BISPHOSPHONATE (PAMIDRONATE APD) PREVENTS ARTHRITIS-INDUCED LOSS OF FRACTURE-TOUGHNESS IN THE RABBIT FEMORAL DIAPHYSIS

Patients with rheumatoid and other inflammatory arthritis have an incr eased risk for fracture. This study was designed to determine the effe ct of experimental inflammatory arthritis on the material properties ( fracture toughness and shear modulus) and structural properties (torqu e, angular deflection, and absorbed energy) of femoral diaphyseal bone tested in torsion to fracture, as well as the effect on these propert ies of APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate), a drug k nown to block osteoclast activity. Two dose levels were investigated. Experimental inflammatory arthritis was induced by intra-articular inj ection of carrageenan into the right tibiofemoral joint, given over 7 weeks, in three groups of animals. Simultaneously, daily subcutaneous injections of APD were given to three groups of rabbits. Five groups ( 12 animals each) were established: normal, arthritis, normal/high dose APD, arthritis/high dose APD, and arthritis/low dose APD. The diaphys es of each excised right femur were loaded to fracture in torsion at a n angular deflection rate of 8 degrees/sec. In the arthritis group, th e fracture toughness was 39% lower than in the normal group, and the s tructural properties all were reduced significantly. By contrast, the shear modulus was unaffected by arthritis. In this study, the higher d ose level (0.3 mg/kg of body weight) of APD prevented loss of fracture toughness and maintained the structural properties in experimental in flammatory arthritis; the low dose was not effective.