title: Lipopolysaccharide aggravates bisphosphonate-induced osteonecrosis in rats.
abstract: The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is highly controversial. We have previously reported the development of osteonecrosis by periodontal pathogenic stimulation in the jaw and femur of rats treated with bisphosphonate. Since the major toxicity factor of Gram-negative bacteria is lipopolysaccharide (LPS), the present study aimed to evaluate the relationship between osteonecrosis and LPS in a rat model of BRON-like lesions. Seventeen male rats were injected subcutaneously with zoledronic acid weekly for 4 weeks and divided into three groups: LPS (LPS administered into the bone marrow of the mandible and femur) and LPS plus polymyxin B (PMB) and saline groups (given neutralized LPS with PMB or saline, respectively, using the same protocol). At 4 weeks after the procedure, harvested specimens were analyzed using histomorphology (n=5 from each group) and histochemistry (n=1 each from LPS and LPS plus PMB groups). There was a significantly wider area of osteonecrosis in the LPS group as compared to the saline and LPS plus PMB groups in both the mandible (P=0.030 and P=0.009, respectively) and femur (P=0.002 and P=0.020, respectively). Our results indicate that LPS stimulation is deeply involved in the development and promotion of BRON.
authors.affiliation: Department of Science of Physical Function, Division of Maxillofacial Surgery, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Sakaguchi
authors.affiliation: Department of Science of Physical Function, Division of Oral Medicine, Kyushu Dental University, Kitakyushu, Japan. Electronic address: r08kokuryo@fa.kyu-dent.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Kokuryo
authors.affiliation: Department of Science of Physical Function, Division of Oral Medicine, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsurushima
authors.affiliation: Department of Science of Physical Function, Division of Maxillofacial Surgery, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Department of Science of Physical Function, Division of Maxillofacial Surgery, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Habu
authors.affiliation: Department of Science of Physical Function, Division of Maxillofacial Surgery, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Uehara
authors.affiliation: Department of Health Promotion, Division of Infections and Molecular Biology, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishihara
authors.affiliation: Department of Science of Physical Function, Division of Maxillofacial Surgery, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology*; D004164:Diphosphonates / Q000633:toxicity*; D007093:Imidazoles / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D008070:Lipopolysaccharides; C036757:lipopolysaccharide B; D000077211:Zoledronic Acid
keywords: LPS; bisphosphonate; bisphosphonate-related osteonecrosis of the jaw (BRONJ); lipopolysaccharide; model; rat