The long-term skeletal effects of EHDP in dogs.

Disodium hydroxymethanediphosphonic acid was administered subcutaneously (s.c.) to adult beagle dogs for 1 to 2 years at various dose levels to determine its skeletal effects when given chronically. The effects were followed densitometrically, radiographically and by making histomorphometric measurements in sequential rib biopsies. At low doses (0.1 and 0.5 mg/kg/day s.c.) EHDP caused a time-and-dose dependent reduction in the percentage of bone surfaces with active mineralization, a reduction in mineralization rates, a reduction in resorption spaces but no changes in osteoid seam widths. No treatment related bone fractures were noted at the 0.1 mg/kg/day level, while at 0.5 mg/kg/day, fracture incidence appeared slightly increased. At higher doses (2-10 mg/kg/day), there was also a reduction in the number of resorption spaces, but mineralization activity was totally blocked, osteoid seams became thickened and fracture incidence was markedly increased. In one group of animals, EHDP treatment was discontinued after one year of dosage at 5 mg/kg/day given subcutaneously. In these animals, mineralization activity reappeared within 3 months, but osteoid seams remained thickened until 7 months post-treatment. These data indicate that EHDP can have profound effects on bone remodeling in the dog but that these effects are dose-and-time-dependent and they appear to be reversible.

Effect of ethane-1-hydroxy-1,1-diphosphonate and vitamin D on bone mineralization.

Administration of large quantities of ethane-1-hydroxy-1,1-diphosphonate to growing chicks resulted in a decrease in percent bone ash and an increase in percent osteoid. The degree of inhibition of bone mineral accumulation was a function of both duration and quantity of ethane-1-hydroxy-1,1-diphosphonic acid administration. The inhibition of bone mineral accumulation could be partially corrected with administration of 1,25-dihydroxyvitamin D3. Administration of high levels of ethane-1-hydroxy-1,1-diphosphonate also resulted in inhibition of intestinal calcium absorption. This could be reversed or prevented by the administration of 1,25-dihydroxyvitamin D3.

Technic for serial bone sampling in canine skeletal labeling studies.

A technic was described for repetitive bone sampling in beagle dogs. The procedure has provided ideal samples for quantitative histologic technics following 135 biopsies.