EFFECT OF DICHLOROMETHYLENE DIPHOSPHONATE, A PYROPHOSPHATE ANALOG, ON BONE AND BONE CELL STRUCTURE IN THE GROWING-RAT

Dichloromethylene diphosphonate (Cl2MDP) is a synthetic compound related in structure to PPi, but is resistant to enzymatic and chemical degradation and is a potent bone resorption inhibitor. Administration of 20 mg/kg per day of Cl2MDP for 10 days to growing rats markedly increased metaphyseal mineralized tissue mass due to slowed bone resorption. Resorption areas covering anorganic bone increased as viewed by scanning electron microscopy (SEM). Resorption pits, or Howship''s lacunae, in these resorption areas were smaller and less defined than those encountered in controls. The appearance of these large areas of poorly delineated resorption pits is probably due to an inhibition of bone resorption coupled with slowed bone formation. Cl2MDP administration to growing rats increased osteoclast number and size. Osteoclasts were examined by transmission electron microscopy (TEM). Ruffled borders and associated cytoplasmic vacuoles were generally less extensive in the Cl2MDP-treated osteoclasts than in controls, although clear zones were frequently seen. Examination of undecalcified light microscopic sections reveal that the area of bone being degraded by adjacent osteoclasts was generally much smaller in Cl2MDP-treated animals than in controls. Collaborating TEM observations of smaller, less-defined resorption pits, with the light microscopic observations of smaller bone areas being degraded by individual osteoclasts provide a morphological basis for the observed decreases in bone resorption following Cl2MDP administration.