Cases Of Bisphosphonate-related Osteonecrosis Of The Jaw Research Articles

Photobiomodulation Can Prevent Medication-Related Osteonecrosis of the Jaw Formation in Tooth Extraction Site of Rat Model.

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing.

Persistent bone resorption lacunae on necrotic bone distinguish bisphosphonate-related osteonecrosis of jaw from denosumab-related osteonecrosis

Bisphosphonate and denosumab are widely used for the treatment of osteoporosis and bone metastasis of cancer to prevent excessive bone resorption. Osteonecrosis of the jaw is a serious adverse effect of bisphosphonate or denosumab referred to as bisphosphonate-related osteonecrosis of the jaw (BRONJ) or denosumab-related osteonecrosis of the jaw (DRONJ), respectively. Since bisphosphonate and denosumab inhibit bone resorption by different mechanism, we evaluated whether these drug types result in different histopathological characteristics related to bone resorption. We histopathologically investigated 10 cases of BRONJ, DRONJ, and suppurative osteomyelitis. Paraffin sections prepared from decalcified dissected jaw bones were used for histopathological observation, second harmonic generation imaging, and bone histomorphometry. The samples were also observed by a scanning electron microscope. Numerous bone resorption lacunae were observed on the necrotic bone surface in almost all cases of BRONJ; however, such resorption lacunae were limited in DRONJ and suppurative osteomyelitis. Prominent bone resorption lacunae were also confirmed by second harmonic generation imaging and scanning electron microscopy in BRONJ, but not in DRONJ or suppurative osteomyelitis. As determined by bone histomorphometry, the number of bone resorption lacunae and the length of the erosion surface of resorption lacunae were significantly higher in BRONJ group than in the DRONJ and suppurative osteomyelitis groups. These parameters were correlated between the necrotic bones and the vital bones in BRONJ. Persistent bone resorption lacunae on the necrotic bone surface are unique to BRONJ, providing a basis for distinguishing BRONJ from DRONJ and OM in histopathological diagnosis.

Biphosphonates-related osteonecrosis of the jaw

The relationship between osteonecrosis of the jaw and bisphosphonate therapy has been described recently. Although bisphosphonates have a long list of benefits in the treatment of patients with bone metastases, an increasing number of reports describe the complication of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Bisphosphonates are synthetic analogues of pyrophosphate that inhibit bone resorption. The aetiology of BRONJ is unclear. It starts as aseptic necrosis, with a surgical procedure involving an interruption in the continuity of the oral mucosa as an obligatory precondition. Subsequently, areas of osteonecrosis occur and detach from the surrounding areas of purulent inflammation or can be removed surgically. Due to the limited treatment options, conservative treatment supported by antibiotic and surgical therapy is used. This article describes a case of BRONJ.

BİFOSFONAT KULLANIMINA BAĞLI ÇENE KEMİKLERİNDE GÖRÜLEN OSTEONEKROZ VAKALARININ MEDİKAL VE CERRAHİ TEDAVİLERİ SONRASI UZUN DÖNEM TAKİPLERİ

Amac: Bu calisman amaci bifosfonata bagli cene kemiginin osteonekrozu (Bisphosphonate Related Osteonecrosis of the Jaws [BRONJ]) tanisi konmus hastalarin, yapilan medikal ve cerrahi tedavileri sonra- sinda tedavilerinin basarisini gormek ve uzun donem takibin onemini vurgulamaktir. Gerec ve Yontem: BRONJ tanisi konulmus, altisi kadin ikisi erkek olmak uzere 8 hastanin ilac ve cerrahi tedavileri ve uzun donem klinik ve radyolojik takip sonuclari degerlendirilmistir. Ruggiero ve arkadaslari- nin olusturdugu evrelendirmeye gore vakalar evrelen- dirilmis ve tedavileri yapilmistir. Hastalarin ucu osteo- poroz (biri intravenoz, ikisi oral yoldan), kalan besi malignite (intravenoz yoldan) nedeneniyle bifosfonat kullanmaktadir. Bulgular: Hastalar 8 ila 43 ay arasinda degisen, ortalama 23.8 aylik sureyle bifosfonat grubu ilac almislardir. Hastalarin ortalama yaslari 61.2 ve tedavi sonrasi ortalama takip sureleri ise 12.5 aydir. , 8 vakanin besi evre 3, diger ucu ise evre 2 olarak deger- lendirilmistir. Evre 3 hastalarin hicbirinde, medikal ve cerrahi tedavi sonrasi belirtilen takip suresince klinik ve radyolojik olarak BRONJ rekurrensi gorulmemistir. Evre 2 vakalarda ise ilac tedavisi sonrasi hastalik semptomatik olarak kontrol altina alinmistir. Sonuc : Sonuc olarak uygulanan bu tedavi protokolu ve bu calismaya dahil edilen vakalardan elde edilen veriler, cerrahi tedavinin gerektiginde uygun zamanda yapilmasinin onemini guclendirmistir. Ayrica hiperbarik oksijen tedavisinin BRONJ vakalarinda yardimci tedavi yontemlerinden biri olarak dusunulebilecegi soylene- bilir. Bifosfonat kullanim nedenleri hastalarin cerrahi ya da medikal yolla tedavi edilmelerinde direkt olarak etkili olmamistir. Anahtar kelimeler: Bifosfonat, cene osteonekrozu, hiperbarik oksijen tedavisi LONG TERM FOLLOW UP OF PATIENTS WITH BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAWS AFTER MEDICAL AND SURGICAL TREATMENT ABSTRACT Aim: The aim of this study is to observe the success of medical and surgical treatment of the patients who have been diagnosed as the bisphosphonate related osteonecrosis of the jaws (BRONJ) and emphasize the importance of long term follow up of these patients. Material and Methods: The medical and surgical treatments and long term clinical and radiological follow ups of 8 BRONJ cases, of whom 6 women and 2 men, were evaluated in this study. All cases were staged according to a staging system that was imple- mented by Ruggiero et al. and treated accordingly. Three of the patients (one intravenously and two orally) were on bisphosphonate due to osteoporosis and five of them (intravenously) due to malignant diseases. Results: Patients were on bisphosphonate for an interval of 8 to 43 months with a mean time period of 23.8 months. The mean age of the patients was 61.2 and the mean postoperative follow up time was 12.5 months. According to Ruggiero et al BRONJ staging, 5 of 8 cases were at stage-3 and the rest of them were at stage-2. None of the stage-3 cases that were treated medically and surgically showed any BRONJ recurrence clinically and radiographically during their follow up periods. Also, all three stage-2 BRONJ cases were kept under control symptomatically with medical treatment protocol. Conclusion: As a conclusion, the treatment protocol and outcome data of this study on BRONJ cases have reinforced the importance of surgical treatment that is performed at an appropriate time. Also it is possible to emphasize that hyperbaric oxygen treatment can be an adjuvant treatment method for BRONJ cases. The reason of bisphosphonate usage of these patients did not directly have any effect on either they treated surgically or medically. Key Words: Bisphosphonate, jaw osteonecrosis , hyperbaric oxygen treatment

Co-Presence of Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Squamous Cell Carcinoma in a Patient with Postmenopausal Osteoporosis: A Role for Chronic Traumatism?

Introduction:Postmenopausal osteoporosis is an important global issue. The treatment generally includes the administration of antiresorptive agents, bisphosphonate (BP) or denosumab. The most reported adverse reaction to BP is the Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ). We report a case of BRONJ in an osteoporotic patient, who simultaneously revealed an oral squamous cell carcinoma (OSCC). Case report: A 84-year-old Caucasian female referred to our Department complaining of acute pain of one month’s duration on the gingival,to the right side of the mandible. The patient had a history of post-menopausal osteoporosis treated with perosalendronate for 15 years. Clinical examination surprisingly also revealed the suspect of the contemporary presence of OSCC, that was confirmed by radiological features and histopathology. Conclusion: Unlike BRONJ or gastrointestinal damage associate to oral BP, oral ulcerations related to BP are not widely known. There is no clear evidence supporting the role of BP in the development of OSCC, but some cases of OSCC in patients taking BP are reported in literature. It would be prudent to screen and monitor these patients for all adverse reactions that could interest the oral cavity.

Uncertainty of current algorithm for bisphosphonate-related osteonecrosis of the jaw in population-based studies: a systematic review.

To assess the relevance of previous epidemiologic studies on bisphosphonate-related osteonecrosis of the jaw (BRONJ), we first conducted a systematic review of large population-based observational studies and evaluated the validity of claims-based algorithms for the identification of BRONJ. Studies containing primary observational epidemiologic data regarding bisphosphonate (BP) exposure and outcomes of osteonecrosis of the jaw were systematically reviewed. Using surrogates for identifying potential BRONJ cases from a population-based hospital registry, validation was performed through medical chart review. Positive predictive value (PPV) was estimated for each diagnostic code and for the overall algorithm utilized. Various strategies to increase PPV were also performed. Seventeen studies were systematically reviewed and presented with variations in study quality as well as inconsistent findings. Moreover, there was a high level of methodological heterogeneity. A total of 1920 patients were identified through the ICD-10 algorithm with potential BRONJ, although only 109 cases were confirmed, corresponding to an overall PPV of 5.68% (95% confidence interval [CI] 4.68-6.81). Only K10.2 (inflammatory conditions of the jaw) exhibited a relatively high PPV of 26.18%, which increased to 74.47% after confinement to BP users. Other strategies to increase PPV value were not effective. Our findings showed that the overall PPV for BRONJ identification was very low, indicating low validity of the current algorithm and possible overestimation of ONJ occurrence. There is an urgent need to develop more reliable and specific operational definitions for the identification of BRONJ cases in large population databases. © 2016 American Society for Bone and Mineral Research.

Evaluation of the predisposing factors and involved outcome of surgical treatment in bisphosphonate-related osteonecrosis of the jaw cases including bone biopsies.

ObjectivesThis study examined the statistical relevance of whether the systemic predisposing factors affect the prognosis of surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). All cases had undergone bone biopsies to determine the characteristics of the mechanisms of BRONJ by optical microscopy.Materials and MethodsThe data included 54 BRONJ cases who underwent surgery and in whom bone biopsies were performed. The results of surgery were evaluated and the results were classified into 3 categories: normal recovery, delayed recovery, and recurrence after surgery. The medical history, such as diabetes mellitus, medication of steroids, malignancies on other sites was investigated for an evaluation of the systemic predisposing factors in relation to the prognosis. The three factors involved with the medication of bisphosphonate (BP) were the medication route, medication period, and drug holiday of BP before surgery. The serum C-terminal cross-linking telopeptide (CTX) value and presence of microorganism colony in bone biopsy specimens were also checked. Statistical analysis was then carried out to determine the relationship between these factors and the results of surgery.ResultsThe group of patients suffering from diabetes and on steroids tended to show poorer results after surgery. Parenteral medication of BP made the patients have a poorer prognosis after surgery than oral medication. In contrast, the medication period and drug holiday of BP before surgery did not have significance with the results of surgery nor did the serum CTX value and presence of microorganism colony. Necrotic bone specimens in this study typically showed disappearing new bone formation around the osteocytic lacunae and destroyed Howship's lacunae.ConclusionAlthough many variables exist, this study could in part, predict the prognosis of surgical treatment of BRONJ by taking the patient's medical history.

A Model for Osteonecrosis of the Jaw with Zoledronate Treatment following Repeated Major Trauma.

This study aims to develop a reproducible rat model for post-traumatic bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our previous studies using dental extraction as an inducing factor, only 30% - 60% of zoledronate-treated animals fulfilled the definition of clinical BRONJ. We modified the zoledronate regimen and introduced repeated surgical extraction to illicit quantifiable BRONJ in all animals. Eighty retired-breeder female Sprague-Dawley rats were divided between the treatment (IV zoledronate; 80 μg/kg/week for 13 weeks) and control (saline) groups. On week 13, the left mandibular first molar was surgically extracted, followed by the second molar a week later. Animals were euthanized at 1-week, 2-weeks, and 8-weeks following extraction. The occurrence and severity of BRONJ were scored in each animal based on gross and MicroCT analysis. Parameters of bone formation and osteoclast functions at the extraction site were compared between groups. All zoledronate-treated animals developed a severe case of BRONJ that fulfilled the clinical definition of the condition in humans. Osteoclast attachment continued to be defective eight weeks after stopping the treatment. There were no signs of kidney or liver toxicity. Our data confirmed that repeated surgical extraction (major trauma) by itself consistently precipitated massive bone necrosis in ZA-treated animals, eliminating the need to induce pre-existing infection or comorbidity. These results will be the basis for further studies examining the in-vivo pathogenesis and prevention of BRONJ.

Standardized classification unsuitable for spontaneous reporting: the example of osteonecrosis of the jaw

Objective: This study assessed the impact of using a standardized definition of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the analysis of a spontaneous reporting database.Methods: All notifications of osteonecrosis of the jaw (ONJ) in the French National Pharmacovigilance Database as of 31 December 2013 were analyzed. First, we considered all reports of ONJ with bisphosphonates as BRONJ. Second, we applied the 2014 definition of BRONJ from the American Association of Oral and Maxillofacial Surgeons (AAOMS), retaining only bisphosphonates as antiresorptive medication. In the absence of any one of these criteria, or missing data, cases were not considered as BRONJ.Results: The first analysis found 158 cases of ONJ, among which 153 were associated with bisphosphonate use. The second analysis identified only 43 cases of BRONJ (28.1%).Conclusion: The definition of BRONJ as laid down by the AAOMS is not suitable for use in spontaneous reporting database. The use of the AAOMS definition alone should be avoided, as it leads to the exclusion of over 70% of cases. When cases of ONJ are identified, all results should be presented including confirmed and excluded cases.

Epidemiology, Pharmacology and Clinical Characterization of Bisphosphonate-related Osteonecrosis of the Jaw. A Retrospective Study of 70 Cases

Background and objectivesBisphosphonates are widely prescribed drugs whose principal capacity is inhibiting the osteoclast function. In 2003 a complication related to their administration, bisphosphonate-related osteonecrosis of the jaw (BRONJ), was described. The objectives of this study were to identify diagnosed cases of BRONJ in a third-level hospital over 8 years, evaluating the main features in relation to the disease, the bisphosphonate and the presence of local or general risk factors that could trigger the BRONJ. MethodsPatients diagnosed with BRONJ in a center of reference for a population of 1100000 inhabitants were selected. Variables analyzed were classified into 3 groups: patients, bisphosphonate (focusing on dose and weighting dose/potency) and osteonecrosis. ResultsSeventy cases were studied, 44 women and 26 men, with a mean age of 66.8 years. Eighteen patients received bisphosphonates orally and 52, intravenously. The mean time of administration was 26.53 months. In 67.1% of the patients it was possible to identify a local trigger, with the most common being tooth extraction (48.6%). Bone exposure was present in 89.2% of the cases, while 12 patients developed BRONJ without exposed bone, with only pain and/or chronic sinus tracts. Complete resolution was achieved in 58.6% of the patients, with a mean time of control of 16.28 months. Conclusions25% of the BRONJ cases were related to the administration of oral bisphosphonates, especially alendronate. Zoledronic acid was the bisphosphonate that required the fewest milligrams to induce osteonecrosis. Single bone exposure was the most common clinical finding, especially in the molar mandibular region in patients with metastatic disease.

Bisphosphonate-related osteonecrosis of the jaw cases

Bisphosphonate-related osteonecrosis of the jaw cases

Effects of alendronate and pamidronate on apoptosis and cell proliferation in cultured primary human gingival fibroblasts.

Data arising from the recent literature directed the researchers to study on the degree and extent of bisphosphonate toxicity on oral mucosa in further detail. The aim of this study is to determine the half maximal inhibitory concentration of pamidronate (PAM) and alendronate (ALN) on human gingival fibroblasts in vitro using 3-[4.5-thiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) assay and to evaluate the effects of both agents on the proliferation and apoptotic indices. Cells used in the study were generated from human gingival specimens and divided into alendronate (n = 240), PAM (n = 240), and control groups (n = 60). Based on the MTT assay results, 10(-4), 10(-5), 10(-6), and 10(-7) M concentrations of both drugs were administered and the effects were evaluated for 6, 12, 24, 48, or 72 h periods. An indirect immunofluorescence technique was used to evaluate apoptotic (anti-caspase 3) and proliferation (anti-Ki67) indices. Toxicity of both PAM and ALN was found to be the most potent at 10(-4)-10(-5) M range. The apoptotic index of PAM group was found to be significantly higher than ALN group for all concentrations especially at 24 h incubation time (p < 0.05). The decrease in the proliferation index was found similar in first 48 h for both drugs; however, after 72 h of incubation decrease in proliferation index in PAM group was found to be significantly higher (p < 0.05). Micromolar concentrations of not only PAM but also ALN rapidly affect cells generated from human oral gingival tissue by inducing apoptosis together with inhibition of proliferation. Cytotoxic effects of both ALN and PAM on primary human gingival fibroblasts, which cause significant changes in apoptotic and proliferative indices as shown in this in vitro study, suggests that the defective epithelialization of oral mucosa is possibly a major factor on the onset of bisphosphonate-related osteonecrosis of the jaw cases.

Thalassaemia: The Dental Implications of Bisphosphonate Therapy

Bisphosphonates (BP) are commonly used in individuals with thalassaemia to stabilise bone remodelling. However, in recent years, evidence has emerged that bisphosphonate related osteonecrosis of the jaw (BONJ) may occur. Cases of BONJ have recently been confirmed in individuals with thalassaemia. The aim of the presentation is to detail the prevalence of BONJ, outline the presentation (exposed vs. non-exposed), describe the management strategies that have been proposed, and discuss some risk reduction strategies.

Epidemiología, farmacología y caracterización clínica de la osteonecrosis de los maxilares. Un estudio retrospectivo de 70 casos

Background and objectivesBisphosphonates are widely prescribed drugs whose principal capacity is inhibiting the osteoclast function. In 2003 a complication related to their administration, bisphosphonate-related osteonecrosis of the jaw (BRONJ), was described. The objectives of this study were to identify diagnosed cases of BRONJ in a third-level hospital over 8years, evaluating the main features in relation to the disease, the bisphosphonate and the presence of local or general risk factors that could trigger the BRONJ. Material and methodPatients diagnosed with BRONJ in a centre of reference for a population of 1,100,000 inhabitants were selected. Variables analysed were classified into 3 groups: patients, bisphosphonate (focusing on dose and weighting dose/potency) and osteonecrosis. ResultsSeventy cases were studied —44 women and 26 men—, with a mean age of 66.8years. Eighteen patients received bisphosphonates orally and 52, intravenously. The mean time of administration was 26.53months. In 67.1% of the patients it was possible to identify a local trigger, with the most common being tooth extraction (48.6%). Bone exposure was present in 89.2% of the cases, while 12 patients developed BRONJ without exposed bone, with only pain and/or chronic sinus tracts. Complete resolution was achieved in 58.6% of the patients, with a mean time of control of 16.28months. Conclusions25% of the BRONJ cases were related to the administration of oral bisphosphonates, especially alendronate. Zoledronic acid was the bisphosphonate that required the fewest milligrams to induce osteonecrosis. Single bone exposure was the most common clinical finding, especially in the molar mandibular region in patients with metastatic disease.

Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw

The administration of teriparatide (TPTD) in conjunction with periodontal care could provide faster and more favorable clinical outcomes in previously refractory bisphosphonate-related osteonecrosis of the jaws (BRONJ) cases compared to conventional dental care, combination of surgery and antimicrobial treatment. We also found that underlying vitamin D levels might influence the response to TPTD treatment. Treatment of BRONJ is quite challenging and there are no standard treatment modalities. In this retrospective, longitudinal study, we examined whether additional TPTD administration could be beneficial for the resolution of BRONJ lesions compared to conservative management, such as antimicrobial treatment with or without surgery, and also studied the factors influencing the response to TPTD. Twenty-four cases of intractable BRONJ were included: 15 subjects were assigned to the TPTD group and the other 9 subjects, who refused TPTD administration, were assigned to the non-TPTD group. All subjects in both groups continued calcium and vitamin D supplementation and the TPTD group additionally received a daily subcutaneous injection of 20 μg TPTD for 6 months. While 60.0% of the non-TPTD group showed one stage of improvement in BRONJ, 40.0% of the group did not show any improvement in disease status. In the TPTD group, 62.5% of the treated subjects showed one stage of improvement and the other 37.5% demonstrated a marked improvement, including two stages of improvement or complete healing, and there was not a single case that did not improve. The clinical improvement of BRONJ was statistically better in the TPTD group after the 6-month treatment (p < 0.05). Moreover, patients with higher baseline serum 25(OH)D levels showed better clinical therapeutic outcomes with TPTD. We observed the beneficial effects of TPTD on BRONJ, and subjects with optimal serum vitamin D concentrations seemed to reap the maximum therapeutic effects of TPTD. A prospective, randomized, controlled trial should be needed to further evaluate the therapeutic efficacy of TPTD in the resolution of BRONJ.

Does regular zoledronic acid change the bone turnover of the jaw in men with metastatic prostate cancer: A possible clue to the pathogenesis of bisphosphonate related osteonecrosis of the jaw?

To find out whether the most popular pathogenesis hypothesis of the bisphosphonate (BP) related osteonecrosis of the jaw (BRONJ) is comprehensible: (1) is there a higher bone remodeling in the jaw compared with other skeletal sites? (2) Is the bone turnover (BT) of the jaw overly altered after BP intake? (3) Are there gender- or entity-specific differences in BT before and after BP intake? Bone scintigraphies of 42 patients with prostate cancer were retrospectively analyzed (n = 21 with BP intake; n = 21 no BP). All patients received bone scintigraphy prior to the therapy and in the course of the treatment (after 12 and 24 months). Data were quantitatively analyzed using six predetermined regions of interest and compared with a breast cancer cohort. The mandible revealed a similar BT as the femur and a significant lower BT compared with the maxilla. All investigated bone regions showed no significant changes under BP administration. Inter-gender differences revealed significantly lower BT values for the prostate cancer compared with the female breast cancer cohort, changes over the course of time could not be found. The finding that the mandible revealed a significant lower BT than the maxilla and the fact that 2/3 of the BRONJ cases occur in the mandible are inconsistent with the investigated hypothesis. Furthermore, the BT in the jawbone is not overly suppressed by BP. Thus, it seems implausible that a high BT and its over-suppression play the key role in the pathomechanism of BRONJ.

Histomorphologic characteristics of bisphosphonate‐related osteonecrosis of the jaw

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a known side effect of the therapy with bisphosphonates. No specific pathologic aspects or histological features are included in the most current definition. This study investigates characteristics of BRONJ with a special emphasis on histomorphologic aspects, evaluating the role of Actinomyces spp. as well as other disease-promoting factors in a formal pathogenetic context. We investigated 23 patients (14 female, nine male; mean age: 66 ± 11.8 years) who received bisphosphonates with a gender- /age-matched control group. Tissue specimens were treated according to local standards and analyzed histologically. In 18 (78.3%) BRONJ cases, we found Actinomyces spp. colonies. Bone remodeling could be found in three specimens (13%). Eight specimens (34.8%) showed signs of epithelial proliferation. Analysis of dental treatment before the onset of BRONJ did not reveal significant differences (P > 0.20). In 10 patients (83%; P > 0.05) of the reported cases a relationship between dental treatment and the occurrence of a purulent bone necrosis could be observed. Statistically significant differences in thickness of trabeculae were detected between the two study groups (P = 0.04). This study demonstrates the important influence of the osteoblast-osteoclast balance in a histomorphologic analysis. Together with cofactors, which are able to trigger the onset of BRONJ, a new pathogenesis model was developed.

Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: A pilot study comparing fibrin rich in growth factors and teriparatide

Objectives: The aim of this study is to describe and compare the evolution of recurrent bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients treated with plasma rich in growth factors or teriparatide. Material and Methods: Two different types of treatments were applied in patients diagnosed of recurrent BRONJ in a referral hospital for 1.100.000 inhabitants. In the group A, plasma rich in growth factors was applied during the surgery. In the group B, the treatment consisted in the subcutaneous administration of teriparatide. All the cases of BRONJ should meet the following conditions: recurrent BRONJ, impossibility of surgery in stage 3 Ruggiero classification and absence of diagnosed neoplastic disease. Clinical and radiographic evolution of the patients from both groups was observed. Results: Nine patients were included, 5 in group A and 4 in group B. All the patients were women on oral bis-phosphonate therapy for primary osteoporosis (5 patients) or osteoporosis-related to the use of corticosteroids (4 patients). Alendronate was the most common oral bisphosphonate associated with BRONJ in our study (four patients in group A and two in group B). The mean age was 72,8 years in the group A and 73,5 years in the group B. All the patients from group A showed a complete resolution of their BRONJ. Only one patient in the group B showed the same evolution. Conclusions: In our series, the plasma rich in growth factors showed better results than the teriparatide in the treatment of recurrent BRONJ. Key words:Osteonecrosis, oral bisphosphonate, treatment, teriparatide, plasma rich in growth factors.

Is Bone Turnover of Jawbone and Its Possible Over Suppression by Bisphosphonates of Etiologic Importance in Pathogenesis of Bisphosphonate-Related Osteonecrosis?

The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is not completely understood. The most popular hypothesis has suggested that the bone turnover (BT) in the jawbone is greater than that in other sites and that this turnover will be overly suppressed by bisphosphonates. Using bone scintigraphy, a simple tool for the quantitative evaluation of bone metabolism and blood flow, the goals of the present study were to determine whether the rate of bone remodeling is greater in the jaw and whether the bone BT in the jaw is differentially altered after bisphosphonate intake compared with that in other skeletal sites. The bone scintigraphies of 90 female patients with breast cancer were retrospectively analyzed (n= 45 with bisphosphonate intake; n= 45 without bisphosphonate intake [control group]). All patients in the study group had undergone bone scintigraphy before therapy and during the treatment (course after 12 and 24months). The data were quantitatively analyzed using 6 predetermined regions of interest. The bone BT of the mandible was similar to that of the femur and significantly reduced compared with that of the maxilla (P < .01). None of the investigated bone regions (including the mandible and maxilla) were significantly altered after bisphosphonate administration (P > .05). The finding that the mandible had significantly lower bone BT than that of the maxilla and that two thirds of BRONJ cases occur in the mandible were inconsistent with the investigated hypothesis. Furthermore, the bone BT in the jawbone was not overly suppressed by bisphosphonates. Thus, it is unlikely that over suppression of bone BT is the exclusive causation playing a role in the pathomechanism of BRONJ.

Use of antibiotic beads in the management of bisphosphonate-related osteonecrosis of the jaw

Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ) is a severe complication described as an area of bone in the jaw that has necrosed and been exposed in the mouth for more than eight weeks in a person taking bisphosphonate. Surgical debridement or resection in combinationwith antibiotic therapy is advised to resolve the acute infection and pain as well as for long-term palliation, particularly for stage 3 cases. The use of antibiotic beads in the management of osteomyelitis, which has similar clinical features with BRONJ, has been described previously. It is hypothesized that the use of antibiotic beads may be beneficial in the management of BRONJ. Two cases diagnosed with stage 3 BRONJ were managed with the use of antibiotic beads. Treatment protocol consists of thoroughdebridement and curettage to remove infected and necrotic tissue, placement of antibiotic beads, and primary closure of the wound. Removal of the antibiotic beads is then performed after six weeks. Both cases resolved uneventfully. Results suggest that the use of antibiotic beads canbe a viable treatment option in the surgical management of stage 3 BRONJ cases. Further clinical and experimental studies are needed to elucidate the exact relationship and mechanisms involved.