A soft-tissue in vitro model of bisphosphonate induced localized non-traditional calciphylaxis

Abstract

Background: Bisphosphonates (BPs) such as zoledronic acid (ZA) are widely used to treat complications of bony metastases in cancer patients. One of the serious adverse effects of ZA treatment is Bisphosphonates osteonecrosis (BON). The pathophysiologic mechanisms of BON are not fully elucidated. Scheper et al (2012) suggest that BON is correlated with a localized non-traditional calciphylaxis. In this project, we studied the effect of ZA on soft tissue by calcium deposition. Also, we hypothesized that albumin will reverse that effect. Materials and Methods: Normal Oral Keratinocytes (NOK) and Human Gingival Fibroblats (HGF) were treated by different ZA concentration and Bovine Serum Albumin (BSA). Immunoflurosence and Western Blot were used to study the treatments effects. Results: There is an increase in calcium concentration when cells were treated with ZA. However, there is a decrease when cells were treated with albumin. Conclusion: Albumin can bind to the calcium released following ZA treatment. Our finding might suggest a method of BON prevention. Further studies are needed to determine if such effects are clinically relevant for in vivo models of BON.