Kazumitsu Aoki1,2, Satoru Matsunaga1,3, Shinichirou Ito4, Takahiko Shibahara4, Takeshi Nomura3,5, Hideo Matsuzaki2, Shinichi Abe1,3, Akira Yamaguchi6,7. 1. Department of Anatomy, Tokyo Dental College, 2-9-18 Kanda-Misaki-cho, Chiyoda-ku, Tokyo, 101-0061, Japan. 2. Department of Dentistry and Oral Surgery, Tokyo Metropolitan Bokutoh Hospital, 4-23-15 kotobashi, Sumida-ku, Tokyo, 130-8675, Japan. 3. Tokyo Dental College Research Branding Project, 2-9-18 Kanda-Misaki-cho, Chiyoda-ku, Tokyo, 101-0061, Japan. 4. Department of Oral and Maxillofacial Surgery, Tokyo Dental College, 2-9-18 Kanda-Misaki-cho, Chiyoda-ku, Tokyo, 101-0061, Japan. 5. Department of Oral Oncology and Maxillofacial Surgery, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa city, Chiba, 272-8513, Japan. 6. Tokyo Dental College Research Branding Project, 2-9-18 Kanda-Misaki-cho, Chiyoda-ku, Tokyo, 101-0061, Japan. akira@tdc.ac.jp. 7. Oral Health Science Center, Tokyo Dental College, 2-9-18 Kanda-Misaki-cho, Chiyoda-ku, Tokyo, 101-0061, Japan. akira@tdc.ac.jp.
Abstract
BACKGROUND: Bisphosphonate and denosumab are widely used for the treatment of osteoporosis and bone metastasis of cancer to prevent excessive bone resorption. Osteonecrosis of the jaw is a serious adverse effect of bisphosphonate or denosumab referred to as bisphosphonate-related osteonecrosis of the jaw (BRONJ) or denosumab-related osteonecrosis of the jaw (DRONJ), respectively. Since bisphosphonate and denosumab inhibit bone resorption by different mechanism, we evaluated whether these drug types result in different histopathological characteristics related to bone resorption. MATERIALS AND METHODS: We histopathologically investigated 10 cases of BRONJ, DRONJ, and suppurative osteomyelitis. Paraffin sections prepared from decalcified dissected jaw bones were used for histopathological observation, second harmonic generation imaging, and bone histomorphometry. The samples were also observed by a scanning electron microscope. RESULTS: Numerous bone resorption lacunae were observed on the necrotic bone surface in almost all cases of BRONJ; however, such resorption lacunae were limited in DRONJ and suppurative osteomyelitis. Prominent bone resorption lacunae were also confirmed by second harmonic generation imaging and scanning electron microscopy in BRONJ, but not in DRONJ or suppurative osteomyelitis. As determined by bone histomorphometry, the number of bone resorption lacunae and the length of the erosion surface of resorption lacunae were significantly higher in BRONJ group than in the DRONJ and suppurative osteomyelitis groups. These parameters were correlated between the necrotic bones and the vital bones in BRONJ. CONCLUSIONS: Persistent bone resorption lacunae on the necrotic bone surface are unique to BRONJ, providing a basis for distinguishing BRONJ from DRONJ and OM in histopathological diagnosis.
BACKGROUND:Bisphosphonate and denosumab are widely used for the treatment of osteoporosis and bone metastasis of cancer to prevent excessive bone resorption. Osteonecrosis of the jaw is a serious adverse effect of bisphosphonate or denosumab referred to as bisphosphonate-related osteonecrosis of the jaw (BRONJ) or denosumab-related osteonecrosis of the jaw (DRONJ), respectively. Since bisphosphonate and denosumab inhibit bone resorption by different mechanism, we evaluated whether these drug types result in different histopathological characteristics related to bone resorption. MATERIALS AND METHODS: We histopathologically investigated 10 cases of BRONJ, DRONJ, and suppurative osteomyelitis. Paraffin sections prepared from decalcified dissected jaw bones were used for histopathological observation, second harmonic generation imaging, and bone histomorphometry. The samples were also observed by a scanning electron microscope. RESULTS: Numerous bone resorption lacunae were observed on the necrotic bone surface in almost all cases of BRONJ; however, such resorption lacunae were limited in DRONJ and suppurative osteomyelitis. Prominent bone resorption lacunae were also confirmed by second harmonic generation imaging and scanning electron microscopy in BRONJ, but not in DRONJ or suppurative osteomyelitis. As determined by bone histomorphometry, the number of bone resorption lacunae and the length of the erosion surface of resorption lacunae were significantly higher in BRONJ group than in the DRONJ and suppurative osteomyelitis groups. These parameters were correlated between the necrotic bones and the vital bones in BRONJ. CONCLUSIONS: Persistent bone resorption lacunae on the necrotic bone surface are unique to BRONJ, providing a basis for distinguishing BRONJ from DRONJ and OM in histopathological diagnosis.
Entities:
Keywords:
BRONJ; Bisphosphonate; Bone resorption lacunae; Denosumab; Osteonecrosis of jaw