Advanced glycation endproducts and rat dental implant osseointegration

Advanced glycation endproducts (AGEs) are a diverse group of molecular adducts formed in environments high in reducing sugars that accumulate with aging and in diabetes. This study tests the hypothesis that AGEs inhibit the stabile osseointegration of dental implants through tissue interactions that interfere with bone turnover and compromise the biomechanical properties at the bone-implant interface. Maxillary first molars were extracted from 32 rats and allowed to heal for 4 weeks. Titanium implants (1 mm x 3 mm) were placed in the healed sockets of 2 groups of 16 rats consisting of 8 rats injected 3 times/wk for 1 month with AGE (prepared from glucose and lysine) and 8 rats injected with vehicle as a control. AGE injections continued for an additional 14 or 28 days before sacrifice. X-ray images, blood, and tissues were collected to examine bone/implant contact ratio, serum pyridinoline ([PYD] a collagen breakdown marker), osteocalcin ([OSC] a bone formation marker), and for immunohistochemistry with antibodies to AGE and the bone turnover-marker protein matrix metalloproteinase1. Compared with the AGE-treated groups, the controls showed significantly higher bone/implant contact at both 14- and 28-day time points. PYD (P < .05) and OSC (trend) levels from controls showed decreases at 28 days when compared with AGE-treated groups. Immunohistochemistry with AGE-specific and bone turnover marker antibodies showed stronger staining associated with the implant/tissue interface in AGE-treated rats. Our studies indicate an association between AGE and inhibition of bone turnover, suggesting that the formation of AGE in high glycemic conditions, such as diabetes, may contribute to a slower rate of osseointegration that negatively affects implant stability.