**4.6 Low pH values**

Depending on the pH value, bisphosphonates can bind to hydroxyapatite in the bone or leave it and activate. At neutral pH the bisphosphonates are bound to hydroxyapatite and at reduced pH values bisphosphonates are released and activated from it [37, 38]. Bone resorption mechanism takes place in the Howship's lacunae. In situations when the pH remains low, potentially leads to toxic levels of bisphosphonates which have a negative effect on osteoclasts and other cells as well. By acting on different types of cells, there is suppression of remodeling, suppression of angiogenesis, increasing the toxicity of the oral mucosa, which contributes creating an infection with developing the osteonecrosis [38].
