【Animal modeling】-Effect of thalidomide on bisphosphonate-related osteonecrosis of the jaw

  Objective: To study the effect of thalidomide on bisphosphonate-related osteonecrosis of the jaw.

  METHODS: Thirty-six rats were randomly divided into groups A, B, and C, and received normal saline, zoledronic acid, zoledronic acid + thalidomide treatment, respectively. After 3 weeks of administration, the left maxillary first molars of the rats were extracted. Four and eight weeks after tooth extraction, the specimens were harvested and evaluated for osteonecrosis of the jaw, microangiogenesis and apoptosis.

  RESULTS: At 4 and 8 weeks after tooth extraction, no sequestrum was exposed at the extraction wounds of the maxillary bone of the rats, but some small fistulas were seen in some specimens of groups B and C. Histological examination showed that no sequestrum was found in the specimens of group A, while small sequestrum were seen around the extraction socket in groups B and C. The percentage of empty bone lacuna and the area of dead bone around the extraction socket in groups B and C were significantly higher than those in group A (P<0.01), while the density of bone lacuna decreased significantly. Compared with group A, the microvessel density of group B and group C also decreased significantly, by 25.87% and 55.27% at 4 weeks (P<0.01), and by 45.62% and 72.84% at 8 weeks (P<0.01) The number of apoptotic cells increased by 54.80% and 87.89% (P<0.01) at 4 weeks, and 208.08% and 250.58% at 8 weeks (P<0.01).

  Conclusion: Thalidomide aggravates zoledronic acid-induced osteonecrosis of the jaw in the early stage; the effects of thalidomide and zoledronic acid on osteonecrosis of the jaw are related to the inhibition of microangiogenesis.