The effects of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on mineral and organic components of rat bone

Abstract

The purpose of this study was to determine the short-term effects of various systemic doses of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on bone organic matrix and to relate these effects to the corresponding dose-related changes in bone mineral. EHDP was administered daily by subcutaneous injection at doses of 0.25, 2.5 and 40 mg/kg body weight for periods of one and two weeks. At both time intervals, rat tibiae were quantitatively analyzed for mineral content (ash, calcium and phosphorus) and for organic matrix content (matrix weight, nitrogen and certain amino acids). The latter data were correlated with semiquantitative histological analyses of the tibiae. Results of this study demonstrate that the short term effects of EHDP on bone chemistry and histology are variable and depend on the systemic dose and the duration of treatment. Systemic doses of 0.25 and 2.5 mg/kg EHDP following daily administration for one week resulted in transitory decreases in bone mineral content compared to controls. Following two weeks of treatment, both of these dose levels resulted in increased bone mineral content and, in addition, the 2.5 mg/kg dose resulted in tibiae which contained more organic matrix compared to control bones. In contrast to the low dose effects, a high systemic dose of EHDP—e.g. 40 mg/kg administered daily for 1 or 2 weeks—appears to act solely by inhibiting mineralization of newly-formed matrix.