Combination of PTH (1-34) with anti-IL17 prevents bone loss by inhibiting IL-17/N-cadherin mediated disruption of PTHR1/LRP-6 interaction.

Combinations of anabolic and anti-resorptive agents have potential to improve bone density more than either agent alone. In this study, we determine the combining effect of anti-IL17 antibody and PTH (1-34) in mitigation of ovariectomy induced bone loss. Ovariectomized BALB/c female mice were treated with anti-IL17 and iPTH monotherapies and their combination. Combination of iPTH and anti-IL17 has synergistic effect in the restoration of skeletal and immune parameters compared to mono-therapies. Immunofluorescence analysis shows decreased expression of PTHR1 in iPTH+anti-IL17 treated bone sections. Our studies show that IL-17 up regulates N-cadherin which disrupts PTHR1/LRP-6 interaction thereby inhibiting wnt signaling and promoting bone loss. Our studies advocate use of iPTH and anti-IL17 combination therapy for post-menopausal osteoporosis.