[Effect of thalidomide on development of bisphosphonate-related osteonecrosis of the jaws in rats].
OBJECTIVE
To investigate the effect of thalidomide on the development of bisphosphonate-related osteonecrosis of the jaws (BRONJ).


METHODS
Thirty-six rats were randomly divided into groups A, B and C, and treated with saline, zoledronate and zoledronate plus thalidomide, respectively. Three weeks later, the left maxillary first molars of the rats were extracted. Four and eight weeks after tooth extraction, samples were harvested for evaluation of osteonecrosis of the jaws, microvessel density, and cell apoptosis.


RESULTS
At both of the time points, no exposed dead bone was observed at the extraction socket areas in the rats except for some small fistulas in groups B and C. Histological examination confirmed the absence of dead bone in group A, whereas small areas of dead bone were observed around the extraction socket in groups B and C. Compared with those in group A, the percentage of empty lacunae and the area of dead bone were significantly increased (P<0.01), whereas bone lacunae density was significantly decreased (P<0.01) in groups B and C at both time points. Microvessel density in groups B and C were also significantly decreased (P<0.01) by 25.87% and 55.27% at week 4, and by 45.62% and 72.84% at week 8, respectively; the apoptotic cells in groups B and C increased by 54.80% and 87.89% at week 4 (P<0.01), and by 208.08% and 250.58% at week 8 (P<0.01), respectively.


CONCLUSIONS
Thalidomide can aggravate zoledronate-induced early-stage BRONJ, and their osteonecrosis-inducing effect of the jaw may be attributed, at least partly, to the inhibition of angiogenesis.
Department of Oral and Maxillofacial Surgery, College of Stomatology, College of Basic Medicine, North China University of Science and Technology, Tangshan 063000, China. E-mail: songzhiqiang2010@163.com.
Zhiqiang
Z
Song
Wei
W
Dong
Lujia
L
Yin
Juanjuan
J
Liu
Hong
H
Sun
Mengchun
M
Qi
D000818:Animals; D017209:Apoptosis; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000473:pathology*; D015519:Bone Density; D004164:Diphosphonates; D004195:Disease Models, Animal; D007093:Imidazoles; D008963:Molar; D018919:Neovascularization, Physiologic; D051381:Rats; D013792:Thalidomide / Q000009:adverse effects*; D014081:Tooth Extraction; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D013792:Thalidomide; D000077211:Zoledronic Acid