title: Alendronate binds to tooth root surfaces and inhibits progression of feline tooth resorption: a pilot proof-of-concept study.
abstract: Tissue distribution, bioavailability, and efficacy of alendronate in preventing progression of resorption of teeth were evaluated in cats. [Butyl-4-14C-]-alendronate accumulates on subgingival tooth and alveolar bone surfaces adjacent to vascularized tissue resulting in concentration of the drug around tooth roots. Three cats were treated with a 0.03 mg/kg i.v. bolus of [butyl-4-14C-]-alendronate followed by blood, urine, and feces collection and euthanasia 24-hours later. Drug tissue distribution was accessed by autoradiography and sample combustion. To assess bioavailability, 12 cats were administered alendronate orally (3.0 or 9.0 mg/kg in water or 9.0 mg/kg in tuna water) and urine was collected for 24-hours. In these formulations, alendronate oral bioavailability in cats was approximately 3%. In addition, 10 cats with radiographic evidence of pre-existing tooth resorption (14 affected teeth) were treated with vehicle or 3.0 mg/kg alendronate per os once weekly for 22-weeks and, then, 9.0 mg/kg per os twice weekly for 27-weeks in a random, masked study. Radiographic area of resorption was measured and progression scored every 3 to 4-months. In placebo-treated cats, resorption progressed in five of six teeth (+ 97% average increase in area of resorption), whereas progression of resorption was seen in only three of eight affected teeth in alendronate-treated cats with a -22% average change (decrease) in area (P < 0.01 difference in number of teeth showing progression; P < 0.001 difference in area of resorption). Alendronate accumulated preferentially on subgingival tooth surfaces and adjacent alveolar bone and, at a dose of 9 mg/kg twice weekly, effectively slowed or arrested the progression of resorption.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065-0900, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Mohn
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jacks
authors.forename: Klaus Dieter
authors.initials: KD
authors.lastname: Schleim
authors.forename: Colin E
authors.initials: CE
authors.lastname: Harvey
authors.forename: Bonnie
authors.initials: B
authors.lastname: Miller
authors.forename: Bruce
authors.initials: B
authors.lastname: Halley
authors.forename: William P
authors.initials: WP
authors.lastname: Feeney
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hill
authors.forename: Gerry
authors.initials: G
authors.lastname: Hickey
mesh_terms: D019386:Alendronate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002371:Cat Diseases / Q000517:prevention & control*; D002415:Cats; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D010865:Pilot Projects; D014018:Tissue Distribution; D014091:Tooth Resorption / Q000517:prevention & control / Q000662:veterinary*; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D019386:Alendronate