The effect of switching from teriparatide to anti-RANKL antibody on cancellous and cortical bone in ovariectomized mice

We examined the effect of teriparatide, and switching from teriparatide to anti-RANKL (receptor activator of nuclear factor κB ligand) monoclonal antibody, in ovariectomized mice. Twelve-week-old female C57BL/6 mice were ovariectomized or sham operated. Four weeks after surgery, ovariectomized mice were subjected to one of the following four treatments: phosphate-buffered saline (PBS) for 8 weeks; teriparatide for 4 weeks followed by PBS for 4 weeks (PTH4W group); teriparatide for 8 weeks (PTH8W group); or teriparatide for 4 weeks followed by anti-RANKL antibody (single subcutaneous injection of 5 mg/kg) (SWITCH group). Twelve weeks after the operation, bone mineral density was increased in PTH8W and SWITCH groups to broadly comparable levels, but these were significantly decreased in the PTH4W group after discontinuation of teriparatide. Histomorphometric analysis demonstrated that cancellous bone formation and resorption were profoundly suppressed in the SWITCH group. Bone formation was also suppressed on the endocortical surface of cortical bone but was maintained on the periosteal surface. Anti-RANKL antibody suppressed osteoclast activity immediately after treatment, while bone formation was only gradually decreased. These results suggest that anti-RANKL antibody may be a therapeutic option after discontinuation of teriparatide therapy.