Do avanafil and zaprinast exert positive effects on bone tissue via the nitric oxide/cyclic guanosine monophosphate/protein kinase-G signaling pathway in rats with ovariectomy-induced osteoporosis?

Phosphodiesterase-5 inhibitors (PDE-5Is) exert positive effects on bone healing and mineralization by activation the nitric oxide/cyclic guanosine monophosphate/protein kinase-G (NO/cGMP/PKG) signaling pathway. In this study, the effects of zaprinast and avanafil, two PDE-5Is, on the NO signaling pathway, estrogen levels, selected bone formation and destruction marker levels, whole-body bone mineral density (WB-BMD), right femur trabecular bone thickness (RF-TBT) and epiphyseal bone width, angiogenesis in the bone-marrow, and selected oxidative stress parameter levels were investigated in rats with ovariectomy-induced osteoporosis. Twenty four adult rats (8 months old) were equally divided into four groups. The first group was the sham operated group. Groups 2, 3 and 4 included ovariectomized rats. At six months after ovariectomy, the 3rd and 4th groups were administered 10 mg/kg zaprinast and avanafil daily as a single dose for 60 days, respectively. Increases in the activity of the NO/cGMP/PKG signalling-pathway, C-terminal collagen peptide levels, angiogenesis in the bone marrow, RF-TBT, epiphyseal bone width and WB-BMD were observed compared to the ovariectomized positive control group (OVX), while the pyridinoline and deoxypyridinoline levels were decreased in the OVX+zaprinast and OVX+avanafil groups (p