We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of
nuclear factor κB ligand) monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice
were ovariectomized (OVX) or sham operated. Four weeks after OVX, they were assigned to 3 different groups
to receive anti-RANKL monoclonal antibody (Ab) alone (5 mg/kg single injection at 4 weeks after OVX, Ab
group), teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group), or mAb
plus teriparatide (Ab + PTH group). Mice were sacrificed 8 weeks after OVX. Bone mineral density (BMD) was
measured at the femur and lumbar spine. Hind limbs were subjected to histological and histomorphometric analysis.
Serum osteocalcin and CTX-I levels were measured to investigate the bone turnover. Compared with Ab group,
Ab + PTH group showed a significant increase in BMD at distal femur and femoral shaft. Cortical bone volume was
significantly increased in PTH and Ab + PTH groups compared with Ab group. Bone turnover in Ab + PTH group
was suppressed to the same degree as in Ab group. The number of TRAP-positive multinucleated cells was markedly
reduced in Ab and Ab + PTH groups. These results suggest that combined treatment of teriparatide with
anti-RANKL antibody has additive effects on BMD in OVX mice compared with individual treatment.