Ultrastructural and immunohistochemical study of early repair of alveolar sockets after the extraction of molars from alendronate‐treated rats

Abstract

The aim of the present research was to analyze ultrastructural and immunohistochemical aspects of the alveolar repair after the extraction of molars of alendronate (ALN)-treated rats. Wistar rats received 2.5mg/kg body wt/day of ALN during 14 days previously and 7, 14 and 21 days after the extraction of the second mandibular molar. Specimens were fixed in 2% glutaraldehyde + 2.5% formaldehyde under microwave irradiation, decalcified in 4.13% EDTA and paraffin embedded for TRAP histochemistry and immunohistochemistry for OPN, BSP and endoglin, or embedded in Spurr epoxy resin for TEM analysis. Additional specimens had their soft tissues removed and were processed for scanning electron microscopy. The ALN group presented latent TRAP-positive osteoclasts and nonresorbed alveolar crests with bacterial infection. Mild bone necrosis signs were observed at all time points studied. Ultrastructurally, empty osteocyte lacunae were observed and bone trabeculae surface presented hyalinized aspect. A significant delay in alveolar repair occurred, as well as decreased angiogenesis. ALN treatment provoked mild signs of bone necrosis, despite the high dose employed. The present findings add new information about the ultrastructural aspect of the early repair of rats under ALN treatment and highlight for giving attention when oral surgeries are performed in patients using this drug.

Ultrastructural and immunohistochemical study of the effect of sodium alendronate in the progression of experimental periodontitis in rats

“…Most studies that aimed to interfere in alveolar bone resorption by osteoclasts employ bisphosphonates with higher anti‐resorptive potency like zoledronic acid (Aguirre et al, ). However, in the present study the ALN was employed because it is the most prescribed antiresorptive drug for the prevention and treatment of bone diseases (Russell, ) and usually comprises long‐term administration regimens, which represents a risk of developing osteonecrosis when associated to oral surgeries or pathologies like periodontal disease (Aghaloo et al, ; Yamamoto‐Silva et al, ). In the present study, a high dose of ALN proven to impair the bone resorption by osteoclasts (Bradaschia‐Correa et al, ) was daily administered to rats, starting seven days before the induction of the disease.…”

Medication‐related osteonecrosis of the jaw‐like lesions in rodents: A comprehensive systematic review and meta‐analysis

“…Moreover, Soundia et al reported that ZA and OPG‐Fc monotherapy significantly compromised bone healing of extracted healthy teeth with periradicular disease, whereas osseous healing of tooth extraction sockets was almost normal . On the other hand, Kim et al reported that ZA/Dex combination therapy and ZA monotherapy significantly increased glucose metabolism at the extraction site at 4 weeks after tooth extractionusing F‐fluorodeoxy glucose PET/CT, in accordance with the significant prevalence of BRONJ‐like lesions (Table ) …”

“…Zoledronic acid (ZA) and osteoprotegerin (OPG)‐Fc monotherapy were used to create BRONJ‐ and DRONJ‐like lesions in five studies, respectively, whereas ZA was administered in combination with chemotherapeutic agents and/or dexamethasone (DEX) to develop BRONJ‐like lesions in four studies . Alendronate monotherapy was also used to create BRONJ‐like lesions in one study . On the other hand, an anti‐angiogenesis agent‐related ONJ model has not been developed.…”

“…Maxillary and mandibular first molars were extracted in eight and two studies, respectively. Mandibular second molars were extracted in one study . All articles investigated the pathology and/or immunopathology and/or pathogenesis of BRONJ‐ and/or DRONJ‐like lesions.…”

“…Therefore, 32 studies were used for full-text evaluation. Finally, 10 articles met the inclusion criteria and were used in this study, [11][12][13][14][15][16][17][18][19][20] since the remaining 22 articles were excluded based on the inclusion and exclusion criteria ( Figure 1).…”