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.

Treatment of Ionized Hypercalcemia in 12 Cats (2006–2008) Using PO‐Administered Alendronate

“…The marked dosage differences reported among alendronate, pamidronate, and zolendronate are a consequence of the low gastrointestinal absorption of bisphosphonates. The alendronate dosage used in our study was similar to those used in other studies of alendronate 3, 11…”

“…Alendronate is poorly absorbed from the Gl tract, with oral bioavailability of 1.54 ± 0.30% when administered in water and 0.20 ± 0.03% when administered in tuna juice‐flavored water to cats 11. Alendronate that is absorbed from the GI tract is rapidly and preferentially sequestered in the skeleton or excreted unchanged by the kidneys 10.…”

“…In contrast, 2 cats required dose reduction because of development of borderline hypocalcemia. In a study investigating the use of alendronate in the treatment of 9 cats with FORL, dosages of 3 mg/kg PO q7d for 22 weeks followed by 9 mg/kg PO q3–4d for 27 weeks were administered without recognition of adverse effects 11. These dosages are much higher than zolendrate dosages used in dogs (0.25 mg/kg IV)6 or a pamidronate dosage (1.05–2.0 mg/kg IV) reported in cats 9.…”

Diagnostische Aufarbeitung und Management der Hyperkalzämie des Hundes am Beispiel des primären Hyperparathyreoidismus

“…In einer Fallsammlung von Katzen mit idiopathischer Hyperkalzämie war Alendronat ebenfalls gut verträglich und senkte den Kalziumspiegel effektiv (25). In Einzelfällen können Nebenwirkungen wie gastrointestinale Symptome, Hypokalzämie und Osteonekrosen im Kiefer auftreten (16,36 (39).…”

Dental and Oral Diseases

“…101 Systemic alendronate therapy has been suggested on the basis of results of a very small sample of cats 75 ; however, studies in mice provide evidence that dentoalveolar ankylosis and extensive tooth resorption actually result from bisphosphonate administration. 101 Systemic alendronate therapy has been suggested on the basis of results of a very small sample of cats 75 ; however, studies in mice provide evidence that dentoalveolar ankylosis and extensive tooth resorption actually result from bisphosphonate administration.…”