Table 1.
Staging and treatment strategies for BRONJ.
Fig 1.
Application of a gelatin hydrogel sheet incorporating bFGF.
(a) The lower first molar before extraction. (b) After tooth extraction, the extraction socket was expanded with a twist drill to create a bone defect (open arrow). (c) The alveolar defect after applying a gelatin hydrogel sheet (open arrowhead). (d) The bone defect was sutured primarily (filled arrow).
Fig 2.
Setting of the region of interest (ROI) and the volume of interest (VOI) in the alveolar defect.
(a) The ROI was set at 1.0-mm mesial from the mesial surface of the lower second molar on the CT coronal section. The tangent line passing through the highest point of the incisor, parallel to the occlusal plane, was set as the x-axis, and the perpendicular line passing through that point was set as the y-axis. The highest point of the incisor was set as the origin, and a square region of 0.5 mm × 0.5 mm with vertices at (x, y) = (1 mm, 1 mm), (1 mm, 1.5 mm), (1.5 mm, 1 mm), (1.5 mm, 1 mm), and (1.5 mm, 1.5 mm) was defined as the ROI. (b) By auto-interpolation between layers, ROI became the volume of interest (VOI) in the area between the coronal sections 1.0- and 1.5-mm mesial from the mesial surface of the lower second molar. The volumes of the newly formed bone in this VOI were determined 3 and 8 weeks after tooth extraction, and compared among the study groups. (2D, two-dimensional view; 3D, three-dimensional view; 2 M, lower second molar; 3 M, lower third molar).
Fig 3.
(a) Extraction socket in the bFGF group at 3 weeks after tooth extraction. (b) Extraction socket in the PBS group at 3 weeks after tooth extraction. (c) Extraction socket in the control group at 3 weeks after tooth extraction. (d) Extraction socket in the bFGF group at 8 weeks after tooth extraction. (e) Extraction socket in the PBS group at 8 weeks after tooth extraction. (f) Extraction socket in the control group at 8 weeks after tooth extraction. The extraction sockets in the bFGF group at 3 and 8 weeks (a, d) after the tooth extraction socket was covered with normal mucosa, similar to the surrounding areas, and demonstrating no signs of inflammation. The concavities of the sockets were still present at 3 weeks after tooth extraction (a), but there was no residual socket concavity at 8 weeks after tooth extraction (d). The extraction sockets in the PBS group (b) and the control group (c) at 3 weeks after tooth extraction showed exposed bone of normal color. The extraction sockets in the PBS group (e) and the control group (f) at 8 weeks after tooth extraction showed discolored, brownish exposed bone.
Table 2.
The incidence of extraction sockets with exposed bone based on macroscopic findings.
Fig 4.
(a) Alveolar defect in the bFGF group immediately after tooth extraction. (b) Alveolar defect in the bFGF group at 3 weeks after tooth extraction. (c) Alveolar defect in the PBS group at 3 weeks after tooth extraction. (d) Alveolar defect in the control group at 3 weeks after tooth extraction. (e) Alveolar defect in the bFGF group at 8 weeks after tooth extraction. (f) Alveolar defect in the PBS group at 8 weeks after tooth extraction. (g) Alveolar defect in the control group at 8 weeks after tooth extraction. There was no bone formation in the alveolar defects in any group at 3 weeks after tooth extraction (b–d). Whereas bone formation was found in the bFGF group (e) at 8 weeks after tooth extraction, no such bone formation was found in the PBS group (f) and the control group (g), but small bone fragments suggestive of bone sequestra were present at this time point.
Fig 5.
The volume of newly formed bone in the extraction socket.
The volume of newly formed bone in the bFGF group at 8 weeks after tooth extraction was significantly greater than the corresponding volumes in the PBS group and the control group at 8 weeks after tooth extraction, as well as in the bFGF group at 3 weeks after tooth extraction. Each error bar denotes 1 standard error.
Fig 6.
Typical histological findings.
(a) Alveolar defect in the bFGF group immediately after tooth extraction. The gelatin hydrogel applied in the defect is indicated as a dotted line. (b) Alveolar defect in the bFGF group at 3 weeks after tooth extraction. (c) Alveolar defect in the PBS group at 3 weeks after tooth extraction. (d) Alveolar defect in the control group at 3 weeks after tooth extraction. (e) Alveolar defect in the bFGF group at 8 weeks after tooth extraction. (f) Alveolar defect in the PBS group at 8 weeks after tooth extraction. (g) Alveolar defect in the control group at 8 weeks after tooth extraction. There was no mucosal disruption in the bFGF group at 3 and 8 weeks after tooth extraction (b, e). The defect was filled with granulation tissue (*) and new bone (NB) at 3 and 8 weeks after tooth extraction, respectively. Numerous osteocytes were presented in their lacunae in the bFGF group at 3 and 8 weeks after tooth extraction (inset b, e). In the group, mild infiltration of inflammatory cells, consisting mainly of neutrophils, was observed with multinucleated giant cells at 3 weeks after tooth extraction, but the infiltration was scarce at 8 weeks after tooth extraction. Mucosal disruption (black line) was present in the PBS group (c, f) and in the control group (d, g) at 3 and 8 weeks after tooth extraction, and there was no bone formation. Numerous empty osteocyte lacunae were observed in the PBS group and in the control group at 3 and 8 weeks after tooth extraction (inset c, d, f, g). Additionally, severe inflammatory cell infiltration, mainly comprising neutrophils, was observed in the PBS group and the control group at 3 and 8 weeks after tooth extraction (hematoxylin and eosin stain; original magnification ×4, inset magnification ×40).
Table 3.
Histologic findings of each group.
Fig 7.
The total number of empty osteocyte lacunae per extraction socket.
The total number of empty osteocyte lacunae per extraction socket in the bFGF group at 3 and 8 weeks after tooth extraction was significantly lower than the total empty osteocyte lacunae in the PBS group and the control group at 3 and 8 weeks after tooth extraction. Each error bar denotes 1 standard error.