COMPARISON OF THE DISTRIBUTION OF H-3 ALENDRONATE AND H-3 ETIDRONATE IN RAT AND MOUSE BONES

Alendronate and etidronate are bisphosphonates used clinically to trea t diseases associated with increased bone resorption, Etidronate is le ss potent and was reported to cause osteomalacia, This study examines if differences in distribution of alendronate and etidronate in the sk eleton can explain differences in efficacy and in effects on mineraliz ation between the two drugs, Eight-day old rat pups were injected s.c. with H-3-alendronate or H-3-etidronate both at either 1.3 mu mol/kg o r at their respective pharmacological effective doses in the growing r at of 0.12 mu mol/kg for alendronate and 72.8 mu mol/kg for etidronate , Twelve hours after administration, at 1.3 mu mol/kg both drugs showe d a three- to fourfold higher localization on osteoclast vs, osteoblas t surface, At the pharmacologically effective doses, H-3-alendronate l abeled eightfold more osteoclast surface than osteoblast surface, In c ontrast, H-3-etidronate labeled approximately equal fractions of osteo clast and osteoblast surface, When similar doses of H-3-etidronate and H-3-alendronate (0.24 mu mol/kg H-3-etidronate vs. 0.20 mu mol/kg H-3 -alendronate; 1.5 mu mol/kg H-3-etidronate vs. 1.2 mu mol/kg H-3-alend ronate; and 14.6 mu mol/kg H-3-etidronate vs. 12.0 mu mol/kg H-3-alend ronate) were injected intravenously into adult mice at similar specifi c activities, H-3-etidronate labeled 1.5-2.5 times more osteoclast sur face than H-3-alendronate, but 3 to 15 times more osteoblast surface, Consequently, the ratio between the fraction of labeled osteoclast sur face acid the fraction of labeled osteoblast surface ranged for H-3-al endronate from 9 to 24, whereas for H-3-etidronate the range was from 4 to 7, due to more extensive labeling of osteoblast surface by H-3-et idronate, In a third experiment, we confirmed in adult mice the previo us observation made in rat pups that normal bone formation occurs over alendronate-covered bone surfaces, and found that it occurred over et idronate-covered surfaces as well, Forty nine days after s.c. administ ration of alendronate at 0.12 mu mol/kg or etidronate at 1.3 mu mol/kg or 55.3 mu mol/kg into adult mice bone formed over drug label, The di stance from incorporated label to bone surface for both drugs (12.7 mu m for alendronate and 8.7 and 9.2 mu m for etidronate) was similar to wall width (defined by cement line) in controls (10.6 mu m), In concl usion, alendronate, especially at pharmacologically active doses, show s higher uptake on resorption vs. formation surfaces than etidronate, The extent of bone formation on surfaces containing alendronate or eti dronate is similar and is comparable to the ''wall width'' in controls .