Effects of osteoporosis and drugs on bone biomechanics.

Abstract

16 New Zealand White (NZW) rabbits were ovariectomised (OVX) and 20 left intact as age-matched controls. 4 controls were killed at time 0, then 4 from each group at 1,3,6 and 12 months post-OVX. Serum oestradiol and body weight were recorded. Post-mortem of the OVX animals confirmed that all ovarian tissue had been removed. Femoral and humeral diaphyses were tested in 4-point bending, metatarsals in torsion and cancellous bone from the femora and humeri in compression. Oestradiol levels were not altered by OVX and there were no significant reductions in strength, stiffness or density of cancellous or cortical bone 12 months post-OVX, except that OVX femoral strength was significantly lower than control strength (p < 0.05). In conclusion, the species was not a suitable model for post-menopausal osteoporosis. Due to the failure of the rabbit model, it was necessary to revert to the rat model of post-menopausal osteoporosis. Two mechanical tests were used to investigate the efficacy of an anti-resorptive therapy (Oestradiol-3-benzoate) and an anabolic therapy (Parathyroid Hormone). An indentation test examined the properties of cancellous bone material, while the femoral neck bending test examined the properties of the bone as an organ by reproducing the in vivo events leading to a shear fracture of the hip. Biomechanical variables were related to Bone Mineral Density, a measure of bone mass currently in use in clinical practice, by scanning the bones using peripheral quantitative computed tomography (pQCT) before mechanical testing took place. It was found that cancellous bone density and indentation strength decreased and cortical bone density increased 6 weeks post-OVX: high levels of oestradiol-3- benzoate prevented these changes . Total bone mineral density was strongly correlated with indentation strength (r=0.92). Parathyroid hormone did not restore cancellous bone density of OVX to sham levels but restored biomechanical strength.