Abstract: 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. Conclusion 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.