Bone Formation around Titanium Implants in Diabetic and Normal Rats

Diabetes Mellitus is currently recognised as a contraindication for implant treatment due to impaired osseointegration leading to early failure. The reason for the slower bone formation is unclear, but is related to poor glycaemic control in the post operative period. Objectives: To investigate osteoblast cellular activity around implant sites of normal and diabetic rats. Methods: Implants were inserted into both normal Wistar rats and GK diabetic rats immediately following incisor extraction. Rats were sacrificed at 1, 3 or 9 weeks post-operation. Dissected mandibles were fixed in formalin, demineralised in formic acid and paraffin embedded. 5 micron sections were taken from posterior and anterior aspects of the mandible and stained histologically using H&E or Alzarin red (mineral deposition). Immunohistochemistry was performed to investigate the presence of the osteoblast differentiation marker osteopontin, and proliferation marker, PCNA. Results: H&E staining revealed a cell rich granulation tissue around the implant site at 1 week in both animals. At 3 and 9 weeks, bone formation was more advanced in normal rats than diabetic rats, which was evident in both posterior and anterior sections. Alizarin red staining showed greater mineralisation in normal rats compared to diabetic animals. Osteopontin was observed around normal and diabetic implant sockets by 3 weeks. By 9 weeks osteopontin was no longer detected around the normal implant socket, while it persisted around the diabetic implant socket. PCNA expression was observed around normal and diabetic implant sockets at 1 and 3 weeks post-operation. Expression was absent around normal implant socket by 9 weeks but evident around the diabetic implant socket. Similar temporal patterns for bone markers were observed for anterior and posterior sections. Conclusions: Diabetes had a significant effect on cellular proliferation and osteoblast differentiation, which was particularly evident 9 weeks post operation. This had consequential effects on reduced bone formation around implants.