title: A mechanistic study of the interaction of water-soluble borate glass with apatite-bound heterocyclic nitrogen-containing bisphosphonates.
abstract: Long-term oral and intravenous use of nitrogen-containing bisphosphonates (N-BPs) is associated with osteonecrosis of the jaw. Although N-BPs bind strongly to bone surfaces via non-covalent bonds, it is possible for extrinsic ions to dissociate bound N-BPs from mineralized bone by competitive desorption. Here, we investigate the effects and mechanism of using an ionic cocktail derived from borate bioactive glass for sequestration of heterocyclic N-BPs bound to apatite. By employing solid-state and solution-state analytical techniques, we confirmed that sequestration of N-BPs from bisphosphonate-bound apatite occurs in the presence of the borate-containing ionic cocktail. Simulations by density functional theory computations indicate that magnesium cation and borate anion are well within the extent of the risedronate or zoledronate anion to form precipitate complexes. The sequestration mechanism is due to the borate anion competing with bisphosphonates for similar electron-deficient sites on the apatite surface for binding. Thus, application of the borate-containing ionic cocktail represents a new topical lavage approach for removing apatite-bound heterocyclic N-BPs from exposed necrotic bone in bisphosphonate-related osteonecrosis of the jaw.
  
  
  CONCLUSIONS
  Long-term oral consumption and injections of nitrogen-containing bisphosphonates (N-BPs) may result in death of the jaw bone when there is traumatic injury to the bone tissues. To date, there is no effective treatment for such a condition. This work reported the use of an ionic cocktail derived from water-soluble borate glass microfibers to displace the most potent type of N-BPs that are bound strongly to the mineral component on bone surfaces. The mechanism responsible for such an effect has been identified to be cation-mediated complexation of borate anions with negatively-charged N-BPs, allowing them to be released from the mineral surface. This borate-containing cocktail may be developed into a novel topical rinse for removing mineral-bound N-BPs from exposed dead bone.
authors.affiliation: School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Chandrani
authors.initials: C
authors.lastname: Pramanik
authors.affiliation: School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Parveen
authors.initials: P
authors.lastname: Sood
authors.affiliation: State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: He
authors.initials: H
authors.lastname: Yuan
authors.affiliation: School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Sushanta
authors.initials: S
authors.lastname: Ghoshal
authors.affiliation: Institute of Electronic and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: Henderson
authors.affiliation: School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: SeungSoon.Jang@mse.gatech.edu.
authors.forename: Seung Soon
authors.initials: SS
authors.lastname: Jang
authors.affiliation: School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: satish.kumar@gatech.edu.
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.affiliation: College of Graduate Studies, Augusta University, Augusta, GA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Pashley
authors.affiliation: College of Graduate Studies, Augusta University, Augusta, GA, USA. Electronic address: ftay@gru.edu.
authors.forename: Franklin R
authors.initials: FR
authors.lastname: Tay
mesh_terms: D001031:Apatites / Q000737:chemistry; D001842:Bone and Bones / Q000473:pathology; D001881:Borates / Q000737:chemistry; D002113:Calcification, Physiologic; D002412:Cations / Q000737:chemistry; D003198:Computer Simulation; D004164:Diphosphonates / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D005898:Glass / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D007568:Jaw / Q000473:pathology*; D008274:Magnesium / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009584:Nitrogen / Q000737:chemistry*; D010020:Osteonecrosis / Q000517:prevention & control*; D011522:Protons; D012995:Solubility; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction; D000077211:Zoledronic Acid
chemical_list: D001031:Apatites; D001881:Borates; D002412:Cations; D004164:Diphosphonates; D007093:Imidazoles; D007477:Ions; D011522:Protons; D014867:Water; D000077211:Zoledronic Acid; D017886:Durapatite; D008274:Magnesium; D009584:Nitrogen
keywords: Bisphosphonate; Borate bioactive glass; Density functional theory; Ionic cocktail