Long-chain functional bisphosphonates: synthesis, anticalcification, and antiresorption activity

Abstract

Bisacylphosphonates have previously been shown to possess in vitro activity with regard to hydroxyapatite (HAP) formation and dissolution, and in vivo on tissue calcification and bone resorption. This work was aimed at elucidating the role of the keto groups in the biological activity of these compounds. For this purpose, we have synthesized a series of long‐chain bisphosphonates possessing different functional groups adjacent to the phosphonic functions and examined them in some in vitro and in vivo models. The functional groups introduced into the newly synthesized bisphosphonates (hydroxyl, amide, and difluoromethylene) were chosen as to represent certain isolated aspects of the keto groups in the original compounds. None of the functional groups introduced into the long chain bisphosphonates bestowed higher activity on the molecules than the carbonyl groups. The unique effect of the α‐keto groups in rendering long‐chain bisphosphonates active is presumably attained through a combination of chelating ability with sufficiently low pKa values to enable the bisacylphosphonate molecules to be fully ionized at physiological pH. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:470–479, 2000

Case Report: Reconstruction of a Large Maxillary Defect With an Engineered, Vascularized, Prefabricated Bone Graft

“…Further studies are therefore required to identify the underlying cause of bone resorption and to possibly counteract it. For example, combined anti-resorptive therapies, such as bisphosphonates, have been preclinically validated in a variety of bone repair models, especially to reduce BMP catabolic effects (48)(49)(50)(51), and may be considered in future developments. More bone mass would allow the patient to receive tooth implants after the primary procedure and without need of additional bone transfer to the defect site.…”