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 μ/kg) (n=6); a group treated with dexamethasone (120 μ/kg) and zaprinast (10 mg/kg) (n=6): and a group treated with dexamethasone (120 μ/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.