Abstract
Medication-related osteonecrosis of the jaw (MRONJ) represents a complication of bisphosphonate treatment that responds poorly to standard treatment. In a retrospective cohort study we investigated a possible role of Actinomyces spp. in the pathogenesis of MRONJ. Deep biopsies of necrotic bone were collected during surgical treatment of MRONJ and evaluated by histology and microbiology for the presence of Actinomyces spp. Microbiological, demographic and clinicpathological data were analyzed for risk of Actinomyces-associated MRONJ. Between 2005 and 2014, 111 patients suffering from histologically-confirmed MRONJ were identified. Actinomyces spp. were detected in 99 cases (89%) by histology and in six further patients by microbiological culture. A diverse microbial flora was found in all specimens without association with Actinomyces spp. Demographic and clinicopathological characteristics did not separate significantly Actinomyces-positive from Actinomyces-negative cases. Our observations confirm previous reports of a high prevalence of Actinomyces spp. in MRONJ in the single largest cohort available up to now. The high prevalence of Actinomyces spp. and the lack of clinicopathological risk factors underline the prominent role of Actinomyces spp. in MRONJ and may change the current understanding of MRONJ. Established prolonged antimicrobial treatment regimens against Actinomyces spp. infection could therefore be a mainstay of future MRONJ management.
Highlights
With intravenous bisphosphonates as well as combination treatment with anti-angiogenetic drugs were identified as significant risk factors for MRONJ7,8
Evidence suggesting a role of Actinomyces species in the evolution of Medication-related osteonecrosis of the jaw (MRONJ) accumulated over the past years, but these small case series and reviews revealing a high prevalence of Actinomyces spp. in MRONJ did not had impact on current treatment recommendations up to now[10,11,12,13]
The majority of MRONJ patients had a malignancy as underlying disease and most of them suffered from malignant bone disease
Summary
With intravenous bisphosphonates as well as combination treatment with anti-angiogenetic drugs were identified as significant risk factors for MRONJ7,8. Remodeling or oversuppression of bone resorption, inhibition of blood supply, constant microtrauma, dentoalveolar surgery, or local inflammation were proposed in association with bisphosphonate treatment to explain the unique localization to the jaw but none of these hypotheses explain all cases[9]. Standards of treatment for invasive actinomycosis have been developed, validated and adapted during the past five decades and is based on prolonged antimicrobial treatment for 2–6 months combined with surgery. The aim of the present study was to evaluate in a large and well-characterized cohort of patients suffering from MRONJ the incidence of Actinomyces spp. infection and possible risk-factors that may predispose patients to this infection. A large majority of the present MRONJ cases was associated with Actinomyces spp. infection
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