Methods: Diabetes was induced in adult male rats by streptozotocin injection. Non- diabetic rats served as controls. Four different CMCs, 2.5, 2.14, 2.23, 2.24, were administered by oral gavage (100mg/kg) daily. Untreated diabetics received vehicle alone. After three weeks, the rats were sacrificed and gingiva, skin, bone and blood samples collected. The maxillary jaws were dissected and x-rayed using an internal step wedge for bone density measurements. Blood samples were analyzed for bone biomarkers, including osteocalcin, bone-specific-alkaline phosphatase, tartrate-resistant acid phosphatase, and C-telopeptide of type I collagen (CTX).
Results: In experiment I, diabetes increased interproximal alveolar bone loss (site7) by 25% and CMC 2.5 decreased the excessive bone loss by 51% (P = 0.028). In experiment II, diabetes increased alveolar bone loss by 34.2% (P = 0.022). Of the three compounds tested (CMCs 2.14, 2.23, 2.24), only the latter reduced bone loss to near-normal values, and when scored clinically (0-3) the bone loss was significantly lower than untreated diabetics (P= 0.036). Diabetes also appears to reduce bone density in the tibia (P = 0.004) but the effect of the compounds is still being determined. In addition, blood samples are being analyzed for bone biomarkers and preliminary results indicate a dramatic reduction in serum osteocalcin in diabetics verses non-diabetics.
Conclusion: Of the four compounds tested, only two CMCs(2.5, 2.24) appear effective in reducing alveolar bone loss in diabetic rats. Of interest, these two compounds are also effective inhibitors of matrix metalloproteinases in vitro and cytokine production in cell culture and may be therapeutically effective in periodontal disease.
Supported by NYSTAR (#A43273), The center for Advanced Biotech, Stony Brook University, and Chem Master Intl.