A inibição da fosfodiesterase-5 (PDE5) melhora a regeneração óssea nos estágios precoces da necrose avascular traumática da cabeça do fêmur em ratos

Abstract

Post-traumatic avascular necrosis of the femoral head (ANFH) affects young patients 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 (PDE5) 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 ischemic bone. The author's hypothesis is that PDE5 inhibitors work by promoting bone tissue regeneration through neoangiogenic and osteogenic actions. Thirty male SD rats (6-month-old) were subjected to an experimental model of traumatic ANFH, divided into 2 groups, according to the administration of 5 mg/kg sildenafil citrate or water (control group). Rats were then sacrificed at 7, 14, and 21 days. Histological (H&E, blue toluidine, Goldner's trichrome), histochemical (periodic acid-Schiff [PAS]) and immunohistochemical (VEGF and osteopontin) techniques were used to quantify bone and vascular responses. Higher levels of VEGF (p<0.01) and osteopontin (p<0.01) immunostaining in the epiphysis, increased VEGF immunostaining in the epiphyseal growth plate (p <0.01), 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 citrate-treated group. The present study demonstrated that sildenafil citrate optimized bone tissue regeneration by increasing VEGF signaling and osteopontin expression, with increased bone formation (osteoid and carbohydrate macromolecule deposition) in the early stages following traumatic ischemic insult. Thus, sildenafil citrate treatment may improve the prognosis of patients with osteonecrosis.