Sildenafil Transiently Delays Early Alveolar Healing of Tooth Extraction Sockets

Bone is a unique tissue that has the ability to repair itself and return to full function. Bone regeneration is a well synchronized biological process that recapitulates embryonic bone development. The establishment of a functional vascular supply has been shown to be essential for proper ossification of newly deposited bone, and impaired angiogenesis as in advanced age, diabetes, and anti-cancer treatments affect bone repair. Endothelial Guanosine, 3′, 5′-Cyclic Monophophate(cGMP) is known to support angiogenesis, and sildenafil, a Phosphodiesterase 5 (PDE5) antagonist, prevents cGMP hydrolysis and thereby, promotes the formation of new blood vessels. Since the development of functional vascular networks is critical to bone repair, we investigated the effects of sildenafil on early alveolar bone regeneration following exodontia. Our results demonstrate that per-oral administration of sildenafil (10 mg/kg/day) in rats delays the dissolution and replacement of the sanguine clot with granulation tissue. As a result, the number of replicating cells, a hallmark of regenerating tissue, observed on day 4 was remarkably lower in sildenafil-treated animals than their control counterparts (mean±SD; control: 47.35±9.21; sildenafil: 11.47±5.14). Similarly, cells expressing transcription factor Cbfa-1/Runx2 and osteopontin, markers of differentiating osteoblasts, were fewer in treated animals (mean±SD; control: 83.18 ± 4.60; sildenafil: 13.77 ± 4.63). Treatment with hydrolysis-resistant cyclic GMP (cGMP) showed findings similar to sildenafil-treated animals suggesting a negative impact of cGMP on early inflammatory phase of bone healing. However, histological differences were not significant between the 2 groups on day 8. Based on these findings, we conclude that sildenafil temporarily retards early events in alveolar bone healing.