An osteonecrosis model induced by oral bisphosphonate in ovariectomised rats.
OBJECTIVE
To develop a model of osteonecrosis using oral bisphosphonate in ovariectomy-induced osteoporotic rats.


METHODS
Thirty-six rats were subjected to ovariectomy or sham surgery. After 8 weeks, rats received oral alendronate (1.0 mg kg(-1) ) or saline once weekly for 4 weeks; then, serum C-telopeptide cross-linked collagen type I levels were measured to evaluate bone metabolism. Twelve rats from each group were injected with either lipopolysaccharide or saline into the bone marrow of the mandibles and femurs, and the areas of osteonecrosis were evaluated by histomorphometry.


RESULTS
Serum C-telopeptide cross-linked collagen type I levels were significantly increased in the ovariectomy group (105.1 ± 2.1 ng ml(-1) ) compared with the sham group (78.9 ± 12.5 ng ml(-1) ); they were significantly reduced following oral alendronate administration in the ovariectomy group (91.0 ± 4.4 ng ml(-1) ). Following alendronate and lipopolysaccharide administration, extensive osteonecrosis was observed in the mandibles and femurs of ovariectomy (0.45 ± 0.08 mm(2) , 1.69 ± 0.72 mm(2) , respectively) and sham (1.12 ± 0.45 mm(2) , 1.84 ± 0.66 mm(2) , respectively) groups. Significantly wider osteonecrosis occurred in the mandibles of sham-operated rats than ovariectomy rats following alendronate or lipopolysaccharide treatment.


CONCLUSIONS
We successfully developed a model of osteonecrosis in ovariectomised rats following oral bisphosphonate administration.
Division of Oral Medicine, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Japan.
J
J
Tanaka
Division of Oral Medicine, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Japan.
S
S
Kokuryo
Division of Maxillofacial Surgery, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Japan.
D
D
Yoshiga
Division of Oral Medicine, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Japan.
H
H
Tsurushima
Division of Oral Medicine, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Japan.
O
O
Sakaguchi
Division of Maxillofacial Surgery, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Japan.
M
M
Habu
Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Japan.
T
T
Nishihara
Division of Oral Medicine, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Japan.
I
I
Yoshioka
Division of Maxillofacial Surgery, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Japan.
K
K
Tominaga
D000284:Administration, Oral; D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D007267:Injections; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008334:Mandible; D010020:Osteonecrosis / Q000139:chemically induced*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar
D050071:Bone Density Conservation Agents; D008070:Lipopolysaccharides; D019386:Alendronate
alendronate; bisphosphonate-related osteonecrosis of the jaw; oral bisphosphonate; ovariectomy; rat