Bisphosphonate-associated osteonecrosis (BRONJ) is an adverse event associated with bisphosphonate drug treatment. An 81-year-old female has been taking bisphosphonates orally once a month for three years complained of pain in the left mandibular molar area after implant placement. Tenderness and fistula were formed. Extensive osteosclerosis in posterior area of the left mandible and bone resorption around distal side of #37i were shown on radiographs. She was given oral antibiotics for 6 weeks and bone resorption was improved. A 70-year-old male had a history of intravenous injection of bisphosphonates for blood cancer complained of #46i implant mobility. There was buccal fistula on #45 site. Radiographically, severe bone resorption and extensive osteosclerosis were shown. He was treated with removal of implant and inflammatory tissue. Patients who have taken bisphosphonates may develop BRONJ after tooth extraction or implant placement and are needed to meticulous plaque control for preventing BRONJ.

The purpose of this study was to identify the oral bacterial species in sequestra from patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). Fifteen patients with BRONJ (2 males and 13 females) were evaluated. Clinical features, radiographic findings, and bisphosphonate intake history were investigated. All patients were treated with surgical methods (curettage or sequestrectomy). Infected bone samples were collected from the affected BRONJ site. Ten bacterial species were selected for polymerase chain reaction (PCR) detection. Two to nine bacterial species were detected by PCR. Gram-negative species were predominant and all identified bacteria were anaerobes. Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were detected at high levels. These are major pathogenic species in periodontal disease. Orthopantomographic radiographs showed generalized alveolar bone loss in most patients. These radiographic findings may provide evidence of chronic periodontitis as a pre-existing inflammatory disease. Most patients had experienced a predisposing dental procedure, such as tooth extraction. Sequestra (necrotic bone) infected with oral bacterial species may be an important risk factor for BRONJ. As such, prevention and management of BRONJ may rely on effective control of bacteria in the oral cavity.

The purpose of this study is to evaluate the clinical and radiographic features of Bisphosphonate-related osteonecrosis of the jaws(BRONJ). The clinical and radiographic features of 27 patients diagnosed with BRONJ from 2008 to 2012 were evaluated on the basis of the charts and panoramic radiographs and cone beam computed tomographs. As for clinical features, the following contents were evaluated; type of dental treatments before occurrence of BRONJ, the cause of taking bisphosphonate medicine, undergoing dental treatment, interval between dental treatments and symptom expression. As for radiological features, location of BRONJ, size of bone destructions and sclerosing of the surrounding bone, locational relationship between mandibular canal and inferior border of bone destruction, and effect on the maxillary sinus. In clinical features, extraction was done in 18 patients(66.7%), as the most common dental treatment before occurrence of BRONJ. The most common cause of taking bisphosphonate medicine was osteoporosis(20 pateints, 70.4%). The patients treated during bisphosphonate administration was 17(63.0%). The interval between dental treatments and symptom in the most patients(14 patients, 51.8%) was within 1 month. In radiological features, sequestrum was seen in 11 patients(40.7%) and bony sclerosing in 15(55.6%). The mean width of sclerosing was 32.9±12.4mm and mean height 17.5±4.4mm. Bone destruction invaded to inferior border of mandibular canal in 88.2%(15 among 17 mandibles),. Maxillary sinusitis was diagnosed in 57.1% among the evaluated maxillae(4 among 11 maxillae). In diagnosing BRONJ, clinicians should be cautious about medical history of patients and have well-knowledge of radiographic features.

The prolonged bisphosphonate (BP) uptakes are frequently resulted in BP-related osteonecrosis of jaws (BRONJ). The previous study reported that the BP-involved bones were stained blue by Masson trichrome and showed weak birefringence compared to the normal bone1). Using the representative twenty cases of BRONJ osteomyelitis the present study examined the ultrastructure of BP-involved bone by scanning electron microscope (SEM) using decalcified bone microsections. As the BP-involved bones showed different features from adjacent normal bone by blue staining in Masson trichrome method and by rare birefringence under polarizing microscope, the ultrastructure of BP-involved bone matrixes were distinguishable histologically in comparison with normal bone. The normal bone showed the tight attachment of interdigitating dendritic bone matrixes, producing many Haversian canaliculi, while the BP-involved bone showed the compact alignment of granular bone matrixes, resulted in the abortive Haversian canaliculi. The osteocytes in the lacunar spaces of BP-involved bone became shrunken and necrotic, and the BP-involved bone showed many tunnel-like spaces produced by direct chemical resorptions and proteolytic degradation of bone matrixes. Taken together, it was conspicuous that the BP-involved bones were abnormal in their stainability of Masson trichrome, birefringence under polarizing microscope, and ultrastructure under SEM. These findings of BP-involved bone may have an implication for the pathogenetic roles of BRONJ, and can be applicable for the differential diagnosis of BRONJ from other osseous lesions.

A case of chronic osteomyelitis caused by prolonged intake of bisphosphonate showed multiple recurrences involving extensive area of mandibular body. After saucerization the removed bony fragments were decalcified, microsected in 4 ㎛ thickness, and stained with hematoxylin and eosin, Masson trichrome, von Gieson, and periodic acid Schiff reaction. The inflammatory lesion contained fragile osteophytes easily propagated into sequestra. Histologically, this osteomyelitis was relatively less suppurative but almost granulomatous, highly infiltrated with small round cells and macrophages. The osteophytes were frequently deposited on the old lamellate bone, but their ossification was extremely immature and frequently filled with sclerosed collagen bundles positive for von Gieson stain. In the polarizing microscope observation under Masson trichrome stain the newly deposited osteophytes were lack of birefringence image of Haversian system contrast to the old bone nearby. Therefore, we presume that the prolonged intake of bisphosphonate may induce the immature osteophytes lack of Harversian system, which are partly filled with sclerotic collagen bundles, and the immature bone is easily undergone extensive degeneration and necrosis, resulted in the inflammatory foci for multiple recurrent osteomyelitis.