Sclerostin-Neutralizing Antibody Enhances Bone Regeneration Around Oral Implants

Abstract

Background: Dental implants are an important option for replacement of missing teeth. A major clinical challenge is how best to accelerate bone regeneration and reduce the healing time for functional restoration after implant placement. A sclerostin-neutralizing antibody (Scl-Ab) has been shown to enhance alveolar bone formation and fracture repair. The aim of this study was to investigate the effects of systemic administration of Scl-Ab on dental implant osseointegration and bone regeneration in an experimental alveolar ridge tooth extraction model.

Materials and methods: To investigate the effects of Scl-Ab on bone regeneration and dental implant osseointegration, an experimental alveolar bone osteotomy rat model was adopted. One month after extraction of maxillary right first molars, osteotomy defects were created at the coronal aspect of each of the extraction sites, and 1 × 2-mm custom titanium implants were installed into the osteotomies. Coincident with implant placement, Scl-Ab was administered subcutaneously at a dose of 25 mg/kg twice weekly for 10-28 days and compared with a vehicle control. Animals were sacrificed 10, 14, and 28 days after surgery, and maxillae were harvested and analyzed by microcomputed tomography (microCT), histology, and histomorphometry.

Results: microCT analysis demonstrated that the maxillary bone volume fraction was approximately 2- to 2.5-fold greater in Scl-Ab-treated animals compared with vehicle alone at days 14 and 28. Consistent with those findings, two-dimensional bone fill percentages within the coronal osteotomy sites were highest in Scl-Ab treatment groups at 28 days. In addition, bone-implant contact at 28 days was approximately twofold greater in the Scl-Ab group compared with the vehicle control.

Conclusions: These results indicate that systemic Scl-Ab administration enhances osseointegration and bone regeneration around dental implants. This approach offers potential as a treatment modality for patients with low bone mass or bone defects to achieve more predictable bone regeneration at alveolar bone defects and to enhance dental implant osseointegration.

Keywords: bone anabolics; bone repair; dental implants; osseointegration; osseous healing; sclerostin.

FIG. 1.

Study design and time line. Implant surgery was performed 30 days after right maxillary first molar extraction. Following wound healing, osteotomies were created and titanium implants were placed concurrent with the initiation of twice-weekly systemic Scl-Ab administration. 3D evaluations (microCT imaging), histology, and histomorphometric measurements were performed at days 10, 14, and 28 after implant installation. 3D, three-dimensional; microCT, microcomputed tomography; Scl-Ab, sclerostin-neutralizing antibody.

FIG. 2.

Surgical procedures of maxillary molar extraction and implant placement. (A) Occlusal (top) view of maxillary right molars. (B) Socket after first molar extraction. (C) Socket wound healing 1 month after extraction. (D) Gingival flap design. (E) Flap reflection and alveolar ridge exposure. (F) Osteotomy created by a customized step drill. (G) Placement of the titanium implant into the osteotomy defect. (H) Application of collagen gel around the titanium implant. (I) Closure of the wound with tissue glue.

FIG. 3.

microCT images. Representative microCT images of maxillary alveolar bone surrounding the titanium implants at days 10, 14, and 28 after placement of dental implants. The yellow dotted line marks the approximate dimensions of the defect. Two-dimensional sagittal images and 3D images of maxillae show visual differences in bone formation around the dental implants between the Scl-Ab-treated group and the vehicle group.

FIG. 4.

Histology of resin-embedded sections of specimens with methylene blue and basic fuchsin staining. New bone formation was found in all the defects. Over time, osseointegration was also observed. Greater bone formation was seen in the Scl-Ab group compared with the phosphate-buffered saline vehicle group at days 14 and 28.

FIG. 5.

microCT assessments of BVF and TMD and histomorphometry measurements of BVF and BIC. (A) At day 14, the Scl-Ab group had more BVF than the vehicle group by t-test analysis (p < 0.05). Furthermore, the Scl-Ab group at day 28 presented the largest BVF through one-way ANOVA. (B) Assessment of TMD indicated no difference between Scl-Ab and vehicle groups. (C, D) The Scl-Ab group had the statistically greatest BIC and bone fill percentage at day 28 compared with the vehicle group, as analyzed by one-way ANOVA. ANOVA, analysis of variance; BVF, bone volume fraction; BIC, bone-implant contact; TMD, tissue mineral density.