**4.5 Immune dysfunction**

Antiresorptive drugs together with other immunosuppressants such as corticosteroids, chemotherapy or methotrexate increases the possibility of osteonecrosis [3]. Ruggiero et al. [3] stated that in the beginning of investigating the influence of bisphosphonates on wound healing in animal models, to induce osteonecrosis, steroids were combined with bisphosphonates. Inflammation, delayed healing, mucosal ulceration, exposed bone, fistula and histologic necrosis are well documented symptoms in different animal species and in humans exposed to surgical procedures after application chemotherapy with antiresorptive drugs. Methotrexat is standard or first line drug for therapy of rheumatoid arthritis. It can be an iatrogenic cause of lymphoproliferative disorders in immunodeficient or immunosuppressed patients, resulting with osteonecrosis of the jaw in some cases [35].
