Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
2-2013
Publication Source
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Volume
115
Issue
2
Start Page
224
Last Page
232
DOI
10.1016/j.oooo.2012.08.455
Abstract
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.
Keywords
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
Recommended Citation
Sedghizadeh, P. P., Jones, A. C., Lavallee, C., Jelliffe, R. W., Le, A. D., Lee, P., Kiss, A., & Neely, M. (2013). Population Pharmacokinetic and Pharmacodynamic Modeling for Assessing Risk of Bisphosphonate-related Osteonecrosis of the Jaw. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 115 (2), 224-232. http://dx.doi.org/10.1016/j.oooo.2012.08.455
Date Posted: 10 February 2023
This document has been peer reviewed.
Comments
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.