Bisphosphonate (pamidronate/APD) prevents arthritis-induced loss of fracture toughness in the rabbit femoral diaphysis.
Patients with rheumatoid and other inflammatory arthritis have an increased risk for fracture. This study was designed to determine the effect of experimental inflammatory arthritis on the material properties (fracture toughness and shear modulus) and structural properties (torque, angular deflection, and absorbed energy) of femoral diaphyseal bone tested in torsion to fracture, as well as the effect on these properties of APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate), a drug known to block osteoclast activity. Two dose levels were investigated. Experimental inflammatory arthritis was induced by intra-articular injection 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 diaphyses of each excised right femur were loaded to fracture in torsion at an angular deflection rate of 8 degrees/sec. In the arthritis group, the fracture toughness was 39% lower than in the normal group, and the structural properties all were reduced significantly. By contrast, the shear modulus was unaffected by arthritis. In this study, the higher dose level (0.3 mg/kg of body weight) of APD prevented loss of fracture toughness and maintained the structural properties in experimental inflammatory arthritis; the low dose was not effective.
Wellesley Hospital Orthopaedic Research Laboratory, Toronto, Ontario, Canada.
C M
CM
Bellingham
J M
JM
Lee
E L
EL
Moran
E R
ER
Bogoch
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control*; D002351:Carrageenan; D018483:Diaphyses / Q000187:drug effects / Q000503:physiopathology; D004164:Diphosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D005260:Female; D006244:Hardness; D000077268:Pamidronate; D011817:Rabbits; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects* / Q000503:physiopathology; D013978:Tibial Fractures / Q000517:prevention & control; D016474:Weight-Bearing
D004164:Diphosphonates; D002351:Carrageenan; D000077268:Pamidronate