Host modulation therapy for improving the osseointegration of dental implants under bone healing-suppressed conditions: a preclinical rodent-model experiment

Abstract

Purpose: Placing dental implants in areas with low bone density or in conditions where bone healing is suppressed is challenging for clinicians. An experiment using a rodent model was performed with the aim of determining the efficacy of host modulation by increasing the systemic level of cholesterol sulfate (CS) using Irosustat in the context of the bone healing process around dental implants.

Methods: In 16 ovariectomised female Sprague-Dawley rats, 2 implant fixtures were placed in the tibial bones (1 fixture on each side). At 1 week after surgery, the high-CS group (n=8) received Irosustat-mixed feed, while the control group (n=8) was fed conventionally. Block specimens were obtained at 5 weeks post-surgery for histologic analysis and the data were evaluated statistically (P<0.05).

Results: Unlike the high-CS group, half of the specimens in the control group demonstrated severe bone resorption along with a periosteal reaction in the cortex. The mean percentages of bone-to-implant contact (21.5%) and bone density (28.1%) near the implant surface were significantly higher in the high-CS group than in the control group (P<0.05), as was the number of Haversian canals (by 5.3).

Conclusions: Host modulation by increasing the CS level may enhance the osseointegration of dental implants placed under conditions of impaired bone healing.

Keywords: Animal research; Bone; Dental implants; Osseointegration; Rodents.

Figure 1. Experimental materials. (A) Irosustat is an orally active non-steroidal inhibitor of steroid sulfatase that maintains a high level of systemic cholesterol sulfate. (B) Photograph (left) and blueprint (right) of the dental implant with a sandblasted, large-grit, acid-etched surface customised for rats.

Figure 2. Overall timeline of the experiment.

CS: cholesterol sulfate.

Figure 3. Clinical photographs and radiographs summarising the surgical procedure.

Figure 4. Results of the histomorphometric analysis. Within the ROI that was defined as the second to fifth threads from the fixture platform, percentage of bone-to-implant contact was measured as the proportion of the total length of bone tissue in contact with the implant fixture surface (yellow dotted lines) over the total length of the fixture surface (white dotted line). The interthread space was defined between an imaginary line that connected the tops of the fixture thread tips within the ROI (red dotted line) and the fixture outline (white dotted line). Within the 3 interthread spaces of the ROI, percentage of bone density was estimated as the proportion of bone tissue area relative to the total area of the interthread spaces, and the total number of Haversian canals was also counted.

ROI: region of interest.

Figure 5. Representative histologic findings in the (A) high-CS and (B) control groups. The regions surrounded by the red dotted square in each group are magnified. In the high-CS group, a greater amount of bone tissue in a more mature state, characterised by the presence of osteons, and a greater extent of bone-to-implant contact (indicated by white asterisks) were observed. In contrast, the control group exhibited a smaller amount of bone tissue in a less mature state around the implant fixtures.

Figure 6. Representative histologic images showing noteworthy findings in the control group. Severe resorption of the cortical plate was found, along with a periosteal-reaction-like appearance (red arrows) and a decrease in cancellous bone density.