Altundal H et al., 200438
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Alendronate significantly decreased the number of osteoclasts. An average of 2.6 ± 1.8 osteoclasts per measured area appeared in the alveolar crest region in the control group compared with an average of 1.3 ± 0.7 osteoclasts |
Day 14 and 28: Alendronate decreased the number of osteoblasts bordering alveolar bone and osteoblast activity. Osteoid formation both at days 14 and 28 was greater in the control group than in the alendronate group. |
Days 14 and 28: Alendronate decreased osteoid surface |
Days 14 and 28: Alendronate decreased bone fill and resulted in thicker alveolar bone in the buccal and lingual region of the extraction socket |
Days 14 and 28: Alendronate decreased interalveolar septum, number of osteoclasts, and resorptive lacunae, and increased alveolar bone thickness by preventing buccal and lingual bone loss by 95% and 98%, respectively |
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Hikita H et al., 200943
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Days 3 and 7: Alendronate decreased the number of osteoclasts per bone surface and tissue area; Day 14: Alendronate increased the number and enlarged; osteoclasts tended to be more deformed and larger, and their nuclei tended to be greater in number and aggregated to a greater extent in the alendronate group. |
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Alendronate decreased woven bone and increased granulation tissue. At 7 days, the extraction socket was completely filled with granulation tissue, and almost no new bone had formed in the extraction socket in the BP group. Ten and 14 days after tooth extraction the extraction socket was filled with newly formed bone. |
Day 7: Alendronate decreased bone fill at day 7 but at 14 days more prominent resorption was observed in the control group compared to the alendronate group with clearly higher new bone density in the alendronate group. |
Days 7,10, and 14: Alendronate decreased interalveolar septum resorption; Day 14: Alendronate decreased alveolar bone resorption. The proportion of newly formed bone increased in the alendronate group, ranging from 16.90 ± 8.66 at 3 days after extraction; 35.23 ± 9.62 (7 days); 64.76 ± 13.00 (10 days); and 74.99 ± 4.02 (14 days) |
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Aguirre JI et al., 201010
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Days 10 and 70: At 10 days, no differences were observed on eroded and osteoclast surfaces between the control group and the groups treated with either dose of alendronate. |
Day 10: Alendronate showed strong tendency to decrease osteoblast surface and number; |
Day 10: Moderate dosage of alendronate decreased 55% of woven bone volume compared to the control group and 75% at higher doses; Alendronate significantly decreased the osteoid surface, decreased mineralizing surface (45%), and bone formation rate (90%) |
Day 70: Both doses of alendronate increased cancellous and cortical bone mass (35.94 ± 10.71 and 36.01 ± 10.08) compared to the control group (19.61 ± 4.32) presumably due to their inhibitory effect on bone. |
Day 10: Alendronate decreased the eroded surface in the interalveolar septum (90%); Alendronate had higher interalveolar septum volume |
Day 10: ROI 2: Alendronate displayed a 2.5-fold increase in the percentage of empty osteocyte lacunae |
Day 10: Alendronate decreased blood vessel area (60%), number (45%) and perimeter (40%) The decline in these parameters was approximately 30% compared to vehicle-treated rats |
Day 10: In 3 out of 9 alendronate-treated rats the interdental alveolar bone exceeded the superficial surface of the socket, which was occupied by inflammatory tissue and not covered by oral epithelium. In these cases, the interdental bone appeared to be exteriorized in the oral cavity. |
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Alendronate decreases eroded surface |
ALN treatment induced a significant decrease in osteoblast surface (50%), mineralizing surface (45%), bone formation rate (90%) and eroded surface (90%) |
At day 70, the socket was almost completely filled with mature lamellar bone in alendronate group. |
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Maahs MP et al., 201147
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Day 105: Vascular endothelial growth factor (VEGF) was not statistically significant compared to the control group |
Day 105: Connective tissue (37.68 ± 9.36) was not statistically significant compared to the control group (36.70 ± 7.67) |
Day 105: Alendronate increased loss of mucosal integrity by 72.7% (7 rats out of 10) |
Day 105: Inflammatory infiltrate was present in 7 animals out of 11 (63.6%) without statistically significant differences. |
Day 105: Alendronate did not induce bone osteonecrosis in any of the animals. |
Kim JH et al., 201146
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Day 3,7,14 and 28: The number of osteoclasts did not differ from the control group, but there is reduction of osteoclast function in the alendronate group. |
Day 7: Osteoblast marker Collagen 1 was non-significant between alendronate and control groups. The function of osteoblast was not delayed |
Day 3,7 14 and 28: Woven bone is non-significant |
Day 3,7 14 and 28: There is no difference between Alendronate and control group in new bone formation in any of the periods evaluated. |
Day 7: Alendronate suppresses inter alveolar septum bone remodeling |
Day 7: Alendronate significantly increases empty osteocytic lacunae (74.33 ± 10.50) compared to control (41.67 ± 15.50) |
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Day 7: Connective tissue was not statistically significant |
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Abtahi J et al., 201237
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Day 14: Alendronate group showed small bone sequestra (3 out of 10 rats). |
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Day 14: The alendronate and control groups showed an intact overlying mucosa without differences between them. |
Day 14: Alendronate decreased inflammation |
Day 14: Alendronate did not induce osteonecrosis |
Berti–Couto SA et al., 201439
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Empty osteocytic lacunae were not statistically significant when comparing alendronate and control groups. |
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Connective tissue in the alendronate group (38.6%) was not statistically significant compared to the control group (29.36%) |
Total mucosal coverage was not significant between the alendronate (12.12%) and control groups (13.37%) |
Inflammatory infiltrate was non-significant when comparing the alendronate (2.53%) and control groups (0.95%) |
Alendronate did not induce osteonecrosis |
Conte Neto N et al., 201311
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Day 3 and 28: The amount of connective tissue was non-significant when comparing alendronate and control animals |
Day 28: Alendronate exhibited only slight bone formation, restricted to the apical socket area |
Day 3: New bone present in both groups. Day 28: Animals treated with alendronate demonstrated retention of the interadicular septum, which was associated with bone necrosis and infection. |
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Day 3: The number of blood vessels was not significant compared to the control group. Day 28:Alendronate decreased the number of blood vessels |
Day 28: Alendronate showed partial epithelial coverage exhibiting areas of bone exposure. Control animals showed total epithelial coverage without signs of inflammation. |
Day 28: Alendronate induced bone exposure; |
Day 28: Alendronate sustained a chronic inflammatory process |
Day 28: Alendronate group presented a significant increase in areas with necrotic bone in interalveolar septum and alveolar crest |
Khojasteh A et al., 201345
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Alendronate suppressed bone remodeling |
Day 60: Alendronate increased empty osteocytic lacunae and bone sequestra |
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Day 60: Alendronate impaired epithelial coverage. Wounds were not healed completely. |
Day 60: Alendronate induced mixed inflammation characterized by the combination of live and necrotic bone |
Day 60: Alendronate induced osteonecrosis |
Yamamoto-Silva FP et al., 201350
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Day 7: Alendronate induces atypical osteoclasts morphology; Day 21: Alendronate induced apoptosis in osteoclasts |
Day 7,14 and 21: Alendronate decreases the number of osteoblasts |
Day 7 and 21: Alendronate decreases woven bone (immature bone) while the formed immature bone filled less than 25% of their alveolar sockets. |
Day 7, 14 and 21: Alendronate decreases bone formation. At day 7 (0%), 14 (≈10%) and 21 (≈20%) small amount of new bone formation was observed compared to the control group at days 7 (≈40%), 14 (≈60%) and 21 (≈60%). |
Day 7,14 and 21: Alendronate inhibited crest resorption; Day 21: Alendronate suppressed alveolar bone remodeling |
Day 14 and 21: Alendronate increased empty osteocytic lacunae |
Day 7: Alendronate decreased new vessels formed in the apical region (endoglin, CD105) |
Day 7: Alendronate group presented significant inflammatory infiltrate; Day 14: The alendronate group presented with chronic inflammatory infiltrate in the connective tissue. |
Day 7: Alendronate induced no epithelial coverage. Day 14: Alendronate impaired epithelial coverage, which presented bacterial contamination. |
Days 7 and 14: Alendronate increased inflammatory infiltrate |
Day 14: Alendronate increased bacterial contamination and necrotic bone |
Yamazaki T et al., 201351
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Day 14: Alendronate increased the number of nonfunctional osteoclasts, exhibiting lack of ruffled border situated away from the bone surface |
Day 7: Alendronate decreased the number of osteoblasts |
Days 7, 14 and 28: Alendronate increased granulation tissue |
Day 7: The alendronate group showed small amount of new, immature bone of extraction. Day 14: newly formed bone in the socket has an irregular mesh and granulation tissue. The newly formed bone (≈60%) lacks the bone-like fiber bundle. Day 28: Alendronate decreased bone formation. |
Day 7: Resorption of the interalveolar septum was detected.Day 14: Alendronate inhibits crest resorption. Day 14 and 28: Alendronate suppressed bone remodeling, and thickening the cavity wall |
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Day 14; Alendronate group showed that the newly formed bone lacks the bonelike fiber bundle |
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Tanoue R et al., 201549
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Day 10: Alendronate decreased the number of osteoclasts |
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Days 3,5,7,10 and 21: Bone formation in the alendronate group was not different compared to the control group in any of the periods evaluated. |
Days 3,7 and 10: Alendronate increased the number of neutrophils and suppressed bone remodeling |
Days 3,7 and 10: Alendronate increased the average percentage of the empty osteocytic lacunae |
Days 3,5,7,10 and 21: blood vessel area was not significant compared to the control animals; Days 7 and 21: Alendronate decreased lymphatic vessel area |
Day 21: Alendronate decreased collagen apposition (≈65%) compared to the control group (≈80%) |
Day 10: epithelial coverage was not found in all the wounds in the alendronate and control groups; Day 21: Total epithelial coverage was observed in the alendronate and control groups (100%). |
Days 5,7,10 and 21: Alendronate increased the number of neutrophils and sustained inflammation |
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Conte Neto N et al., 201641
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Day 28: Alendronate decreased bone formation (≈40%) compared to the control group (≈80%). |
Day 28: Alendronate suppressed interalveolar septum bone remodeling, which was associated with bone necrosis and infection. |
Day 28: Alendronate increased empty osteocytic lacunae |
Day 28: Alendronate decreased vascularization |
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Day 28: Alendronate induced bone exposure with a marked impairment of alveolar socket re-epithelialization compared to the control group. |
Inflammation in the alendronate group was not significantly different compared to the control group. |
Day 28 Alendronate increased area of necrotic bone in the interadicular septum |
Saulacic N et al., 202048
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Week 8: Alendronate increased the number of non-attached osteoclasts in the bone surface. |
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Week 8: Formation of woven bone from the original bone at the apical and lateral portion of the extraction socket |
Week 8: Alendronate treatment increased vertical distance between the lingual and the buccal bone crest at root sites (1.48±1.37) compared to control group (1.28±0.28); and at extraction socket (2.16±0.74) and (0.76±0.05) in the alendronate and control group, respectively. |
Week 8: Alendronate suppressed bone remodeling and did not prevent resorption of the buccal bone of the extraction socket. Percentage of mineralized bone was non-significant between alendronate and control (24.9±22.63; 35.68±32.61) as well as the total bone (39.9±34.9; 30.42±28.32) for alendronate and control |
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Week 8: Connective tissue was not significant different between alendronate (39.9±34.99) compared to control (30.42±28.32) |
Alendronate did not impair epithelial coverage and the extraction socket was covered with oral mucosa lined with a keratinized epithelium. |
Modest signs of inflammation at one week; no inflammation after 2 and 8 weeks |
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Isaias PHC et al., et al52
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Some osteoclasts with signs of intracytoplasmic vacuolization and a few small bone sequestrations were observed in animals continuously treated with alendronate at doses of 5.0 and 7.5 mg/kg |
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The animals treated continuously with alendronate at the highest dose (7.5 mg/kg) showed significantly larger areas of fibrous tissue filling the alveoli of the left lower first molar |
Animals in the alendronate group had areas of their extraction sites partially filled with bone, fibrous connective tissue, and mononuclear inflammatory infiltrate |
Few small bone sequestrations were observed in animals continuously treated with alendronate at doses of 5.0 and 7.5 mg/kg |
The bone tissues exhibited empty osteocyte lacunae in alendronate-treated animals (Fig. 5f–h), but to a lesser extent when compared to ZA group |
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Animals in the alendronate group had areas of their extraction sites partially filled with fibrous connective tissue |
Alendronate increased mononuclear inflammatory infiltrate |
Alendronate did not induce osteonecrosis at doses of 2.5, 5.0 and 7.5 mg/kg |
Goncalves FC et al., 202242
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Day 30: Alendronate impaired socket healing with rats presenting extraoral fistulas, edema, and exposed bone |
Day 30: Alendronate maintained bone volume; however, the bone was necrotic |
Day 30: Alendronate increased the areas of empty osteocytic lacunae |
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Day 30: Alendronate did not impair fibroblast content |
Day 30: Alendronate group presented with extraoral fistulas and exposed bone. |
Day 30: Alendronate increased inflammatory infiltrate in the alveolar socket |
Day 30: Alendronate increased the amount of necrotic bone (28.2±24.9%) compared to the control group (17.3±13%) |
Goncalves FC et al., 202353
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Alendronate showed greater maintenance of mineralized tissues in the alveolar process after tooth extraction compared to the CTR. |
Alendronate suppressed alveolar bone remodeling with great amount of necrotic bone |
The interadicular and interdental septa of the extraction region were necrotic, characterized by the absence of osteocytes and empty gaps and a lack of bone resorption |
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In the alendronate group, the alveoli presented without epithelial tissue cover |
Alendronate did no increase inflammatory infiltrate in the alveolar socket |
The alendronate group presented more necrotic bone than the other groups (24.60% vs. 0.00% – CTR and ALN/IRL; 8.73% ALN/RL |