Anatomic site variability in rat skeletal uptake and desorption of fluorescently labeled bisphosphonate.
OBJECTIVE
Bisphosphonates commonly used to treat osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy and osteolytic lesions of cancer metastasis have been associated with bisphosphonate-associated jaw osteonecrosis (BJON). The underlying pathogenesis of BJON is unclear, but disproportionate bisphosphonate concentration in the jaw has been proposed as one potential etiological factor. This study tested the hypothesis that skeletal biodistribution of intravenous bisphosphonate is anatomic site-dependent in a rat model system.


METHODS
Fluorescently labeled pamidronate was injected intravenously in athymic rats of equal weights followed by in vivo whole body fluorimetry, ex vivo optical imaging of oral, axial, and appendicular bones and ethylenediaminetetraacetic acid bone decalcification to assess hydroxyapatite-bound bisphosphonate.


RESULTS
Bisphosphonate uptake and bisphosphonate released per unit calcium were similar in oral and appendicular bones but lower than those in axial bones. Hydroxyapatite-bound bisphosphonate liberated by sequential acid decalcification was the highest in oral, relative to axial and appendicular bones (P < 0.05).


CONCLUSIONS
This study demonstrates regional differences in uptake and release of bisphosphonate from oral, axial, and appendicular bones of immune deficient rats.
Department of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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D
Wen
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Qing
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Harrison
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Golub
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Akintoye
D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents; D003648:Decalcification Technique; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017886:Durapatite / Q000378:metabolism; D004492:Edetic Acid; D005260:Female; D005269:Femur / Q000378:metabolism; D005360:Fibula / Q000378:metabolism; D005456:Fluorescent Dyes; D005470:Fluorometry; D006811:Humerus / Q000378:metabolism; D007275:Injections, Intravenous; D008334:Mandible / Q000378:metabolism; D023421:Models, Animal; D000077268:Pamidronate; D011884:Radius / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude; D013054:Spectrophotometry, Atomic; D013977:Tibia / Q000378:metabolism; D014018:Tissue Distribution; D014457:Ulna / Q000378:metabolism
D050071:Bone Density Conservation Agents; D002614:Chelating Agents; D004164:Diphosphonates; D005456:Fluorescent Dyes; D017886:Durapatite; D004492:Edetic Acid; D000077268:Pamidronate; D002118:Calcium