The effects of ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on the proliferation and differentiation of stimulated periodontal ligament fibroblasts

Abstract

The effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on rat periodontal ligament (PDL) fibroblast and osteoblast population dynamics was measured following orthodontic stimulation of alveolar bone formation. When compared with controls, doses of 0.2 and 0.4 mg EHDP/kg/d had no significant effect on the cell population dynamics associated with orthodontically stimulated alveolar bone formation. However, the two highest doses, 2.0 and 10.0 mg EHDP/kg/d, caused significant decreases in PDL fibroblast proliferation and osteoblast generation. The nature of the changes in these periodontal cell populations was dose related. In rats treated with 2.0 mg/kg/d the magnitude of the reduced osteoblast generation (26%) was accounted for by decreased fibroblast proliferation (22%). The decrease in osteoblast generation in rats treated with 10 mg EHDP/kg/d involved both reduced fibroblast proliferation as well as an inhibitory effect on the differentiation of PDL fibroblasts into osteoblasts. Qualitatively, the amount of alveolar bone formation appeared reduced only in histological sections from those rats treated with 10 mg EHDP/kg/d. These results indicate a dose related effect of EHDP on the cell population dynamics associated with orthodontically stimulated alveolar bone formation. At sufficiently high doses, EHDP decreases generation of osteoblasts which in turn results in reduced alveolar bone formation.