Effects of the Phosphodiesterase-5 (PDE-5) Inhibitors, Avanafil and Zaprinast, on Bone Remodeling and Oxidative Damage in a Rat Model of Glucocorticoid-Induced Osteoporosis

Background: The aim of this study was to evaluate the effects of the phosphodiesterase-5 (PDE-5) inhibitors, zaprinast and avanafil, on NO signalling pathway, bone mineral density (BMD), epiphyseal bone width, bone marrow angiogenesis, and parameters of oxidative stress in a rat model of glucocorticoid-induced osteoporosis (GIOP). Material/Methods: Twenty-four 8-month-old male rats in four groups were given a single daily treatment during a 30-day period: an (untreated) control group (n= 6): a dexamethasone-treated group (120 mu/kg) (n= 6); a group treated with dexamethasone (120 mu/kg) and zaprinast (10 mg/kg) (n= 6): and a group treated with dexamethasone (120 mu/kg) and avanafil (10 mg/kg) (n= 6). Rat whole body bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA), and bone histology was performed. Also, selected oxidative stress parameters by HPLC method and the other biochemical parameters by ELISA method were measured. Results: The GIOP model rats treated with zaprinast and avanafil showed a significant increase in NO, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) (NO/cGMP/PKG) signaling-pathway components, and in C-terminal telopeptide of type I collagen (CTX-1), bone marrow angiogenesis, BMD, and epiphyseal bone width, compared with the (untreated) control rats (p<0.05). Levels of pyridinoline (PD) and deoxypyridinoline (DPD) were significantly reduced in the dexamethasone + zaprinast, and dexamethasone + avanafil treatment groups (p< 0.05). Malondialdehyde (MDA), ubiquinone-10 (CoQ10), ubiquinol CoQ10 (CoQ10H), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were significantly increased in the dexamethasone-treated group, compared with the (untreated) controls (p< 0.05). Conclusions: In the GIOP rat model, markers of oxidative stress and bone atrophy were significantly reduced by treatment with the PDE-5 inhibitors, zaprinast and avanafil.