Correspondence

Severe osteomyelitis of the jaw in long-term survivors of multiple myeloma: A new clinical entity

The AAOMS in 2014 changed from BRONJ to the term Medication-Related Osteonecrosis of the Jaw (MRONJ), because of the growing number of osteonecrosis cases associated with other antiresorptive and antiangiogenic therapies. Even if the drugs involved are different, the histopathological findings are the same. Colonies of Actinomyces are encountered in most cases. The aim of the present study is to report on Actinomyces prevalence among the cases of MRONJ, taking into consideration also antiresorptive and antiangiogenic therapies in the literature and in our sample between 2005 and 2020.

The review was performed using the database Medline the linkage between Actinomyces infection and MRONJ. The retrospective study was conducted on patients between with clinical and radiological manifestations of MRONJ May 2005 and February 2020.

A total of 42 articles were found, 30 publications have been taken into consideration for the review. A total of 114 patients have been examined at the Padua Hospital. A total of 101 oncological patients presented the histological confirmation of MRONJ. 83 specimens revealed the presence of Actinomyces infection (82.18%).

Actinomyces-associated lesions are frequent and present a wide spectrum of clinical manifestation.

The aim of this systematic review was to answer the question: What are the treatments available for bisphosphonate-related osteonecrosis of the jaws (BRONJ) and their outcomes? A literature search of PubMed, Cochrane Library, and Web of Science databases was conducted in accordance with the PRISMA statement, search phrases were (‘jaw osteonecrosis’ OR ‘bisphosphonate-related osteonecrosis’ OR ‘bisphosphonate osteonecrosis’) AND (‘treatment’ OR ‘outcomes’). Ninety-seven articles published between 2003 and February 2014 were reviewed. The studies reported 4879 cases of BRONJ. The mean age of the patients was 66.5 ± 4.7 years. The male to female ratio was 1:2. The mean duration of bisphosphonate (BP) administration was 38.2 ± 15.7 months. The quality of the publications was good, with some moderate and poor. Minimally invasive surgical treatment was the treatment most used. Medical treatment was also used. Adjunctive treatments included laser, growth factors, hyperbaric oxygen and ozone. The articles provided a broad range of outcome variables to assess the treatment of BRONJ and the outcomes of each treatment. Considerable heterogeneity was found regarding study design, sample size, and treatment modalities. Clinical trials with larger samples are required to provide sufficient information for each treatment modality to predict the outcomes of each treatment.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an important side effect of bisphosphonates, whose etiopathogenesis has not been completely elucidated. Theories pointing to bone turnover and angiogenesis inhibition, as well as effects on epithelial cells of oral mucosa and the role of microorganisms have been reported. Nevertheless, the true contribution of each one of these factors to BRONJ is unknown. We present here a literature review focusing on important aspects regarding the role of microorganisms in BRONJ development. Knowledge about specific microbiota and its role in the etiopathogenesis of this disease can help the optimisation of preventive and therapeutic interventions in patients with or at-risk for BRONJ.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) appears to be refractory to conventional treatment approaches. We offer our experiences and treatment strategies regarding the successful resolution of BRONJ.

Thirty sites of BRONJ in 27 patients were clinicopathologically proven. The mandible was more commonly affected than the maxilla (67% versus 33%). The appearance of 23 (77%) BRONJ sites was preceded by a tooth extraction, dental infection, or oral trauma, and the remaining sites occurred spontaneously. There was a female predilection with a ratio of 3.5:1, and 22 (81%) patients were oral bisphosphonate (BPh) users. The treatment strategies included: (1) nonsurgical treatment using antimicrobial rinses; (2) removal of necrotic bone followed by insertion of Gelfoam impregnated with tetracycline; or (3) filling with alloplastic bone substitute plus tetracycline as the procedure of guided bone regeneration (GBR); and (4) radical resection of all necrotic bone and immediate reconstruction.

In 25 (93%) patients with 27 (90%) sites, BRONJ was successfully treated. The three treatment failures were all in two intravenous BPh users. There was no significant dependence of the treatment results on the severity of BRONJ. However, there was a significant dependence of the treatment result on the route of BPh administration.

Our study demonstrates a high success rate of conservative and surgical treatment of BRONJ. This is the first reported use of GBR to successfully treat oral BPh-related osteonecrosis of the jaw. Irrigation with antimicrobial rinses may result in pain reduction, and regression or even resolution of BRONJ.

Bisphosphonates are frequently used worldwide mostly in osteoporosis and skeletal bone metastases. However, a serious side-effect is bisphosphonate related osteonecrosis of the jaws (BRONJ). The mechanism behind BRONJ remains unclear. In literature several origins are suggested. Presence of the teeth in the jaws may play an important role. Therefore in this study 45 patients were analyzed retrospectively.

Files of 45 patients with a diagnosis of BRONJ were analyzed, meaning clinical features, bisphosphonate use, dental history including luxating moment and (previous) treatment.

In 97.5% (n = 44) a certain or presumable dental focus, such as extractions, a previous dental treatment or prosthesis complaints were found as initiating factor of BRONJ.

In contrast to findings in literature, in our group of patients a dental focus was found in 44 of 45 cases. This implies a dentoalveolar start of BRONJ with subsequent spreading into the jaws in nearly all cases.

Clinical findings of bisphosphonate-related osteonecrosis of the jaws (BRONJ) largely overlap with chronic osteomyelitis of the jaws (COMJ). This study analyzed the clinical and radiological differences between BRONJ and COMJ.

The clinical, radiological and scintigraphic findings of 60 female BRONJ patients were analyzed and compared to 37 female COMJ patients. Patients with cancer, metastatic bone disease, or a history of chemotherapy or radiotherapy were excluded from the study because of the potential effect on the radiographic findings.

The radiographic invasiveness of BRONJ at a local site was related to the advanced stages of BRONJ. A major clinical difference between BRONJ and COMJ was bone exposure (100% and 16%, respectively). BRONJ occurred at more multiple sites and showed a more osteolytic and invasive findings than that of COMJ (p < 0.05). The bone scintigraphic findings according to the radiographic findings of BRONJ and COMJ showed a similar pattern. Positive radioisotope uptake reflecting an increased osteoblastic activity pattern existed in most BRONJ (91.9%) and COMJ (94.6%) patients.

The essential clinical finding of BRONJ, bone exposure, might influence the pathophysiological condition of the bone and can explain the more advanced radiographic bone destruction and involvement of adjacent structures of BRONJ than that of COMJ. Increased radiotracer uptake in both COMJ and BRONJ lesions imply that BRONJ lesions are not ‘frozen’ and has a common finding of inflammatory response of a bone lesion.