Does dental and oral health influence the development and course of bisphosphonate-related osteonecrosis of the jaws (BRONJ)?

Purpose

The main causes for the occurrence of bisphosphonate-related osteonecrosis of the jaws (BRONJ) are the application of aminobisphosphonates and the extraction of teeth. However, the question which factors in dental and oral health are relevant has not been answered completely.

Materials and methods

In a retrospective study, 50 patients who were treated with BRONJ between 2000 and 2009 were analyzed. As underlying diseases, they suffered from breast cancer (n?=?24), multiple myeloma (n?=?16), prostate cancer (n?=?5), osteoporosis (n?=?4), and kidney cancer (n?=?1). The data were collected from the patient charts of the treating dentists, oral and maxillofacial surgeons, general practitioners, and oncologists. The time of occurrence of BRONJ after treatment onset with bisphosphonates (BP) was examined with Kaplan–Meier estimator and logrank test (level of significance 0.05).

Results

At the time of BP treatment, onset the decayed, missing, and filled teeth (DMFT) index was 20.5?±?4.2. Patients with a DMFT value less than 20 showed a significantly longer BRONJ-free time interval after BP treatment onset with 39.7?±?1.1 months compared to patients with a DMFT value higher than 20, in whom BRONJ appeared after 14.4?±?2.8 months (p?<?0.001). However, the DMFT value had no influence on the success rate of BRONJ treatment. As a pre-existing oral disease, 60 % of the patients (n?=?30) had marginal periodontitis; 38 % (n?=?19), apical periodontitis; and 22 % (n?=?11), a pressure lesion from their dentures. In patients with marginal periodontitis, BRONJ occurred after 26.3 months (range 20.9–31.3) and in patients without marginal periodontitis, after 27.4 months (range 14.6–40.1) (p?=?0.58). Only 20 % of the patients with marginal periodontitis received adequate treatment. Without parodontal treatment, BRONJ occurred 15 months earlier compared to patients with parodontal treatment (p?=?0.12). The state of the periodontium did not influence the healing rate of BRONJ (p?>?0.999).

Conclusion

The present study highlights the great benefit of good dental and oral health in the prevention of BRONJ; but it also shows that after the appearance of BRONJ, these factors do no longer seem to play a relevant role in the disease course.     

Bisphosphonates’ antiangiogenic potency in the development of bisphosphonate-associated osteonecrosis of the jaws: influence on microvessel sprouting in an in vivo 3D Matrigel assay

Objectives

Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is an adverse side effect of long-term bisphosphonate treatment. One theory of BP-ONJ etiology suggests a negative influence of these agents on angiogenesis and vascularization. This in vivo study analyzed the effects of bisphosphonates on angiogenesis in a 3D Matrigel assay.

Materials and methods

Matrigel plugs were implanted into fifty 6–8-week-old female nude mice. Ten animals each were treated either with clodronate, ibandronate, pamidronate, zoledronate, or carrier solution as controls. The microvessel density (MVD), microvessel area (MVA), and microvessel size (MVS) in Matrigel plugs were analyzed after 21 days of treatment by immunohistochemistry and exemplary 3D microvascular corrosion castings.

Results

All bisphosphonates induced a statistically significant decrease of MVD (p each <0.001), whereby the nitrogen-containing bisphosphonates (N-BPs) demonstrated a clearly stronger effect than non-nitrogen-containing bisphosphonates (NN-BP) clodronate (control 166, clodronate 99, ibandronate 48, pamidronate 47, zoledronate 35 microvessels/mm²). Referring to MVA, similar results could be detected. MVS was significantly increased especially by ibandronate (103 %) compared to control group (p?<?0.001). Scanning electron microscope scans of the corrosion castings confirmed these results.

Conclusions

The stronger influence on MVD by N-BPs compared to the NN-BP clodronate may explain for the lack of BP-ONJ after treatment with NN-BPs.

Clinical relevance

Ibandronate induced a strong increase of MVS. In combination with the reduced MVD, this could result only in a fractional reduced perfusion which might be an explanation for the lower occurrence of BP-ONJ in patients receiving ibandronate compared to patients receiving pamidronate or zoledronate.     

Incidence of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients taking bisphosphonates for osteoporosis treatment—a grossly underestimated risk?

Purpose

The aim of this study was to detect the incidence of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in association with osteoporosis in 2009 in the rural district of Marburg-Biedenkopf, Germany. In addition, the therapeutic regimen of dentists in this area was compared to the treatment guidelines of established international associations.

Methodology

A postal survey including 129 dental offices within the named investigation area was conducted. Additionally, the dentists were asked to contribute to this study during a course of retraining. Ultimately, 107 colleagues participated in this study.

Results

A total of 37 BRONJ cases were revealed, 37.4 % of those were linked to malignant diseases, 62.6 % to osteoporosis. Noticeably, 30.1 % of the BRONJ cases linked to osteoporosis were connected with intravenous application. In total, 62.6 % of all cases were associated with intravenous and 37.4 % with oral application. Considering the estimated number of 1.014 patients using bisphosphonates for osteoporosis treatment in Marburg-Biedenkopf in 2009, the specific incidence of BRONJ could be narrowed down to about 2.27 %. In proportion to the increasing risk potential of the three patient groups, participants conducted fewer surgical interventions themselves but tended to refer patients to colleagues.

Conclusion

This study reveals the incidence of BRONJ in association with osteoporosis as being grossly underrated so far, especially in connection with intravenous bisphosphonate treatment. The therapeutic regimen of the dentists who participated correlated with the established guidelines.

Clinical relevance

The interface between dentistry and medicine may profit from our study’s results which will help to improve interdisciplinary communication. With regard to this, we wish to contribute to an informative discussion since a main focus was to ensure colleagues in their decision making, especially in case of complications after elective dentoalveolar surgery—like implantations. Besides medical there are also economic and political aspects, i.e. the financial responsibility in case of unexpected or inevitable complications, possibly leading to BRONJ, that may become part of future discussions based on this study.     

Can children be affected by bisphosphonate-related osteonecrosis of the jaw? A systematic review

Knowledge of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is mostly based on adult cases, however bisphosphonates are also currently recommended for different paediatric diseases resulting in osteoporosis. The aim of this study was to review the literature on the risk of developing BRONJ in children and adolescents. The PubMed, LILACS, Web of Science, Scopus, and Cochrane databases were searched using the key words “bisphosphonates”, “osteonecrosis”, “jaw”, and “children”. Literature reviews, case reports, abstracts, theses, textbooks, and book chapters were excluded. Studies involving children and young adults (younger than 24 years of age) were included. A total of 56 publications were identified. After applying the eligibility criteria, only seven articles remained. Although no cases of osteonecrosis were identified, all studies had weaknesses such as a limited sample size or the absence of risk factors for the development of osteonecrosis. There is general consensus that this subject should be of concern and that further studies should be conducted before any definitive opinion is reached. It is believed that patients with secondary osteoporosis who use bisphosphonates continuously should be followed up during adulthood, since bone turnover decreases over the years.     

Dental risk factors for osteonecrosis of the jaws: a CONDOR case–control study

Background

Reports of osteonecrosis of the jaw (ONJ) have associated this lesion to treatment with bisphosphonates (BPs) and dental procedures. In this study, we investigated the association of specific dental diagnoses and procedures with ONJ among patients with past BP use.

Methods

Dentists from three practice-based research networks provided ONJ cases and controls (1:3). Data gathered from patients and dental offices with two respective standard questionnaires included demographic, medical, pharmaceutical, and dental information. Diagnoses and procedures up to 3 years prior to ONJ (prior to interview for controls) were analyzed within risk strata, defined by BP use and cancer status, using interaction terms within conditional logistic regression models.

Results

We enrolled 191 ONJ cases and 573 controls from 119 dental offices. Among participants who had used only oral BP, extraction was the only dental risk factor for ONJ (odds ratio (OR)?=?12, p?=?0.01). Suppuration was also more prevalent in cases (18 %) than in controls (9 %), but not statistically significant (OR?=?9, p?=?0.06). Among participants who had not used either oral or IV BP (a majority of whom received radiation therapy to the head and neck), suppuration was the only dental risk factor for ONJ (prevalence?=?34 % for cases and 8 % for controls; OR?=?7, p?=?0.01). The prevalence of extractions in this group was also higher, but not statistically significant (44 vs 10 %; OR?=?3). Limited power precludes definitive findings among participants exposed to IV BP.

Conclusions

Among patients taking oral BP, extraction was the only dental procedure associated with subsequent ONJ development

Clinical relevance

Results of this study suggest that routine dental procedures are not associated with development of ONJ in patients exposed to BPs.     

In vitro effects of acid challenge on incisal/occlusal cupping/cratering

Statement of problem

The cause of occlusal/incisal cupping/cratering (depressed dentin surrounded by elevated rims of enamel) has been postulated to be primarily the effect of acid on exposed dentin. It is hypothesized that abrasion, bruxism, attrition, and stress-corrosion may play a secondary role in lesion formation. The primary cause and sequence of occlusal/incisal cupping/cratering remain scientifically controversial.

Bisphosphonate-related osteonecrosis of the jaws – Characteristics,risk factors,clinical features,localization and impact on oncological treatment

IntroductionOsteonecrosis of the jaw (ONJ) is a serious side-effect of intravenous nitrogen-containing bisphosphonate therapy frequently used in the treatment of malignant diseases. Despite numerous case series published so far studies with detailed investigations into risk factors, the precise localization of ONJ and impact of ONJ on the oncological treatment remain sparse.Patients and methodsThis single-centre study collated medical records (2003–2009) of all patients that suffered from ONJ within the Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Germany. In total, 126 patients fulfilled the case criteria of ONJ and were examined clinically. The complete medical history including detailed questionnaires was collected of 66 patients, focussing in particular on the identification of underlying risk factors, clinical features, ONJ localization as well as the impact on the oncological treatment.ResultsThe majority of ONJ cases occurred in patients suffering from malignant diseases (n = 117; 92.8%), in particular breast cancer (n = 57; 45.2%), multiple myeloma (n = 37; 29.4%) and prostate cancer (n = 13; 10.3%), all received nitrogen-containing bisphosphonates intravenously. ONJ was also diagnosed in 9 patients (7.1%) suffering from osteoporosis or rheumatoid arthritis. The most prevalent clinical feature was exposed necrotic bone (93.9%) in the oral cavity which was accompanied in 78.8% of cases by pain. A predilection for the mandible and in particular for molar and premolar regions in both jaws was shown. Although no recommendation concerning the oncologic treatment was made, the manifestation of ONJ resulted (in a significant proportion of the patients) in a change of medication and schedule. The most frequent co-medications were steroids and anti-angiogenetic drugs, such as thalidomide.DiscussionThe predilection for mandibular molar and premolar regions, and the infectious conditions that often precede the onset of ONJ support recent pathogenesis theories stating that local inflammation and associated pH-changes may trigger the release and activation of nitrogen-containing bisphosphonates ultimately resulting in necrosis.ConclusionThe development of ONJ has a multi-factorial aetiology and the clinical presentation can vary markedly. ONJ cannot only impair the quality of life but also the treatment of the underlying disease.     

Zoledronic acid – Related osteonecrosis of the jaws. Experimental model with dental extractions in rats

IntroductionBisphosphonate-related osteonecrosis of the jaws (BRONJ) is a pathologic condition of increasing frequency, with a poorly understood pathophysiology and which can be difficult to manage.The aim of this study was to find a reproducible experimental model that directly relates chronic bisphosphonate administration with the development of osteonecrosis with or without tooth extraction, with no other drug involved.Material and methodsTwenty male Wistar rats were divided into 4 groups (n = 5/group). Animals were injected over 9 weeks with zoledronic acid (0.1 mg/kg). In groups 1 and 2 three times a week intraperitoneally, and in group 3 once a week intravenously. A control group (group 4) received intraperitoneal injections of saline solution three times a week. After 8 weeks of treatment, 3 right upper jaw molars were extracted in groups 1, 3 and 4 and all rats were sacrificed 1 week later. The maxillae were histologically analyzed for presence of osteonecrosis foci, number of osteoclasts, vascularity, bone resorption status and presence of abscess. Radiographic examination was performed with a plain radiograph of each hemi-head.ResultsWe found that group 1 (dental extractions and highest cumulative dose of zoledronic acid) had the highest incidence of osteonecrosis (80%), absence of bone resorption (100%) and lowest number of osteoclasts (mean 7.9/field at 40×). Zoledronic acid-treated groups showed variable degrees of osteosclerosis and trabecular disorganization on X-ray study.ConclusionsWe offer a new animal model of BRONJ after zoledronic acid administration and dental extractions, achieving bone changes similar or superior to previous studies, highlighting the dental extraction as an important trigger factor.     

Radiologic bone loss in patients with bisphosphonate-associated osteonecrosis of the jaws: a case–control study

Objectives

Most patients with bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) report a previous tooth extraction at the necrosis site before the diagnosis was made. At older ages, most teeth are extracted due to periodontal disease, which is per se another BP-ONJ trigger factor. The aim of this study was to evaluate the periodontal status of BP-ONJ patients using panoramic radiographs compared to a control.

Materials and methods

All patients treated for BP-ONJ up to January 1, 2010 comprised the study. The very first panoramic radiograph was analyzed. The number of remaining teeth and the radiographic bone loss from the cemento-enamel junction to the crestal bone were measured. For each patient, one control was analyzed (matching for gender and age).

Results

One hundred twenty-nine BP-ONJ panoramic radiographs and 129 controls were analyzed (68 women, 61 men; 67.3?±?9.7 years; osteoporosis [n?=?11], breast cancer [n?=?33], multiple myeloma [n?=?61], prostate cancer [n?=?24]). The average number of remaining teeth was 12.9?±?8.4 for BP-ONJ and 16.4?±?9.4 for the control (p?=?0.02). The average radiographic bone loss was 5.5?±?2.3 mm for BP-ONJ and 3.1?±?1.1 mm for the control (p?<?0.001); 96.6 % of BP-ONJ and 77.5 % had radiographic bone loss of more than 5 mm. Radiographic bone loss in the molar region was the highest for both groups (BP-ONJ 6.0?±?2.3 mm; control 3.6?±?1.4 mm).

Conclusion

Prevalence and severity of periodontal disease in patients with BP-ONJ is higher compared to healthy controls.

Clinical relevance

Patients with periodontal disease might be at a higher risk of developing BP-ONJ; therefore, periodontal disease therapy in patients who are about to receive bisphosphonates should be undertaken.     

In vivo study of the effectiveness of quantitative percussion diagnostics as an indicator of the level of structural pathology of teeth after restoration

Statement of problem

Conventional diagnostic aids based upon imagery and patient symptoms do not indicate whether restorative treatments have eliminated structural pathology.

In situ infrared spectroscopy of the semiconductor ∣ electrolyte interface

Infrared spectroscopy has been developed as a powerful tool for the in situ study of the electrochemical interface. The possibility of using a multiple-internal-reflection geometry makes it especially suitable for the study of the semiconductor ∣ electrolyte interface. For high sensitivity to surface species, it is implemented as a differential or a modulation technique. Absorption due to vibrational transitions provides straightforward characterisation of the changes in the chemical state of the surface (interfacial films, adsorbed species, structure of the double layer); it can also be used to probe the composition of the electrolyte in the diffusion layer (redox species, reaction intermediates, pH) or even of the bulk of the electrode, in the case of intercalation reactions. Electronic absorption provides direct information on the semiconductor space-charge layer and on electronic states at the interface. Inherent possibilities of the infrared technique include the use of the polarisation of the infrared light, which gives information on the orientation of interface species, and the analysis of the time response of the infrared absorption, which gives direct information on the interfacial kinetics. Careful analysis of the changes in electrolyte absorption and spectrum baseline may provide valuable indirect information, for instance about infrared non-active species, surface roughening, or the formation of a porous layer at the interface. In situ infrared spectroscopy clearly offers a wealth of information about the semiconductor ∣ electrolyte interface, and it is sufficiently convenient and versatile that it could be used to a much wider extent than has been the case so far.     

Effect of different doses and durations of teriparatide therapy on resolution of medication-related osteonecrosis of the jaw: A randomized,controlled preclinical study in rats

Objective

To evaluate the effects of different doses and durations of teriparatide therapy on MRONJ resolution in rats.

Effectiveness of treatments for medication-related osteonecrosis of the jaw: A systematic review and meta-analysis

Background

The effectiveness of management strategies used for the treatment of medication-related osteonecrosis of the jaw (MRONJ) remains poorly understood. The authors evaluated systematically the effectiveness of the various treatment modalities used for MRONJ.

Is segmental osteotomy of the jaws outdated?

In earlier days segmental osteotomies had a broad field of indications. In the era of combined surgical-orthodontic treatments, they are pushed far into the background. This article shows that this development is unjust. If carefully indicated, segmental osteotomies still have a well-defined place in our armory of surgical interventions. With their elegance and the compulsion to respect detail they are not only of marked didactic value, but they also fill a gap, especially in the treatment options for the lower jaw. Far from being obsolete, they should still belong to the routine options when orthognathic surgery is considered.     

Computerized optical impression making of edentulous jaws – An in vivo feasibility study

PurposeWithin the specialty of prosthodontics, oral impressions are ubiquitous tools utilized to transfer intraoral characteristics such as teeth, implants, and soft tissue into a physical state (stone cast) that is processable in a laboratory setting for the fabrication of dental restorations. In recent years, optical impression systems have become ubiquitous in clinical practice replacing the conventional method of impression making. The purpose of the present study was to evaluate the feasibility and accuracy of computerized optical impression making of edentulous jaws in an in vivo setting.Methods29 edentulous patients (27 maxillae and five mandibles) underwent conventional impressions as well as computerized optical impressions. The conventional impressions and the resulting stone casts were digitized and superimposed over the computerized/digitized optical impressions in order to obtain information on differences between the two datasets. Statistical analyses were performed to identify relevant deviations.ResultsThe overall mean difference between the stone cast, digital scans and the computerized optical scans were 336.7 ± 105.0 µm (n = 32), 363.7 ± 143.1 µm (n = 24), and 272.1 ± 168.5 µm (n = 29), respectively. The visual evaluations revealed highest deviations (≥ 500 µm) in the areas of the soft palate, the sublingual areas, and the vestibule (peripheral seal zone).ConclusionsWithin the limitations of the present study, the investigated scanners were not able currently to fully replace a conventional impression for the fabrication of a complete denture.     

Surgical treatment of 61 consecutive patients with maxillary stage 3 medication–related osteonecrosis of the jaws using a pedicled buccal fat pad

Oral and Maxillofacial Surgery - Buccal fat pad (BFP) is used for the closure of large oroantral defects caused by surgical removal of the necrotic bone in patients with medication-related...