Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

Abstract

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.

Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice

“…Similarly, the administration of anti-RANKL or anti-DKK1 to ovx mice showed significantly increased femur and lumbar spine BMD [36,37]. Treatment of ovx mice with anti-RANKL antibody resulted in decreased TRAP staining of the distal femur [37]. Our histomorphometric data demonstrate that the mode of action of MAb DLK1 in protecting bone loss is primarily mediated by reducing bone resorption as shown by significant reduction in the OC number in the proximal tibia of ovx mice injected with MAb DLK1.…”

“…Administration of selected MAb DLK1 to ovx mice resulted in increased total BMD and trabecular BV/TV. Similarly, the administration of anti-RANKL or anti-DKK1 to ovx mice showed significantly increased femur and lumbar spine BMD [36,37]. Treatment of ovx mice with anti-RANKL antibody resulted in decreased TRAP staining of the distal femur [37].…”

Exosomal miR-365a-5p derived from HUC-MSCs regulates osteogenesis in GIONFH through the Hippo signaling pathway

“…Several studies have reported the role played by GCs in the balance between osteogenesis and osteoclast formation in GIONFH. 20 , 21 However, BMSCs are the most important cells for bone regeneration. Xie et al.…”

Recent advances in the pharmaceutical manipulation of bone remodelling: the quest for a healthy skeleton

“…Combined treatment with teriparatide and BP does not provide an added beneficial influence on bone mineral densities although a combination with denosumab may have added benefits compared to an individual treatment regimen. 36 In rats, teriparatide causes an increase in the incidence of osteosarcoma in doses ranging from 3 to 60 times the exposure in humans. Patients with Paget's disease of bone, paediatric populations with open epiphyses and those receiving radiation therapy should not receive teriparatide due to the increased baseline risk of osteosarcoma.…”