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.
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.
Authors: Fabio La Ferla; Elisa Paolicchi; Francesco Crea; Silvia Cei; Filippo Graziani; Mario Gabriele; Romano Danesi Journal: Biomark Med Date: 2012-04 Impact factor: 2.851
Authors: Christoph Schaudinn; Amita Gorur; Paul Webster; Allan C Jones; Michael Neely; Roger W Jelliffe; Anh D Le; Parish P Sedghizadeh Journal: Oral Surg Oral Med Oral Pathol Oral Radiol Date: 2012-10
Authors: Parish P Sedghizadeh; Shuting Sun; Adam F Junka; Eric Richard; Keivan Sadrerafi; Susan Mahabady; Neema Bakhshalian; Natalia Tjokro; Marzenna Bartoszewicz; Monika Oleksy; Patrycja Szymczyk; Mark W Lundy; Jeffrey D Neighbors; R Graham G Russell; Charles E McKenna; Frank H Ebetino Journal: J Med Chem Date: 2017-02-13 Impact factor: 7.446
Authors: Parish P Sedghizadeh; Shuting Sun; Allan C Jones; Esmat Sodagar; Philip Cherian; Casey Chen; Adam F Junka; Jeffrey D Neighbors; Charles E McKenna; R Graham G Russell; Frank H Ebetino Journal: Bone Date: 2021-03-20 Impact factor: 4.626