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Phosphodiesterase‐5 inhibition improves bone regeneration at the early stages of ischemic osteonecrosis of the femoral head in rats

Posttraumatic osteonecrosis of the femoral head (ONFH) affects patients at different ages and may lead to functional limitation and joint replacement, with total hip arthroplasty, which is a costly procedure. Proposed methods to optimize ischemic tissue regeneration have been reported. Phosphodiesterase‐5 inhibitors act by inhibiting the degradation of guanosine 3′,5′‐cyclic monophosphate in the nitric oxide pathway, increasing its bioavailability and promoting vascular endothelial growth factor (VEGF)‐mediated neovascular recruitment and the induction of tissue regeneration in the traumatized bone. Thirty male Sprague–Dawley rats (6 months old) were subjected to an experimental model of traumatic ONFH divided into two groups, according to the administration of 5 mg/kg sildenafil or water (control group). Rats were then killed at 7, 14, and 21 days. Histological (Goldner's trichrome), histochemical (periodic acid–Schiff [PAS]), and immunohistochemical (VEGF and osteopontin [OPN]) techniques were used to quantify bone and vascular responses. Higher levels of VEGF (p < 0.01) and OPN (p < 0.01) immunostaining in the epiphysis, the greater formation of osteoid tissue (p < 0.01 on Day 7; p < 0.05 on Day 14), and higher levels of PAS staining (p < 0.01 on Day 7) were observed in the sildenafil‐treated group. The present study demonstrated that sildenafil optimized bone tissue regeneration by increasing VEGF signaling and OPN expression, with increased bone formation (osteoid and carbohydrate macromolecule deposition) in the early stages following traumatic ischemic insult. Thus, sildenafil treatment may improve the prognosis of patients with osteonecrosis.