INTRODUCTION: Long-term administration of bisphosphonates (BPs) may cause osteonecrosis of the jaw (BRONJ). After administration, 50% of BPs in the circulation rapidly binds to calcium phosphate of bone. Two forms, bound and free BPs, may affect cells residing in bone including macrophages. Therefore, the aim of this study was to examine the effects of bound and free BPs on macrophage viability. MATERIALS AND METHODS: Biomaterials coated with BPs were used as a model to investigate the effect of bound BPs. For free BPs, RAW cells were plated on uncoated materials and BPs were added into the media. Cell viability and number were investigated by MTT assay and nuclei staining, respectively. Furthermore, coating and washing media were collected and were used to examine cell viability. RESULTS: RAW cells grew on biomaterials for 7 days. At 3 days, free and calcium-bound BPs significantly decreased cell viability and cell number compared to control. Coating media collected from pre-incubation with BP-coated composite materials reduced macrophage cell viability. CONCLUSION: This study showed that macrophages were directly affected by bound and free BPs. The presence of macrophages is mandatory for bone healing, thus the inhibition of cell viability might serve as an etiology of BRONJ.
INTRODUCTION: Long-term administration of bisphosphonates (BPs) may cause osteonecrosis of the jaw (BRONJ). After administration, 50% of BPs in the circulation rapidly binds to calcium phosphate of bone. Two forms, bound and free BPs, may affect cells residing in bone including macrophages. Therefore, the aim of this study was to examine the effects of bound and free BPs on macrophage viability. MATERIALS AND METHODS: Biomaterials coated with BPs were used as a model to investigate the effect of bound BPs. For free BPs, RAW cells were plated on uncoated materials and BPs were added into the media. Cell viability and number were investigated by MTT assay and nuclei staining, respectively. Furthermore, coating and washing media were collected and were used to examine cell viability. RESULTS: RAW cells grew on biomaterials for 7 days. At 3 days, free and calcium-bound BPs significantly decreased cell viability and cell number compared to control. Coating media collected from pre-incubation with BP-coated composite materials reduced macrophage cell viability. CONCLUSION: This study showed that macrophages were directly affected by bound and free BPs. The presence of macrophages is mandatory for bone healing, thus the inhibition of cell viability might serve as an etiology of BRONJ.
Authors: Danila S de Alexandria Santos; Marco Vinícius de Sales Lima; Alexandre do Prado Scherma; Dárcio Kitakawa; Natália de Castro Magalhães; Felipe da Silva Peralta; Luis Felipe das Chagas E Silva de Carvalho Journal: Am J Case Rep Date: 2020-11-17