Diminished Progression of Periapical Lesions with Zoledronic Acid in Ovariectomized Rats

Wayama, Marcelo Tadahiro; Yoshimura, Hitoshi; Ohba, Seigo; Yoshida, Hisato; Matsuda, Shinpei; Kobayashi, Jun’ichi; Kobayashi, Motohiro; Gomes‐Filho, João Eduardo; Sano, Kazuo

doi:10.1016/j.joen.2015.08.029

Cited by 25 publications

(25 citation statements)

References 32 publications

(23 reference statements)

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“…However, our study showed that PARL may not always be a good indicator for RCT in BP-users; in the presence of BPs, no PARL was detected despite prominent pulp exposure and the histological presence of inflammatory cells and osteoclasts (Fig.2 A ). Indeed, such reports were previously documented in other clinical and preclinical observations (23, 24). These findings imply that pulpal infection may be gone unnoticed during routine dental examination due to no radiographic lesions and that such conditions may be falsely classified as “spontaneous ONJ” or the “staging 0 ONJ.”…”

Section: Discussionsupporting

confidence: 63%

Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice

Song

Alshaikh

Kim

et al. 2016

Journal of Endodontics

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Introduction Surgical interventions such as tooth extraction increase a chance of developing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for treatment of bone-related diseases. Tooth extraction is often performed to eliminate pre-existing pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related ONJ (BRONJ) development following tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice. Methods Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BP. The same tooth was extracted, and after 3 additional weeks, the mice were harvested for histological, histomorphometric, and histochemical staining analyses. Results Pulp exposure induced periapical radiolucency as demonstrated by increased inflammatory cells, TRAP+ osteoclasts, and bone resorption. When BP was administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and TRAP+ osteoclasts. While tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as demonstrated by the presence of more bone necrosis. Conclusion Our study demonstrates that pre-existing pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development following tooth extraction. Our study further provides a clinical implication whereby periapical periodontitis should be controlled before performing tooth extraction in BP-users in order to reduce the risk of developing BRONJ.

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Section: Discussionsupporting

confidence: 63%

Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice

Song

Alshaikh

Kim

et al. 2016

Journal of Endodontics

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“…), bisphosphonates (Wayama et al . ), selective oestrogen receptor modulators (Gomes‐Filho et al . ) and cathepsin K inhibitors (Suzuki et al .…”

Section: Discussionmentioning

confidence: 99%

Anti‐inflammatory and antiresorptive functions of melatonin on experimentally induced periapical lesions

Sarıtekin¹,

Kaya²,

Aşçı³

et al. 2019

Int Endodontic J

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Aim To investigate the effects of systemically administered melatonin on inflammation and alveolar bone resorption in rats with experimentally induced periapical lesions. Methodology Thirty adult Sprague Dawley rats were divided equally into negative, positive control and melatonin groups. The pulp chambers of their mandibular first molars were exposed to the oral environment to induce experimental periapical lesions in the positive control and melatonin groups. The melatonin group received daily intraperitoneal injections of melatonin at a dose of 10 mg kg−1. After 21 days, the animals were euthanized; the hemi‐mandible parts were prepared for radiological, histopathological, immunohistochemical (IL‐1β, RANK, RANKL, OPG and tartrate‐resistant acid phosphatase (TRAP) and Brown–Brenn (bacteria) evaluations. Data were analysed by Kruskal–Wallis (for non‐parametric data) and one‐way anova tests (for parametric data) (P < 0.05). Results The area of radiographic periapical bone loss was significantly smaller in rats that were given daily intraperitoneal injections of melatonin (P < 0.01). The histopathological scores of the melatonin group were significantly lower than those of positive control group (P < 0.01). Histomorphometrically, the area of periapical bone loss in the melatonin group was significantly smaller than the positive control group (P < 0.01). The expression of IL1‐β, RANK and RANKL was significantly higher in the positive control group, whereas OPG was significantly higher in the melatonin group (P < 0.01). The number of osteoclasts was significantly greater in the positive control group by TRAP staining analyses (P < 0.01). The scores for bacteria localization using Brown–Brenn staining in the melatonin group was significantly lower than that of the positive control group (P < 0.01). Conclusions Melatonin demonstrated antiresorptive effects on bone associated with experimentally induced periapical lesions in rats via its anti‐inflammatory activity. Further studies are necessary to evaluate its possible effects on the healing of periapical lesions.

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“…() and Wayama et al . () reported that the periapical region in OVX animals had a higher amount of TRAP‐positive cells compared to sham animals. Also, Xiong et al .…”

Section: Discussionmentioning

confidence: 97%

“…, Wayama et al . , Romualdo et al . ), leading to an increase in the expression of proinflammatory cytokines and matrix metalloproteinases (Romualdo et al .…”

Section: Introductionmentioning

confidence: 99%

Alendronate inhibits osteocyte apoptosis and inflammation via IL‐6, inhibiting bone resorption in periapical lesions of ovariectomized rats

et al. 2019

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Aim To evaluate the effect of alendronate (ALN) on the development of periapical lesions induced in ovariectomized rats. Methodology Twenty‐five rats were divided into three groups: sham (control), ovariectomy (OVX) and OVX + ALN. One day after OVX, animals from the OVX + ALN group received the medication via gavage. After 9 weeks, the first molars of all animals were submitted to periapical lesion induction. After 21 days, the animals were euthanized. Femurs were analysed for bone mineral density. The blocks of bone tissue containing the mandibular first molars were submitted to histotechnical processing and staining with haematoxylin and eosin (HE) for periapical lesion analysis under conventional microscopy. At the same time, the morphometric analysis of the periapical lesion area was performed in the fluorescence mode, as well as the histoenzimology for the quantification of osteoclasts and 4′‐6‐diamidino‐2‐phenylindole staining for the quantification of apoptotic osteocytes. In addition, the first maxillary molars were used for analysis of the gene expression of proinflammatory cytokines (IL‐1β, IL‐6 and TNF‐α) and osteoclastogenesis markers (RANKL/OPG). The results were submitted to ANOVA and Kruskal–Wallis tests and Tukey and Dunn post‐tests (significance level of 5%). Results Ovariectomy reduced bone mineral density of the femur, and treatment with ALN was able to prevent bone loss (P < 0.001). Regarding the microscopic analysis of the periapical region, the sham and OVX + ALN groups had moderately increased periodontal ligament and inflammatory infiltrate, while the OVX group had these parameters increased intensely. The periapical lesions of the OVX group were significantly larger in area in comparison to the other groups (P < 0.001). The OVX group had the largest amount of apoptotic osteocytes, and ALN was able to prevent the apoptosis of these cells, in addition to significantly reducing IL‐6 expression (P < 0.05). OVX and ALN had no effect on RANKL/OPG expression and did not influence the number of osteoclasts around the periapical lesion (P > 0.05). Conclusion The hypoestrogenic condition induced by OVX aggravated bone resorption, inducing the death of osteocytes and provoking larger periapical lesions. ALN treatment inhibited osteocyte apoptosis and inflammation via IL‐6, inhibiting bone resorption in periapical lesions of ovariectomized rats.

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Diminished Progression of Periapical Lesions with Zoledronic Acid in Ovariectomized Rats

Abstract: The hypoestrogenic condition aggravates the progression of periapical lesions. ZOL therapy may help contain bone destruction of periapical lesions.

Cited by 25 publications

References 32 publications

Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice

Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice

Anti‐inflammatory and antiresorptive functions of melatonin on experimentally induced periapical lesions

Alendronate inhibits osteocyte apoptosis and inflammation via IL‐6, inhibiting bone resorption in periapical lesions of ovariectomized rats

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