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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545087 | PMC |
| http://dx.doi.org/10.1016/j.oooo.2012.08.455 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.
Aliment Pharmacol Ther
January 2025
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.
Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.
Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.
Effectiveness of PK-Guided Personalized Recombinant FVIII Treatment in Patients with Hemophilia A: Clinical Case Experiences Based on an Observational Study.
J Blood Med
January 2025
Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Purpose: Prophylaxis with recombinant factor VIII (rFVIII) products is the gold-standard treatment for hemophilia A. However, interindividual differences affect the half-life and clearance of rFVIII products. The myPKFiT is a web-based medical-device software program for population pharmacokinetic (PK) simulation of FVIII products to guide accurate FVIII doses and dosing intervals.
View Article and Find Full Text PDFSynthesis estimators for transportability with positivity violations by a continuous covariate.
J R Stat Soc Ser A Stat Soc
January 2025
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Studies intended to estimate the effect of a treatment, like randomized trials, may not be sampled from the desired target population. To correct for this discrepancy, estimates can be transported to the target population. Methods for transporting between populations are often premised on a positivity assumption, such that all relevant covariate patterns in one population are also present in the other.
View Article and Find Full Text PDFDirect Oral Anticoagulants in Patients With ESRD and Kidney Transplantation.
Kidney Int Rep
January 2025
Department of Pharmacy, NewYork-Presbyterian Hospital, New York, USA.
Direct oral anticoagulant (DOAC) use has significantly increased because major medical organizations endorse their role for conditions in which anticoagulation is indicated. Owing to important pharmacokinetic properties, the use of apixaban and rivaroxaban requires careful consideration in at-risk populations such as those with kidney disease. Both apixaban and rivaroxaban undergo some degree of renal elimination, and thus total drug exposure is increased in patients with renal insufficiency and/or those undergoing renal replacement therapy (RRT).
View Article and Find Full Text PDFQuantification of maternal and fetal valaciclovir exposure in a pharmacokinetic study of cytomegalovirus-infected pregnant women treated to prevent vertical transmission.
J Antimicrob Chemother
January 2025
URP 7328 Federation for Research into Innovative Explorations and Therapeutics in Utero, University of Paris-Cité, Paris, France.
Background: In cases of maternal primary infection with cytomegalovirus (CMV-MPI) maternal treatment with oral valaciclovir 8 g/day has been shown to reduce the risk of fetal infection. The pharmacological profile of this high dosage during pregnancy is not yet known.
Objectives: To quantify maternal-fetal exposure to valaciclovir 8 g/day in a population pharmacokinetic (popPK) study.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!