Effect of the cumulative dose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws

Günaldı, Meral; Afşar, Çiğdem Usul; Duman, Berna Bozkurt; Kara, İsmail Oğuz; Tatlı, Ufuk; Şahin, Berksoy

doi:10.3892/ol.2015.3156

Cited by 14 publications

(19 citation statements)

References 35 publications

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“…Bisphosphonates (BPs) are a class of drugs that are widely used for the treatment of various diseases related to bone loss such as osteoporosis, primary bone cancer or bone metastasis, and Paget disease (Günaldi et al 2010; Bauer et al 2012). Based on their high affinity for bone hydroxyapatite, BPs are incorporated in the bone matrix and enter osteoclasts during bone resorption.…”

Section: Introductionmentioning

confidence: 99%

Bisphosphonates as Supplement to Dental Treatment: A Network Meta-Analysis

et al. 2020

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The objective of this study was to assess clinical measurements related to the effectiveness of bisphosphonate (BP) administration as a supplement to conventional dental treatment in patients free of bone-related diseases using a network meta-analysis. Only randomized controlled trials (RCTs) were included that provided dental clinical measurements on human patients treated with BPs with or without similar untreated controls or treated with placebo. Information sources included a systematic search of 17 electronic databases up to August 2020, complemented by manual searches. Risk of bias assessment was performed with the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Extracted measurements were pooled according to time of evaluation. The random-effects model by DerSimonian and Laird was used to calculate mean differences (MDs) and the respective 95% confidence intervals (CIs). Seven RCTs were included in the network meta-analysis, assessing 391 subjects reporting on periodontal treatment effects after 2 to 12 mo of BP administration. BP treatment was associated with significant improvement of most clinical measurements, compared with BP-naive controls. According to the network ranking, alendronate was more efficient in improvement of probing depth and clinical attachment gain when compared to zoledronate or alendronate/risedronate. Similarly, the local application of alendronate as a gel was more effective than the oral administration. A long-term analysis of the pharmaceutical effects was not possible due to insufficient data. The current review, performed according to existing guidelines, included only RCTs and, through appropriate statistical analyses, provided precise estimates for most assessed outcomes. However, no adverse effects or long-term treatment results were analyzed due to inadequate pertinent data. BP administration seems to be beneficial in the short term for the treatment of periodontal diseases, mainly through controlling periodontal inflammation.

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Section: Introductionmentioning

confidence: 99%

Bisphosphonates as Supplement to Dental Treatment: A Network Meta-Analysis

et al. 2020

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“…Furthermore, the minor damage of aging bone tissues cannot be repaired, and the defense function against external trauma and infection invasion was reduced. This would induce the accumulation of inflammation damage, which is a vicious circle that leads to osteocyte necrosis, and the occurrence of jaw necrosis [ 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Determination of the molecular mechanism by which macrophages and γδ-T cells contribute to ZOL-induced ONJ

Qu¹,

Wang²,

Zhou³

et al. 2020

aging

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Objective: This study aims to explore the molecular mechanism of macrophages and γδ-T cells in the ZOL drug-induced osteonecrosis of jaws based on the IFN-γ involved osteoblast differentiation signaling pathway. Results: The number and apoptotic rate of CD11b+Gr1hi cells and γδ-T cells in the ONJ group were significantly higher. The TNF-α, IL-1β, IFN-γ, CCL3, CCL4, IL-12 and IL-13 levels were significantly higher in the ONJ group. The expression of CTSK and FGFR3 was lower in the ONJ group, but was higher in the NF-κB and ERBB2IP group. Conclusion: The proliferation of macrophages and γδ-T cells promote the inflammation in ZOL-induced jaw necrosis. Methods: A total of 20 patients with osteonecrosis of the jaw from January 2016 to March 2018 were collected and assigned into the observation group, while 20 healthy subjects were assigned into the control group. Furthermore, 40 SD rats were selected and assigned into observation group, while 10 non-treatment SD rats were selected and assigned as controls. The distribution and proportion of CD11b+Gr1hi cells and γδ-T cells in the necrotic tissues of the jaw were analyzed. Then, the TNF-α, IL-1β, IFN-γ, CCL3, CCL4, IL-12 and IL-13 levels were measured. Afterwards, the expression of CTSK, FGFR3, NF-κB and ERBB2IP in the necrotic tissues of the jaw in the animal models were analyzed.

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“…F I G U R E 1 Typical ONJ with exposed jaw bone Several reports emphasise not only on the type of administered antiresorptive agent but also in the cumulative dose (Gunaldi et al, 2015), number of infusions (Kajizono et al, 2015) and the duration bisphosphonate therapy (Bamias et al, 2005). Longer exposure seems to increase the incidence of ONJ.…”

Section: Systemic Risk Factorsmentioning

confidence: 99%

Antiresorptive treatment-associated ONJ

Eleutherakis‐Papaiakovou

Bamias

2017

Eur J Cancer Care

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Osteonecrosis of the jaw (ONJ) is a severe complication of therapy with antiresorptive agents (e.g. bisphosphonates and denosumab), which are used to manage bone metastases from cancer, to reduce the incidence of skeletal-related events. Available data indicate that 0-27, 5% of patients exposed to antiresorptive agents may develop ONJ, depending on the number of infusions and the duration of therapy. Besides antiresorptive therapy, a number of risk factors for osteonecrosis have been identified. Oral surgical procedures, tooth extractions and infection to the jawbones are considered the main risk factors for developing ONJ, when receiving antiresorptive therapy. However, a growing number of patients develop ONJ without apparent risk factors, raising concern for other predisposing factors. Jaw bone necrosis may be irreversible, resulting in a chronic disease with negative impact on the quality of patients' lives. The role of risk reduction strategies like meticulous dental screening and optimal oral hygiene is fundamental for preventing development of ONJ. ONJ is usually treated conservatively to relieve the symptoms and manage jaw bone necrosis. In certain cases, surgical intervention is required. Future research should emphasize individual predisposition to ONJ, more effective preventive measures and more efficient therapeutic procedures.

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Effect of the cumulative dose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws

Cited by 14 publications

References 35 publications

Bisphosphonates as Supplement to Dental Treatment: A Network Meta-Analysis

Bisphosphonates as Supplement to Dental Treatment: A Network Meta-Analysis

Determination of the molecular mechanism by which macrophages and γδ-T cells contribute to ZOL-induced ONJ

Antiresorptive treatment-associated ONJ

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Effect of the cumulative dose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws

Cited by 14 publications

References 35 publications

Bisphosphonates as Supplement to Dental Treatment: A Network Meta-Analysis

Bisphosphonates as Supplement to Dental Treatment: A Network Meta-Analysis

Determination of the molecular mechanism by which macrophages and &#x3B3;&#x3B4;-T cells contribute to ZOL-induced ONJ

Antiresorptive treatment-associated ONJ

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Determination of the molecular mechanism by which macrophages and γδ-T cells contribute to ZOL-induced ONJ