A mechanistic study of the interaction of water-soluble borate glass with apatite-bound heterocyclic nitrogen-containing bisphosphonates

Publication date: Available online 8 December 2015
Source:Acta Biomaterialia
Author(s): Chandrani Pramanik, Parveen Sood, Li-na Niu, He Yuan, Sushanta Ghoshal, Walter Henderson, Yaodong Liu, Seung Soon Jang, Satish Kumar, David H. Pashley, Franklin R. Tay
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 herterocyclic 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.

Graphical abstract

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NaTIpo
via IFTTT