Effect of zoledronic acid on bone healing subsequent to mini-implant insertion

Abstract

Objective: To examine remodeling in bone supporting mini-implants by comparing a no drug (ND) group with a group that received a potent intravenous bisphosphonate in a canine model.

Materials and methods: Twelve skeletally mature (2- to 3-year-old) male dogs were divided into two groups. Seven dogs were administered 0.1 mg/kg/mo of zoledronic acid (ZA) for 16 weeks, while five age-matched dogs received no drug. Two mini-implants (Tomas, Dentaurum, Newton, Pa) were placed unilaterally in the maxilla and mandible (4 mini-implants per animal × 12 = 48). Serial fluorescent bone labels were administered in vivo. Postmortem, the bone blocks containing the mini-implants were harvested and used for histomorphometric analyses at two regions of interest (adjacent: within 1 mm of interface; distant: 1-4 mm from the interface) supporting the mini-implant. Data were analyzed using mixed models.

Results: In general, the ZA group had a significantly lower bone formation rate than the ND group (P < .05) for all jaws/regions except for the adjacent region in the maxilla, P = .12. Despite the reduction, mean intracortical remodeling in the ZA group ranged from 35%-42% per year in the implant adjacent bone. This rate is substantially higher than that reported for noninjured sites in the jaw.

Conclusions: Bone remodeling is typically elevated in implant supporting bone. After ZA administration, the healing response represented by elevated turnover in implant supporting bone was diminished but was not abolished.

Figure 1

Schematic of timeline. T₀–T₁₀ indicate events on the timeline. T₀ is arrival and 1 week is given for acclimatization, prior to first bone label, T₁–T₇ is surgical (S) mini-implant placement. T₁₀ is time at harvest of tissue. The 1w, 2w, 4w, and 6w indicate the time in weeks between the time points. A₁ and A₂ indicate alizarin label, D₁ through D₄ is the drug administration (zoledronic acid). C₁ and C₂ represent the calcein labels. The only treatment difference between the two groups was the lack of any drug treatments in the ND group.

Figure 2

Faxitron images of the maxilla (a,c) and the mandible (b,d) at harvest. In this animal, mini-implants were placed on the right side (a,b) while no implants were placed on the left side (c,d). The mini-implants were placed in the interradicular regions of the second and fourth premolar in the maxilla. In the mandible, the mini-implants were placed in the interradicular region of the second premolar (note implant lost) and first molar.

Figure 3

Schematic of histomorphometric quantification. The schema represents the mini-implant in the mandible. The implant supporting bone is divided into adjacent and distant regions. Adjacent bone boundary is defined as bone from the interface to the dotted line, which is approximately 1 mm from the interface. The distant bone extends from 1 mm from the interface to 4 mm from the interface. There are two sides to the implant, the coronal being towards the tooth and the apical towards the basal bone. The adjacent and distant bone on both sides of the implant was quantified with aid of the Merz grid which is represented by the square. Essentially all the bone in the coronal and the apical sides of the implant in both the adjacent and distant regions was analyzed by standard dynamic histomorphometric methods.

Figure 4

Comparison of alizarin and calcein labeled bone formation rate (BFR, % per year, mean, SD) in the (A) ZA and (B) ND groups for mini-implant adjacent (near) and distant bone. There is a significant (P < .01) increase in BFR in both groups except for the distant bone in the ZA group (P > .05). The healing response results in increase in calcein label in the ZA group distant bone but not to the extent in the ND group. Note that scales of the bar graphs in A and B are different.