The Effect of Etidronate on Alveolar Bone Remodeling in Dog Mandible

Abstract

Etidronate belongs to a class of drugs called bisphosphonates, which are prescribed for the treatment of osteoporosis and other metabolic bone diseases. The main effect of these drugs is to inhibit bone resorption and, thereby, bone remodeling (coupled bone turnover). Extensive research has been done to study the effects of these drugs on the adult skeleton, but no study has quantified the effects of bisphosphonates on different regions of the mandible or compared the effects on alveolar bone remodeling with another cortical site. The purpose of the project was to histomorphometrically quantify the effects of etidronate therapy on the alveolar bone of the mandible and to determine if this site is affected differently than the cortical bone in the rib. The hypotheses were as follows: Etidronate therapy inhibits rib and mandibular cortical bone remodeling. Etidronate has a greater effect on remodeling inhibition in sites (alveolar vs. rib) with normally higher remodeling activity. High doses of etidronate impair normal mineralization of alveolar and rib cortical bone. Specimens from eight mature female dogs were obtained from an ongoing experiment on bisphosphonates. The dogs were randomly assigned to either a control group, a high dose experimental group (5.0 mg/kg/day), or a low dose experimental group (0.5 mg/kg/day). Drug treatment time was seven months. To quantify regional bone remodeling, intravitally labeled ribs and mandibles were analyzed using stereological point-hit and linear intercept methods to determine bone formation rate (BFR) and mineral apposition rate (MAR). Alveolar bone was analyzed by region (coronal, middle, and basal). We found extensive variability in our data which was most likely due to the small number of specimens, and the small amount of tissue in each specimen. Results show that as drug dosage increases MAR and BFR tend to decrease. In the high dose groups remodeling is turned off completely. This trend is seen in both mandible and rib. In the control animals, the highest remodeling rates were seen in the coronal region. Remodeling in the coronal region was not significantly different than the rib. The percent change in MAR and BFR from control to the low dose group is greatest in the coronal region of the mandible. Bone volume appears to not be affected by drug treatment. Although osteoid volume and cortical osteoid surface changes were not statistically significant, trabecular osteoid surface did demonstrate a dose dependent increase. The data suggest that bone remodeling in the rib and mandible decreases with etidronate therapy to the extent that with the high dose etidronate therapy remodeling appears to be shut off. Also, etidronate appears to have a greater affect on bone that has higher turnover rates. Aside from the regional differences in the mandible, the rib does not appear to be affected differently than the mandible.