Low-Intensity Pulsed Ultrasound Prevents Development of Bisphosphonate-Related Osteonecrosis of the Jaw-Like Pathophysiology in a Rat Model

Kouki Hidaka; Yuko Mikuni-Takagaki; Satoko Wada-Takahashi; Makiko Saita; Ryota Kawamata; Takenori Sato; Akira Kawata; Chihiro Miyamoto; Yojiro Maehata; Hirotaka Watabe; Nobuyuki Tani-Ishii; Nobushiro Hamada; Shun-Suke Takahashi; Shinji Deguchi; Ryohei Takeuchi

doi:10.1016/j.ultrasmedbio.2019.02.015

Low-Intensity Pulsed Ultrasound Prevents Development of Bisphosphonate-Related Osteonecrosis of the Jaw-Like Pathophysiology in a Rat Model

Ultrasound Med Biol. 2019 Jul;45(7):1721-1732. doi: 10.1016/j.ultrasmedbio.2019.02.015. Epub 2019 Apr 18.

Authors

Affiliations

¹ Department of Oral Science, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan; Department of Oral Interdisciplinary Medicine, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan.
² Department of Oral Science, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan. Electronic address: takagaki@kdu.ac.jp.
³ Department of Oral Science, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan.
⁴ Department of Oral Interdisciplinary Medicine, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan.
⁵ Department of Dentomaxillofacial Diagnosis and Treatment, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan.
⁶ Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan.
⁷ Department of Oral Science, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan; Joint Surgery Center, Kawasaki Saiwai Hospital, Kawasaki, Japan.

PMID: 31006496
DOI: 10.1016/j.ultrasmedbio.2019.02.015

Abstract

We developed a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ) by removing a maxillary molar tooth (M1) from ovariectomized rats after treatment with alendronate. To mimic periodontitis, some of the rats were administered Porphyromonas gingivalis (p. gingivalis) at the M1 site every 2 to 3 d for 2 wk. Rats pretreated with alendronate plus p. gingivalis showed delayed healing of socket epithelia, periosteal reaction of alveolar bone formation and lower bone mineral density in the alveolus above adjacent M2 teeth. These abnormalities were prevented by tooth socket exposure to 20 min/d low-intensity pulsed ultrasound (LIPUS), which restored diminished expression of RANKL, Bcl-2, IL-6, Hsp70, NF-κB and TNF-α messenger ribonucleic acids in remote bone marrow, suggesting LIPUS prevented development of BRONJ-like pathophysiology in rat by inducing systemic responses for regeneration, in addition to accelerating local healing. Non-invasive treatment by LIPUS, as well as low-level laser therapy, may be useful for medication-related osteonecrosis of the jaw patients.

Keywords: Alendronate; Bisphosphonate-related osteonecrosis of the jaw (BRONJ); Bone marrow; Low-intensity pulsed ultrasound (LIPUS); Periodontitis; Systemic effect.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bisphosphonate-Associated Osteonecrosis of the Jaw / physiopathology
Bisphosphonate-Associated Osteonecrosis of the Jaw / prevention & control*
Disease Models, Animal
Female
Osteogenesis / physiology*
Periodontitis / therapy*
Rats
Rats, Wistar
Tooth Socket / physiopathology*
Ultrasonic Therapy / methods*
Ultrasonic Waves*