Ranitidine Impairs Bone Healing and Implant Osseointegration in Rats' Tibiae

Abstract

Ranitidine has been found to have an impact on bone metabolism by suppressing osteoclastogenesis. We hypothesized that the use of ranitidine would impair bone healing and implant osseointegration. This study investigated the effect of postoperative administration of ranitidine on bone healing and osseointegration in rats. Twenty-two Sprague-Dawley rats underwent surgery to create a unicortical bone defect in each tibia. A titanium implant was placed on the right tibial defect, whereas the contralateral defect was left unfilled. After surgery, the rats were randomly divided into 2 groups receiving a daily dose of ranitidine or saline solution for 14days and then euthanized for assessment of bone healing and osseointegration using micro-computed tomography (CT) and histomorphometry. Micro-CT analysis of the bone defect showed a larger bone defect volume in the ranitidine group (0.82±0.13μL vs 0.66±0.16μL, P=.034), thinner cortical thickness (0.54±0.07mm vs 0.63±0.11mm, P=.026), and less bone regeneration at the defect site (40%±12% vs 57%±11%, P=.003).Implant-site micro-CT analysis showed less osseointegration in the ranitidine group (34.1%±2.7% vs 43.5%±2.1%, P=.014), and implant-site histologic analysis showed less medullary (P=.021), cortical (P=.001), and total (P=.003) bone-implant contact and less peri-implant bone volume-tissue volume (P=.002) in the ranitidine group. Histologic analysis for osteoclastic activity showed a lower number of osteoclasts in the ranitidine group (4.8±2.4mm-2 vs 9.1±2.1mm-2, P=.026). The postoperative use of ranitidine impaired bone healing and osseointegration.