Departmental Papers (Dental)

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Journal Article

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Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology





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Objective: We hypothesized that patients with bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) accumulate higher levels of BP in bone than those without BRONJ. Study Design: Using the Pmetrics package and published data, we designed a population pharmacokinetic model of pamidronate concentration in plasma and bone and derived a toxic bone BP threshold of 0.2 mmol/L. With the model, and using patient individual BP duration and bone mineral content estimated from lean body weight, we calculated bone BP levels in 153 subjects. Results: Mean bone BP in 69 BRONJ cases was higher than in 84 controls (0.20 vs 0.10 mmol/L, P < 0.001), consistent with the toxic bone threshold of 0.2 mmol/L. BRONJ was also associated with longer duration BP therapy (5.3 vs 2.7 years, P < 0.001), older age (76 vs 70 years, P < 0.001), and Asian race (49% vs 14%, P < 0.001). Conclusions: Our model accurately discriminated BRONJ cases from controls among patients on BP therapy. © 2013 Elsevier Inc.


At the time of publication, author Anh D. Le was affiliated with Ostrow School of Dentistry, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.


MeSH Aged, Aged, 80 and over, Bisphosphonate-Associated Osteonecrosis of the Jaw, Bone and Bones, Bone Density Conservation Agents, Case-Control Studies, Diphosphonates, Female, Humans, Jaw Diseases, Male, Middle Aged, Regression Analysis, Risk Assessment EMTREE drug terms bisphosphonic acid derivative, bone density conservation agent, pamidronic acid EMTREE medical terms aged, article, bone, case control study, chemically induced disorder, female, human, jaw disease, jaw osteonecrosis, male, metabolism, middle aged, regression analysis, risk assessment, very elderly



Date Posted: 10 February 2023

This document has been peer reviewed.