**4.4 Soft tissue toxicity**

One of theory of medication-related osteonecrosis is that drugs directly negatively affect fibroblasts producing toxicity of the oral mucosa. In vitro studies, increased apoptosis has been reported, especially in oral epithelial cells, after application bisphosphonates. Bone exposure and impaired healing caused by tissue toxicity play an important role in the development of osteonecrosis [38].
