Glycemic Fluctuation Aggravates Peri-implant Bone Loss in Diabetic Mice

Objectives: Hyperglycemia has been associated with peri-implant tissue damage in diabetic patients. The objective of this study is to examine the effect of glycemic fluctuation on experimental peri-implantitis in diabetic mice.
Methods: Maxillary left first and second molars of db/db mice were extracted and then dental implants were placed at healed site 6 weeks after extraction. After 4 weeks, rosiglitazone was given orally either regularly for glycemic control, or intermittently to induce glycemic fluctuation. Peri-implantitis was induced by tying ligatures around implants. After eight-week of treatment, bone loss around the implants was detected using micro-CT, and inflammatory infiltrate and osteoclastogenesis in peri-implant tissues were examined using HE staining and TRAP staining, respectively. Expressions of inflammatory cytokines and TLR signaling molecules in peri-implant tissues were measured using qRT-PCR. Oral bacteria were isolated from saliva before and after treatment, and bacterial composition was analyzed using 16s rRNA sequencing.
Results: Bone loss, inflammatory infiltrate and TRAP+ cell numbers were greater in mice with uncontrolled glycemia than those with controlled glycemia (p<0.05). However, mice with glycemic fluctuation demonstrated higher levels of bone loss, inflammatory infiltrate and TRAP+ cell formation than those with uncontrolled glycemia (p<0.05). Mice with glycemic fluctuation showed an increase in the mRNA expression of IL-1β, TNF-α, RANKL/OPG ratio as compared to mice with uncontrolled or controlled glycemia (p<0.05). Mice with glycemic fluctuation also exhibited significant elevated mRNA levels of TLR2/4, IRAK1 and TRAF6, compared to those with uncontrolled or controlled glycemia (p<0.05). A significant shift in the oral bacterial composition was observed in well or poor glycemic control groups, but the shift was independent of glycemic control or fluctuation.
Conclusions: Blood glucose fluctuation can aggravate peri-implantitis inflammation and bone loss, and it may be associated with the activation of TLR2/4-IRAK1-TRAF6 signaling, but not related to the shift in oral bacterial composition.