title: Ibandronate uptake in the jaw is similar to long bones and vertebrae in the rat.
abstract: Intravenous bisphosphonates may be involved in the development of osteonecrosis of the jaw (ONJ). However, a mechanistic causality has not been demonstrated. To evaluate whether there is higher drug uptake by the jaw versus other bones that might be involved in ONJ pathogenesis, we performed a pilot experiment comparing ibandronate uptake in rat mandible, femur, and lumbar vertebrae after repeated administration. Rats (n = 1/group) received daily subcutaneous injections of ibandronate in doses ranging from 0.003 to 0.3 mg/kg/day for 9 days. Five days after the last injection, the animals were killed and the right femur, lumbar vertebrae L3-L5, and the right mandible were removed. After cleaning and drying, bone dry weight was recorded, and ibandronate concentration was determined in whole-bone hydrolyzates by gas chromatography mass spectrometry. Concentrations of ibandronate increased dose-dependently in all bones with similar concentrations per bone at each dose level ranging from values below quantification limit (low dose) up to approximately 10 ng ibandronate/mg bone dry weight (high dose). In this rat study, there was a relatively similar bisphosphonate uptake between the femur and lumbar vertebrae bones whereas the uptake in the jaw was statistically smaller with regard to the absolute values (P < 0.05). Thus, there is no suggestion of preferential bisphosphonate uptake in the jaw.
authors.affiliation: Department of Pharmacology, Pharma Research Penzberg, Roche Diagnostics GmbH, Nonnenwald 2, Building 231 / Room 579, D-82377 Penzberg, Germany. frieder.bauss@roche.com
authors.forename: Frieder
authors.initials: F
authors.lastname: Bauss
authors.forename: Thomas
authors.initials: T
authors.lastname: Pfister
authors.forename: Socrates
authors.initials: S
authors.lastname: Papapoulos
mesh_terms: D000818:Animals; D004164:Diphosphonates / Q000493:pharmacokinetics* / Q000494:pharmacology; D005269:Femur / Q000187:drug effects / Q000378:metabolism*; D000077557:Ibandronic Acid; D007568:Jaw / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013131:Spine / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004164:Diphosphonates; D000077557:Ibandronic Acid