induced by Zoledronic Acid (0.1 mg/kg). On day 42, animals were submitted to dental extraction. Atorvastatin was administered at 27 mg/kg for 3 weeks before or after oral procedure. Animals were euthanized on day 77. Maxillae were removed for macro and microscopic analyses. Immunohistochemistry for Dickopff (DKK) -1, Wnt 10b, β-catenin and caspase-3 was performed. Gingival TNF-α and IL-1β was evaluated and blood samples were collected for biochemical dosage. Atorvastatin improved mucosal healing, increased viable osteocytes (by 43 % and 47 % on pre- and post- Atorvastatin groups, respectively), while reduced Caspase-3 immunoexpression. ATV reduced bone sequestration and modulated inflammation, marked by reduction of gingival IL-1 and TNF. Atorvastatin improved the amount and quality of collagen, increased mineral content and reduced tissue solubility. When administrated prior to teeth extraction, Atorvastatin increased the number and activity of osteoblasts, through activation of the Wnt pathway. In summary, the anti-inflammatory and bone anabolic effects of Atorvastatin, maintained bone vitality, metabolism and structure, acting as an interesting pharmacological tool to modulate the disease or to assist BRONJ therapy. • Atorvastatin prevents bisphosphonate-induced osteocyte death. • Atorvastatin modulates inflammation and improves bone quality. • Atorvastatin reduces inflammation due to bisphosphonate-induced osteonecrosis. • Atorvastatin stimulates osteoblast proliferation via Wnt pathway. • Atorvastatin can be a useful tool to assist BRONJ therapy.