Bone density and shape as determinants of bone strength in IGF-I and/or pamidronate-treated ovariectomized rats

Areal bone mineral density (BMD) is a major determinant of bone strength and thereby of fracture risk. Other factors including trabecular microarchitecture and bone dimensions also contribute to bone strength. To investigate the relative importance for bone strength of BMD and bone dimensions, the relations between strength and the latter variables were evaluated under different experimental conditions in ovariectomized rats. Bone strength was assessed in compression and bending with measurement of BMD by dual-energy X-ray absorptiometry. Interventions were designed to increase trabecular BMD in rats with estrogen deficiency-induced bone loss (OVX) by treatment with pamidronate, an inhibitor of bone resorption, or to modify bone dimensions, particularly diameter, by administration of the growth factor IGF-I. In OVX rats, pamidronate treatment increased BMD with a commensurate increase in bone strength at the level of lumbar vertebrae and femoral neck (r = 0.789, p < 0.0001 and r = 0.535, p < 0.001, respectively). IGF-I increased the external diameter of midshaft tibia and femoral neck, which also correlated with bone strength (r = 0.678,p < 0.0001 and r = 0.507,p < 0.0002, respectively). Thus, both bone dimensions and BMD contributed to the determination of bone strength. In conclusion, adult rats with estrogen deficiency-induced bone loss represent a useful experimental model for investigating bone strength and its determinants such as BMD and external bone dimensions.