Effects of alendronate in relation to the administration period on bone metabolism around implants in rats

Abstract

Alendronate belongs to the bisphosphonate class of drugs that has been widely prescribed to prevent or treat various bone disorders. Its increased clinical application has raised concerns about complications such as failure of implant osseointegration and medication-related osteonecrosis of the jaw (MRONJ) in dentistry. A few previous animal studies that have attempted to determine the effects of bisphosphonates on the bone around the implant area were performed on sites other than jaw bones or used bisphosphonates other than alendronate. The present study aimed to determine the effects of alendronate in relation to the administration period on bone metabolism around implants placed in the rat maxilla from a multidisciplinary point of view, by employing microcomputed tomographic, histologic, and biochemical analyses. Thirty-six male Sprague-Dawley rats received periodic subcutaneous injections of either alendronate (alendronate group, n=18) or normal saline (control group, n=18) 4 weeks after the extraction of the maxillary first molars. The custom-made titanium implants were placed bilaterally into the extraction sites 4 weeks after the commencement of injection protocol. The rats were sacrificed at either 4, 8, or 12 weeks after implantation (4-, 8-, and 12-week groups, respectively; n=6 rats per group). Microcomputed tomographic and histologic analyses were conducted for all rats. Biochemical analyses were additionally carried out at four time points for the 12-week groups. There were no statistically significant differences between the groups on microcomputed tomographic and histologic analyses. The measured biochemical parameters showed a tendency of decrease over time except for the serum osteocalcin (s-OC) level of the control group, with significant differences among some time points within each group. The serum osteocalcin (s-OC) level was significantly lower in the 12-week alendronate group than in the control group (p < 0.05). Within the limitations of the present study, alendronate administration did not cause significant differences at the bone–implant interface during the early phase after implantation. However, alendronate might have affected bone metabolism around the implants during the late phase of the experimental period. Further researches that address the long-term validation and clinical availability of the results are required.