Effects of deleting cannabinoid receptor-2 on mechanical and material properties of cortical and trabecular bone

Cnr2 is one of two cannabinoid receptors known to regulate bone metabolism. Here, we compared the whole bone properties of femora and tibiae from three-month-old Cnr2−/− mice with wild-type controls using a C57BL/6 background. Bending stiffness was measured by three-point bending. The elastic modulus, density and mineral content were measured using ultrasound, Archimedes’ principle and ashing. Micro-CT was used to measure the second moment of area, inner and outer perimeters of the cortical shaft and trabecular parameters. Deleting Cnr2 increased the bending stiffness by increasing the second moment of area. Bone from affected male mice had a greater modulus than controls, although no difference was observed in females. The fractional volume of trabecular bone was greater in Cnr2−/− females than controls, while no difference was seen in males. These data indicate that inactivating Cnr2 increases the amount of cortical bone in both males and females at 3 months of age, but the effect on trabecular bone is different in the two sexes. These findings extend previous studies looking only at trabecular bone and provide further support for the possible use of Cnr2 antagonists for improving bone properties that may be of value in the treatment of bone disorders.