Biomechanical effects of the full range of useful doses of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) on femur diaphyses and cortical bone tissue in rats.

The effects of i.p. doses of 0.016, 0.16, 1.6, 5, 16, 50 and 160 microM/kg/day of APD, over a period of 23 days, on geometric and biomechanical properties of femoral diaphyses in bending were determined in groups of seven growing rats. Both elastic and ultimate strength increased with low doses and decreased with high doses. Geometric (mass) variables (diaphyseal volume, wall/lumen ratio) correlated positively, and material properties (limit elastic stress, modulus of elasticity) negatively, with log dose. Normal mass and improved quality at low doses, and improved mass and impaired quality data at high doses were obtained. No changes in sectional moment of inertia (Ix, an expression of bone architecture) were observed. Biphasic changes in diaphyseal strength expressed the effects of APD on material quality in spite of mass variation. The contrasting lack of changes in Ix may have reflected the blocking effect of APD on osteoclast-osteoblast communication, essential for directional modulation of remodelling.