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At these doses, both drugs enhanced bone regeneration at the femur osteotomy site and completely restored bone mass, microarchitecture, and strength in OVX mice. Furthermore, both drugs increased surface referent bone formation and serum bone formation marker (P1NP) without affecting the resorption marker (CTX-1). Both drugs increased the expression of VEGF and VEGFR2 in bones and osteoblasts and increased skeletal vascularity. Sunitinib completely blocked the bone restorative and vascular effects of sildenafil and vardenafil in OVX mice.
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