title: Proton pump inhibitors control osteoclastic resorption of calcium phosphate implants and stimulate increased local reparative bone growth.
abstract: Calcium phosphate (CAP) rods and pastes based on dicalcium and tetracalcium phosphate chemistry were modified with a specific osteoclast proton pump inhibitor, Bafilomycin A(1), and implanted in the distal femurs of young male Wistar rats for 7, 10, and 14 days. The extent of osteoclastic resorption of these materials and the amount of regenerative bone formed were qualitatively evaluated. Resorptive activity similar to the remodeling process of natural bone was observed in the controls. In contrast, the resorption of materials containing Bafilomycin A(1) was considerably lower, even though tartrate-resistant acid phosphatase-positive osteoclasts were present at the tissue/material interface. A greater amount of newly formed bone consistently surrounded the CAP rods and pastes containing Bafilomycin A(1) in comparison to the control specimens, which indicated that this reparative bone was not resorbed as quickly as the new bone surrounding the controls. Increased local bone mass around the Bafilomycin A(1)-modified materials resulted from the diffusion of the proton pump inhibitor into the biological tissue at the defect site. Thus, through inhibition of the osteoclast proton pump, Bafilomycin A(1) slowed down not only the resorption of the implant material but also the resorption of the newly formed reparative bone, which resulted in an increased local bone mass.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, 4 Taddle Creek Road, Toronto, Ontario M5S 3G9, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Rzeszutek
authors.forename: F
authors.initials: F
authors.lastname: Sarraf
authors.forename: J E
authors.initials: JE
authors.lastname: Davies
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001843:Bone Cements / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000378:metabolism; D018786:Bone Substitutes / Q000494:pharmacology; D002130:Calcium Phosphates / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018942:Macrolides; D008297:Male; D016348:Osseointegration / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D018786:Bone Substitutes; D002130:Calcium Phosphates; D004791:Enzyme Inhibitors; D018942:Macrolides; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases