Effects of alendronate on bone remodeling around osseointegrated implants in rats

Abstract

Purpose: Since the first report about BRONJ (bisphosphonate-related osteonecrosis of the jaw) in 2003, many reports have been issued. Recently, bisphosphonate-associated late failures of dental implants have been reported. There are still fewer reports about peri-implant bone remodeling associated with bisphosphonates. The purpose of this study is to evaluate the chronological effects of alendronates on peri-implant bone remodeling in rats. Materials & Methods: Thirty-six Sprague-Dawley rats (body weight 130-140g, 4 weeks old, male) were first divided into the bisphosphonate and control groups. Then, they were again divided into 4-week, 8-week, and 12-week groups according to the period of subcutaneous administration. The maxillary first molars in each rat were extracted. At 1 month after the extraction, custom-made implants were inserted bilaterally into the extraction sites. After the 4-week-long period of osseointegration, the rats started to get subcutaneous injection of alendronate or saline for the predetermined periods of time. Then, the rats were euthanized. The specimens were prepared for histologic and micro-computed tomographic analyses. The s-CTX and s-OC levels of the 12-week groups were measured 4 times on a regular basis. Results: The empty lacunae in the 4-week bisphosphonate group outnumbered those in the 4-week control group significantly. No significant differences were found in the TRAP-positive cell counts, BV / TV data, and BMD data among the control and bisphosphonate groups. The s-CTX levels of the bisphosphonate group declined with time without significance, and those of the control group also declined significantly. The difference of s-OC levels between the control and bisphosphonate groups at +8 weeks was significant. The median values of s-OC in the bisphosphonate group were continuously lower than those in the control group at each time of blood sampling.Conclusion: Within the limitations of this study, there were no consistent results among the histologic, micro-computed tomographic and biochemical data regarding the peri-implant bone remodeling associated with alendronate. At some specific points of time, the reduction of osteoclastic and osteoblastic functions was observed. An s-OC measurement is seen as a more reliable test tool for bisphosphonate effects. In summary, alendronate seems to have affected the bone remodeling around osseointegrated implants.