The purpose of this translational study was to investigate the role a high calcium phosphate (CaPO 4 ) therapy has in neutralizing local acidic pH, inducing bisphosphonate (BP) scavenging and inhibiting connective tissue fibrosis; to reduce the effect zoledronic acid (ZA) has on oral soft tissues, thereby leading to ONJ. Saliva from patients using or not using a BP; and with or without ONJ was measured for pH. Fibroblast and keratinocyte cell lines were exposed to ZA (0.5–10 μM), acidity 5.5–7.0 pH and high CaPO 4 solution. We used visual inspection; TUNEL; immunohistochemistry; survivin, caspase 3, cleaved caspase 9 and Ki-67 expression; MTS; scratch migration; and flow cytometry assays to measure the effects of ZA and ZA plus CaPO 4 . The results show that patients with ONJ have more acidic saliva than those taking a BP without ONJ or in those not taking a BP. Additionally, immunohistochemistry and Western blot shows the soft tissue surrounding ONJ lesions overexpress caspase 3. Finally, ZA and acidity induce a conversion of fibroblasts to myofibroblasts, possibly inducing a localized fibrotic impairment of wound healing. Overall, CaPO 4 therapy reversed salivary acidity, the in vitro effects of ZA, and the conversion to myofibroblasts. These results demonstrate that the effect ZA and ONJ have on salivary acidity; soft tissue apoptosis, cell proliferation; and conversion to myofibroblasts can be reversed by using a supersaturated CaPO 4 solution, supporting the potential role of CaPO 4 as an adjunct therapy for ONJ by facilitating soft tissue healing.
Conflict of interest: None declared.