Amoxicillin bone penetration in patients with medication-related osteonecrosis of the jaw: A preliminary study

Medication-related osteonecrosis of the jaw (MRONJ) is associated with altered bone perfusion and impaired drug delivery. This study aimed to compare amoxicillin exposure in plasma and bone tissue between patients with MRONJ and controls undergoing oral surgery.

Twenty-seven patients treated with bisphosphonates or denosumab were enrolled between 2022 and 2024. Twelve patients with MRONJ were classified as cases, while fifteen were controls. Baseline characteristics, antibiotic regimens, and amoxicillin concentrations in plasma and bone tissue were considered. Drug concentrations were normalized for the administered dose. Samples with undetectable drug levels were excluded from analysis.

Cases and controls were comparable in age, sex, body mass index, hematochemical parameters, and duration of antibiotic therapy. Median dose-adjusted plasma concentrations of amoxicillin were similar between cases (3.8 [2.8-4.5] mg/L/g) and controls (4.0 [3.0-4.8] mg/L/g amoxicillin, p = 0.533). In contrast, bone amoxicillin dose-adjusted concentrations were significantly lower in cases (0.9 [0.2-3.1] ng/mg/g amoxicillin) compared to controls (15.5 [8.7-17.9] ng/mg/g amoxicillin, p = 0.004). The bone-to-plasma ratio showed a non-significant trend toward lower values in MRONJ patients (49% vs 298%, p = 0.133). Despite similar systemic exposure, amoxicillin bone concentrations were significantly reduced in MRONJ patients, suggesting impaired local drug delivery potentially related to necrosis and poor vascularization.

This exploratory study highlights the need for personalized antibiotic strategies in MRONJ management and provide a pharmacokinetic rationale for the reduced efficacy of beta-lactams in this clinical setting.