Successful treatment of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) patients with sitafloxacin: New strategies for the treatment of BRONJ

Abstract

BRONJ has become a well-known, occasionally severe side effect of bisphosphonate therapy, as well as a clinical problem. Although treatment recommendations exist, no standard therapy has yet been established for BRONJ. Also, these recommendations identify several limitations that prevent clinicians from confidently diagnosing BRONJ. The aim of the present study was to establish a treatment approach in which all patients with exposed, infected bone or intraoral/extraoral fistulas were treated with sitafloxacin (STFX). We examined 20 BRONJ patients, fourteen with cancer and six with osteoporosis. We used the current updated definition of BRONJ (12), except that we included patients who had shown symptoms for a minimum of only one month, rather than two months. Thus half of our patients had infection with no exposed, necrotic bone in the oral cavity. We purposely excluded all patients exhibiting no signs of infection (current Stages 0 and 1). In addition, each potentially causative organism was isolated from pus collected from an intraoral or extraoral fistula in ten patients on their first visit to our department. 90% of the patients had received a course of treatment with common antibiotics. STFX was administered to all patients. We then re-evaluated the lesion every other week, to determine whether epithelialization was present. We recommended surgical treatment for cases without epithelialization within 4 weeks after the onset of administration of STFX even if bone was not exposed at the lesion. 19 of our 20 cases of Stages 2-3 BRONJ responded to 2-10 weeks of STFX treatment by entering either a remission or healed phase. While surgery was done on thirteen cases, seven others reached such phases without surgery. Every patient had at least one bacterial species that showed resistance to common antibiotics. All species in all patients were susceptible to STFX. Our results indicate that STFX, with or without minor surgery, gives a high probability of controlling infection in BRONJ patients with persistent infection after use of common antibiotics, leading to remission and/or complete healing in 95% of patients.

Bisphosphonate-related osteonecrosis of the jaw: from the sine qua non condition of bone exposure to a non-exposed BRONJ entity

“…They found significantly more severe sclerosis in patients with BRONJ compared with the control group. It was also observed that the degree of sclerosis increased with the clinical stage of BRONJ, disagreeing with Hamada et al 38 Bone sclerosis, which is visualized as the loss of contrast definition between cortical bone and bone marrow space, 27,36 has been reported as the most significant early imaging sign of BRONJ. 16,19,27,29,30,36 It has been used as a criterion for non-exposed BRONJ because of its high prevalence at sites indicated by patients as symptomatic.…”

“…Other reports point to CT as the best examination for diagnosing BRONJ at early stages, since it has a higher definition and better performance than panoramic radiography. 27,30,36,38,42,43 Nevertheless, according to some authors, all patients under bisphosphonate therapy should initially undergo panoramic radiography and afterwards further examinations if needed. 37,44 For the early detection of BRONJ, Hamada et al 38 recommend CT analysis of cancellous bone radiodensity.…”

“…Therefore, the expression medicationrelated osteonecrosis of the jaw was suggested to replace BRONJ, defining the disorder as an area of exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region, persistent for more than 8 weeks in a patient under therapy or with history of antiresorptive or antiangiogenic medication who has never been subjected to head and neck radiation therapy and without metastatic disease to the jaws. 22 Ikeda et al, 36 in a series of 20 cases, found 12 patients without necrotic bone exposure who were classified as Stage 3 according to the updated AAOMS guidelines of 2014, 22 because they had extraoral and intraoral fistulae and strong associated pain. On the basis of these findings, the authors emphasized the importance of the correct staging of the patients for choosing proper treatment.…”

Bone necrosis associated with the use of bisphosphonates: Case report

“…Risk factors mainly include: injuries associated with treatment in dental surgery, use of mismatched prosthetic restorations, presence of bone exostosis, odontogenic inflammations, poor oral hygiene, coexisting diabetes, simultaneous chemotherapy and/or steroid treatment, malnutrition and smoking. [13][14][15] The route of BP administration has a great impact. The risk of BRONJ is greater for intravenous therapy (0.8-15%).…”

Sunitinib és zoledronsav által indukált állcsont-osteonecrosis

“…Második stádium: Amikor az 1. stádium képéhez társul a területet övező lágy részek gyulladása és fájdalom. Harmadik stádium: A 2. stádium képéhez kapcsolódik minimum egy az alábbi súlyos elváltozások közül, úgymint patológiás csonttörés, extraoralis fi stula, a crista zygomaticoalveolaréig, a ramus mandibulaeig, az arcüregig vagy a mandibula bázisáig terjedő necrosis, radiológiailag kimutatható nagymértékű osteolysis [8]. A stádiumbeosztástól függően különböző konzervatív, illetve sebészi kezelési stratégiákat is ajánlanak, de ezzel kapcsolatban egységes állásfoglalás még nem született [4,9].…”