Atorvastatin reduces zoledronic acid-induced osteonecrosis of the jaws of rats

Sousa, Vanessa Costa de; Sousa, Fátima Regina Nunes de; Vasconcelos, Raquel Felipe de; Martins, Carla Adriano; Lopes, Amanda P.; Alves, Nicholas Militão; Viana, Delane; Alves, Karuza; Leitão, Renata F. C.; Brito, Gerly Anne Castro; Girão-Carmona, Virgínia Cláudia Carneiro; Góes, Paula

doi:10.1016/j.bone.2022.116523

Cited by 8 publications

(5 citation statements)

References 55 publications

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“…Wnt signaling was found to be suppressed in the DRONJ model, and this was ameliorated by administering DPSC-CM. Although Wnt signaling is reported to be suppressed in the rat BRONJ model [ 32 , 33 ], some reports have shown that Dkk-1 was not suppressed, unlike in the present findings. Dkk-1 is an inhibitor of Wnt signaling and binds to the co-receptor low-density lipoprotein receptor-related protein, which activates intracellular disheveled and degrades the signaling molecule β-catenin [ 34 ].…”

Section: Discussioncontrasting

confidence: 96%

Preventive Effects of Dental Pulp Stem Cell-conditioned Media on Anti-RANKL Antibody-Related Osteonecrosis of the Jaw

Kaminogo,

Yamaguchi,

Chen

et al. 2024

Calcif Tissue Int

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Medication-related osteonecrosis of the jaw is a serious disease occurring in patients with cancer and osteoporosis, who are undergoing treatment with antiresorptive agents (ARAs) such as bisphosphonate (BP) or denosumab, an antibody targeting receptor activator of NF-κB ligand. Recently, stem cell-based therapy has been shown to be effective in preventing the development of bisphosphonate-related osteonecrosis of the jaw. However, studies on denosumab-related osteonecrosis of the jaw (DRONJ) remain limited. Here, the efficacy of treatment with dental pulp stem cell conditioned media (DPSC-CM) in preventing DRONJ in a murine model was evaluated. Local administration of DPSC-CM into the extraction socket of a mouse with DRONJ decreased the number of empty osteocyte lacunae and the prevalence of ONJ. In tissues surrounding the extraction sockets in the DPSC-CM-treated group, the expression of inflammatory cytokines was attenuated and that of osteogenesis-related molecules was enhanced compared to that in the control group. Further, the expression of Wnt signaling molecules, which had been suppressed, was improved. These findings collectively suggest that DPSC-CM prevents ONJ development in a murine DRONJ model.

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Section: Discussioncontrasting

confidence: 96%

Preventive Effects of Dental Pulp Stem Cell-conditioned Media on Anti-RANKL Antibody-Related Osteonecrosis of the Jaw

Kaminogo,

Yamaguchi,

Chen

et al. 2024

Calcif Tissue Int

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“…On the other hand, short-term use of statins was shown to have many bene cial effects on oral health [44], including aiding the healing of the extraction socket [45]. In fact, uvastatin and atorvastatin have therapeutic effects on MRONJ and/or can act protectively [46,47,48,49]. This is in line with the decreased risk of osteonecrosis of the femoral head when glucocorticoids are combined with statins [50].…”

Section: Discussionmentioning

confidence: 99%

Single low-dose of denosumab as a triggering agent for MRONJ development in a patient with osteoporosis Case report and mini-review

Szaraz

Peřina

Treglerová

et al. 2023

Preprint

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Both denosumab (DNO) and bisphosphonates (BP), antiresorptive drugs (ARDs) used for the treatment of osteoporosis and oncological disorders, are known for their potential to cause medication-related osteonecrosis of the jaws (MRONJ). Besides ARDs, statins were recently associated with MRONJ development, especially in patients taking higher doses of statins for a longer period of time. Here, we report a case of a woman with osteoporosis who rapidly developed MRONJ stage III after only a single low dose of DNO. The patient was taking statins (rosuvastatin) for 7 years and had also been on BP (alendronate) for 4 years previously but this treatment was discontinued for approximately 1.5 years before MRONJ development. We performed a literature review of cases with MRONJ triggered by a single low dose of DNO and of cases with statin-induced MRONJ in patients not using ARD. Because the MRONJ development after a single low dose of DNO is rare, only eleven cases were previously described. We suggest that (i) in some patients, long-term use of statins and BP may lead to a higher susceptibility of MRONJ development after DNO exposure and (ii) that all predisposing factors to MRONJ development including the necessity of any dental procedures should be considered before DNO therapy is initiated.

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“…For this study, 54 female Wistar rats (12 weeks old, ± 200 g) ( Rattus novergicus) were used. The sample size of 6 animals per group was determined in order to provide a power calculation of 80%, and significant level of p < 0.05, considering bone necrosis, defined by the percentage of empty lacunae of osteocytes (> 50% in 05 fields/slide) and presence of bone sequestration as the primary outcome variable 6 , 14 .…”

Section: Methodsmentioning

confidence: 99%

“…Three spectra of each sample were collected. For the standardization acquisitions were carried out in two distinct points, inside and outside the dental alveolus 6 , 14 . The data were obtained by a LabSpec 6 software data acquisition command system (Horiba, JobinYvon, Paris, France) and analyzed by the Origin 9 program (Originlab© Corporation, One Roundhouse Plaza, Northampton, MA 01060, USA).…”

Section: Methodsmentioning

confidence: 99%

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Polysacharide of Agaricus blazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling

Costa de Sousa,

Nunes Sousa,

Felipe Vasconcelos

et al. 2024

Sci Rep

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To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

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Atorvastatin reduces zoledronic acid-induced osteonecrosis of the jaws of rats

Cited by 8 publications

References 55 publications

Preventive Effects of Dental Pulp Stem Cell-conditioned Media on Anti-RANKL Antibody-Related Osteonecrosis of the Jaw

Preventive Effects of Dental Pulp Stem Cell-conditioned Media on Anti-RANKL Antibody-Related Osteonecrosis of the Jaw

Single low-dose of denosumab as a triggering agent for MRONJ development in a patient with osteoporosis Case report and mini-review

Polysacharide of Agaricus blazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling

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