Side Effect Of Bisphosphonate Therapy Research Articles

Identification of Potential Biomarkers and Small Molecule Drugs for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ): An Integrated Bioinformatics Study Using Big Data.

This study aimed to identify potential molecular mechanisms and therapeutic targets for bisphosphonate-related osteonecrosis of the jaw (BRONJ), a rare but serious side effect of bisphosphonate therapy. This study analyzed a microarray dataset (GSE7116) of multiple myeloma patients with BRONJ (n = 11) and controls (n = 10), and performed gene ontology, a pathway enrichment analysis, and a protein-protein interaction network analysis. A total of 1481 differentially expressed genes were identified, including 381 upregulated and 1100 downregulated genes, with enriched functions and pathways related to apoptosis, RNA splicing, signaling pathways, and lipid metabolism. Seven hub genes (FN1, TNF, JUN, STAT3, ACTB, GAPDH, and PTPRC) were also identified using the cytoHubba plugin in Cytoscape. This study further screened small-molecule drugs using CMap and verified the results using molecular docking methods. This study identified 3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo[d]isoxazol-6-yl) methoxy) phenyl) propanoic acid as a potential drug treatment and prognostic marker for BRONJ. The findings of this study provide reliable molecular insight for biomarker validation and potential drug development for the screening, diagnosis, and treatment of BRONJ. Further research is needed to validate these findings and develop an effective biomarker for BRONJ.

EXTENSIVE OSTEONECROSIS OF THE MANDIBLE CAUSED BY BISPHOSPHONATES IN PATIENT AFTER PROSTATE CANCER TREATMENT

Osteonecrosis of the jaws is one of the most important side effects of bisphosphonate therapy. We report a case of an extensive and relapsing mandibular osteonecrosis in a male patient, 78 years old, who was referred with painful symptoms associated with extense ulcer in alveolar ridge. The patient had previous history of osteonecrosis after dental extractions, which had already been treated by bone debridement. The oral exam showed an extensive area of necrotic mandibular bone and ulcered oral mucosa. The patient reported use of bisphosphonate for 9 months in 2015 and prostate cancer chemotherapy 2 years ago. The panoramic radiograph showed an osteolytic area in anterior region of the mandible. It was performed removal of the necrotic area and mandible resection, followed by the put of a 2.4 mm biangulated reconstruction plaque. Currently, the patient is without pain or signs of relapse.

Synthetic Hydroxyapatite Inhibits Bisphosphonate Toxicity to the Oral Mucosa In Vitro.

Medication-related osteonecrosis of the jaw (MRONJ) is a side effect of bisphosphonate therapy, characterised by exposed necrotic bone. The soft tissues of the oral mucosa no longer provide a protective barrier and MRONJ patients experience pain, infections and difficulties eating. We hypothesised that hydroxyapatite (Ca5(PO4)3(OH)) could reduce bisphosphonate concentrations and protect the oral mucosa by exploiting bisphosphonate’s calcium binding affinity. The effect of zoledronic acid (ZA) and pamidronic acid (PA) on the metabolism of oral fibroblasts, oral keratinocytes and three-dimensional oral mucosa models was investigated and then repeated in the presence of hydroxyapatite granules. Without hydroxyapatite, ZA and PA significantly reduced the metabolic activity of oral cells in a dose-dependent manner. Both drugs reduced epithelial thickness and 30 µM ZA resulted in loss of the epithelium. Hydroxyapatite granules had a protective effect on oral cells, with metabolic activity retained. Oral mucosa models retained their multi-layered epithelium when treated with ZA in the presence of hydroxyapatite granules and metabolic activity was comparable to controls. These results demonstrate hydroxyapatite granules protected oral soft tissues from damage caused by bisphosphonate exposure. Porous hydroxyapatite granules are currently used for socket preservation and this data suggests their potential to prevent MRONJ in at-risk patients.

Suspected bisphosphate-related osteonecrosis of the jaw in a cat being treated with alendronate for idiopathic hypercalcaemia

An 8-year-old female neutered domestic shorthair diagnosed with idiopathic hypercalcaemia and undergoing weekly treatment with alendronate presented to Davies Veterinary Specialists for progressive facial swelling and discomfort 12 months after...

Bisphosphonate-associated Osteonecrosis of the Jaws: a Survey of the Level of Knowledge of Dentists about the Risks of Bisphosphonate Therapy.

Bisphosphonate-associated osteonecrosis of the jaws (BAONJ) is a side effect of treatment with bisphosphonate (BP). Reports of this complication have increased recently. To evaluate the level of knowledge of dentists from Plovdiv, Bulgaria, about possible complications of bisphosphonate therapy of patients in dental practice. Three hundred and twenty-three dental practitioners from Plovdiv, Bulgaria, took part in an anonymous survey containing 25 questions, designed to evaluate the knowledge of dentists about the complications of BP therapy. Oral and maxillofacial surgeons have the best knowledge about the indications and side effects of BP therapy, while dentists with a specialty in Pediatric Dentistry and General Dentistry have insufficient knowledge. Of the respondents, 17.03% are absolutely uninformed about BP and their side effects, and 1/2 declare that they have never had a patient with complications from BP therapy in their practice, probably due to a lack of awareness of the problem. Approximately half of the dentists we surveyed agree to carry out prophylactic examinations of patients receiving BP and know what the prophylactic examination includes. Only 15.48% of the respondents have correctly responded that in order to be treated as clinically healthy, patients should have stopped taking BP for more than 10 years. With the exception of specialists in Oral and Maxillofacial Surgery, dental practitioners in Plovdiv and the region are poorly informed about the complications associated with BP therapy. Therefore, efforts must be made to make these dentists better informed about BAONJ, especially about the methods and means of preventing this condition.

A novel function of geranylgeraniol in regulating testosterone production.

Isoprenoids play widely differing roles in various physiological processes in animals and plants. Geranylgeraniol (GGOH) is an isoprenoid found in plants, and is an important metabolic derivative in the isoprenoid/cholesterol synthesis pathway. Earlier studies focused on GGOH's ability to improve the side effects of bisphosphonate therapy by regulating the mevalonate pathway. More recently, the mevalonate pathway-independent effects of GGOH have been described, including anti-inflammatory, anti-tumorigenic, and neuroprotective activities. It is noteworthy that GGOH regulates the steroidogenesis pathway in testis-derived I-10 tumor cells. Testosterone is a hormone produced via steroidogenesis in testicles and plays a role in fetal development and the male reproductive system. GGOH enhanced testosterone and progesterone (its precursor) levels in I-10 cells by activating adenylate cyclase via cAMP/PKA signaling, without altering phosphodiesterase activity. These findings highlight the potential benefits of GGOH as a therapeutic agent for low testosterone levels, such as late-onset hypogonadism in men.

Angiogenesis in the Development of Medication-Related Osteonecrosis of the Jaws: An Overview.

Medication-related osteonecrosis of the jaws (MR-ONJ) is one of the most relevant side effects of bisphosphonate therapy; it is clinically defined as a non-healing wound in combination with an avascular and necrotic jaw within ongoing bisphosphonate therapy or after completed bisphosphonate therapy. Different theories concerning the development of MR-ONJ have been reported, while the exact pathophysiology is still unknown. Recent studies have increasingly focused on angiogenesis and revascularization concerning MR-ONJ pathophysiology, which seems to be a relevant factor in the development of MR-ONJ and a possible and promising point of action for MR-ONJ prevention and therapy. Therefore, and with respect to the different aspects and specific forms of angiogenesis, the enclosed review summarizes the possible role of angiogenesis and revascularization in the pathophysiology of MR-ONJ. Special focus is given to the strong negative influence of bisphosphonates on progenitor and mature endothelial cells in vitro as well as on microvessel sprouting in vitro and in vivo, which might result in overall reduced wound healing of oral soft and hard tissues, and therefore in an exposed and avascular jaw from a clinical viewpoint. Further, it will be summarized whether and in what way the aspect of angiogenesis might be used for possible MR-ONJ prevention and therapy.

Odontoiatric perspectives and osteonecrosis of the jaw as a possible adverse effect of bisphosphonates therapy in fibrous dysplasia and McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is characterized by the triad of polyostotic bone fibrous dysplasia (PFD), endocrine disorders, and café-au-lait skin pigmentation. Ninety percent of MAS patients have fibrous dysplasia (FD) craniofacial lesions. Osteonecrosis of the jaw (ONJ) has been described as an adverse side effect of bisphosphonate therapy. The aim of the study was to investigate evidence of clinical and/or radiological signs of ONJ in FD/MAS pediatric patients due to bisphosphonate therapy and describe odontoiatric tools in this population. Thirteen FD/MAS patients were enrolled. All patients during pediatric age have been treated with pamidronate infusions. They underwent complete oral clinical examination. Ortopantomography and/or CT were evaluated in all cases. No patient developed ONJ. None of them showed radiological signs different from jaw FD. In spite of the low number of patients enrolled, results confirm that, in this population, ONJ can be ruled out as a chronic adverse side effect of bisphosphonate therapy.

Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins

Osteonecrosis of the jaw (ONJ), a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA's Adverse Event Reporting System (FAERS) provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren's syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD) deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process.

Denosumab-related osteonecrosis of the jaw: a case report and management based on pharmacokinetics

Denosumab, a monoclonal antibody against the receptor activator for nuclear factor-kappa B ligand (RANKL), is a recently approved antiresorptive drug that suppresses osteoclast formation by targeting preosteclasts, in contrast to the traditional antiresorptive bisphosphonates that target mature osteoclasts. Osteonecrosis of the jaw (ONJ) is a well-known, if rare, side effect of bisphosphonate therapy; however, cases of ONJ have also been reported since 2010 in patients taking denosumab. We describe here a patient who developed ONJ while receiving denosumab; the pharmacokinetics of denosumab and bisphosphonates are discussed in the context of ONJ management.

Successful treatment of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) patients with sitafloxacin: New strategies for the treatment of BRONJ

BRONJ has become a well-known, occasionally severe side effect of bisphosphonate therapy, as well as a clinical problem. Although treatment recommendations exist, no standard therapy has yet been established for BRONJ. Also, these recommendations identify several limitations that prevent clinicians from confidently diagnosing BRONJ. The aim of the present study was to establish a treatment approach in which all patients with exposed, infected bone or intraoral/extraoral fistulas were treated with sitafloxacin (STFX). We examined 20 BRONJ patients, fourteen with cancer and six with osteoporosis. We used the current updated definition of BRONJ (12), except that we included patients who had shown symptoms for a minimum of only one month, rather than two months. Thus half of our patients had infection with no exposed, necrotic bone in the oral cavity. We purposely excluded all patients exhibiting no signs of infection (current Stages 0 and 1). In addition, each potentially causative organism was isolated from pus collected from an intraoral or extraoral fistula in ten patients on their first visit to our department. 90% of the patients had received a course of treatment with common antibiotics. STFX was administered to all patients. We then re-evaluated the lesion every other week, to determine whether epithelialization was present. We recommended surgical treatment for cases without epithelialization within 4weeks after the onset of administration of STFX even if bone was not exposed at the lesion. 19 of our 20 cases of Stages 2–3 BRONJ responded to 2–10weeks of STFX treatment by entering either a remission or healed phase. While surgery was done on thirteen cases, seven others reached such phases without surgery. Every patient had at least one bacterial species that showed resistance to common antibiotics. All species in all patients were susceptible to STFX. Our results indicate that STFX, with or without minor surgery, gives a high probability of controlling infection in BRONJ patients with persistent infection after use of common antibiotics, leading to remission and/or complete healing in 95% of patients.

The national-scale cohort study on bisphosphonate-related osteonecrosis of the jaw in Taiwan

ObjectivesOsteonecrosis of the jaw (ONJ) is a potential side effect of bisphosphonate therapy. This Taiwanese national-scale cohort study aimed to investigate its incidence and risk of development by using a qualified control group with different demographic factors (age/gender), dental (tooth extraction/periodontal therapy) and medical (jaw radiotherapy) treatments, delivery routes (oral/intravenous), and diseases (diabetes/osteoporosis/cancer). MethodsData (n=958,136) from January 1, 2006 through December 31, 2008 were sourced from the Longitudinal Health Insurance Database 2005 of Taiwan. Cases of BRONJ were identified by three criteria modified from the definition proposed by the American Association of Oral and Maxillofacial Surgeons. The Cox proportional-hazards regression model and Kaplan–Meier estimates were used to analyse the results. ResultsThe incidence densities of ONJ in the unexposed and bisphosphonate-exposed cohorts were estimated as 4.4 and 73.5 per 100,000 person-years, respectively (relative risk=16.8; 95% CI=6.0–37.5; P<0.001). Multivariate analysis revealed strong associations of delivery route, tooth extraction, and oral cancer with ONJ (hazard ratios=51.4 for oral bisphosphonates, 153.3 for intravenous bisphosphonates, 5.3 for tooth extraction, and 278.1 for oral cancer). ConclusionsThese results not only demonstrate the incidence and relative risk of bisphosphonate-related ONJ in Taiwan but also indicate that tooth extraction and oral cancer may have a major impact on its development. Clinical significancePhysicians should be aware of individual patient risk factors before prescribing bisphosphonates. Bisphosphonate treatment is justified in the amelioration of life-threatening conditions in patients in whom ONJ would only affect quality of life.

Effect of Dental Implants on Bisphosphonate-Related Osteonecrosis of the Jaws

Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is a side effect of BP therapy. Dental implants are believed to be a risk factor for developing BRONJ. In the present study, we analyzed the interval to the development of BRONJ in patients treated with BP who had received dental implants. Patients with dental implants and established BRONJ were evaluated at the oral and maxillofacial surgery department (Medical University of Vienna). In addition, studies from 1978 to 2012 were included in a meta-analysis. Three groups were created: implantation before BP treatment, implantation after BP treatment, and implantation during BP treatment. The outcomes were evaluated using linear regression analysis. Patients who underwent dental implantation during (P < .001) and after (P < .001) treatment with BPs developed BRONJ more rapidly. The treatment duration with oral BPs was significantly related to the rapidity of developing BRONJ (P= .03). The insertion of dental implants during or after BP treatment accelerated the development of BRONJ. BRONJ occurred less frequently when the implants had been inserted before BP therapy had been started.

Experimental investigation of relationship between trauma and bisphosphonate-related osteonecrosis.

Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) disease is rare, but there are serious side-effects of BP therapy in patients. In some patients, surgery is needed and could not be cured. A standard test is not available showing the risk of jaw osteonecrosis in routine use. The measurement of serum C-terminal telopeptide (CTX) levels has been used in diseases of BRONJ resorption and antiresorptive therapy. This paper is aimed at investigating the relationship between traumatic procedures and presence of BP-related osteonecrosis. Thirty male Wistar albino rats with weighing 200 ± 20 g were used for the experimental procedures. Rats were randomly divided into three groups each containing 10 rats as follows: Group 1 (traumatic extraction group), Group 2 (atraumatic extraction group), and Group 3 (control group). All groups, zoledronic acid (ZA) (0.3 mg/kg/week) [1] was diluted with physiological saline and given subcutaneously for 2 months. After the 2 months, Group 1 was subjected to traumatic extraction of right first lower molars, and Group 2 was subjected to atraumatic extractions of the right first lower molars. Group 3 was subjected to no extractions as a control group. Animals were euthanized 32 days after tooth extractions, and the ZA administration protocol was maintained until the animals' death. After sacrifice, blood samples were collected for C-terminal cross-linking telopeptide of type I collagen (CTX-1) levels, clinical and radiological findings were recorded. The bone resorption marker CTX-1 showed a significant difference among the groups. CTX-1 was measured significantly higher in blood samples of Group 2 (4.15 ± 0.34; P = 0.001) than Group 1 (3.77 ± 0.34; P = 0.0001). No, statistically significant changes were found between Groups 1 and 2 as for clinical and radiological assessment. This study provides preliminary observations for the development of an animal model of BRONJ. Although clinical and radiological findings were not relevant, serum CTX values are reliable biochemical markers for predicting BRONJ and also atraumatic surgical procedures are important to prevent BRONJ.

Effect of low-level laser therapy on oral keratinocytes exposed to bisphosphonate

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate therapy. However, its pathophysiology is not yet fully elucidated, and effective treatment of BRONJ remains unclear. The aim of this study is to investigate the effects of alendronate on oral keratinocytes and of low-level laser therapy (LLLT) on alendronate-treated keratinocytes, specifically by evaluating their viability, apoptosis, and wound healing function after irradiation. Oral keratinocyte cells (HaCaT) were exposed to 25μM alendronate. Then, laser irradiation was performed with a low-level Ga-Al-As laser (λ = 808 ± 3nm, 80mW, and 80mA; NDLux, Seoul, Korea) using 1.2J/cm(2) energy dose. Viability was analyzed using MTT assay. Apoptosis was measured by Hoechst staining, caspase assay. Changes in secretion of IL-8, VEGF, and collagen type I were studied by ELISA and immunofluorescence microscopy. Scratch wound assays were also performed to measure cellular migration. Our results show that alendronate inhibits keratinocyte viability, expression of IL-8, VEGF, and collagen type I which are intimately related to healing events and cell migration while promoting apoptosis. Our results serve to demonstrate the utility of LLLT in partially overcoming the inhibitory effects of this bisphosphonate. From these results, the authors believe that the present study will provide an experimental basis for a fuller explanation of the clinical effects of LLLT as a BRONJ treatment modality.

The association between serious upper gastrointestinal bleeding and incident bisphosphonate use: a population-based nested cohort study

BackgroundOral bisphosphonates are commonly used to prevent / treat osteoporosis. However, bisphosphonate treatment is not without risk and serious adverse effects, including upper gastrointestinal bleeding (UGIB) have been described. We sought to determine if new users of bisphosphonate drugs were more likely to suffer a serious UGIB within 120 days of drug initiation.MethodsThis was a population-based nested cohort study utilizing administrative healthcare data in British Columbia, Canada. Community based individuals ≥ 65 years with a new prescription for a bisphosphonate between 1991 and 2007 were included. A multivariate logistic regression model was used to examine the relationship between older age and the development of a serious UGIB within 120 days of new exposure to oral bisphosphonate drugs.ResultsWithin the exposure cohort (n = 26,223), 117 individuals had suffered a serious UGIB within 120 days of incident bisphosphonate use. Cases tended to be > 80 years old, and were significantly more likely to have had a past history of gastric ulcer disease, a remote history of serious UGIB, and had been dispensed proton pump inhibitor (PPI) medications (p < 0.001 for all comparisons). After adjustment for confounding covariates, those > 80 years were more than twice as likely to suffer a UGIB when compared to those ≤ 80 years (adjusted OR = 2.03; 95% CI 1.40–2.94). A past history of serious UGIB was the strongest predictor of UGIB within 120 days of incident bisphosphonate use (adjusted OR = 2.28; 95% CI = 1.29–4.03) followed by PPI use (adjusted OR = 2.04; 95% CI = 1.35–3.07). Males were 70% more likely to suffer an UGIB compared to females (adjusted OR = 1.69; 95% CI = 1.05–2.72).ConclusionsUpper GIB is a rare, but serious, side effect of bisphosphonate therapy more often afflicting older individuals. At the same time, concern about potential rare adverse events should not discourage clinicians from prescribing bisphosphonate drugs, particularly in older patients who have already sustained a fragility fracture. Clinicians must remain cognizant of potential adverse events associated with bisphosphonate use and should routinely ask about pre-existing GI disorders and concurrent medication history prior to prescribing these drugs.

Lack of response to teriparatide therapy for bisphosphonate-associated osteonecrosis of the jaw

Dear Editor, Osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate therapy. Its pathogenesis is multifactorial and seems to be the combined result of attenuated osteoblastic activity due to the patient's underlying disease and inhibition of bone resorption by bisphosphonates. This leads to defective bone remodelling and a consequent impairment in the ability to repair bone damaged by oral trauma such as dental extraction or implant or to maintain bone homeostasis (some cases occur spontaneously without associated trauma) [1]. Management of ONJ is a challenge, due to the lack of effective treatment. Recently, teriparatide was reported as an adjunctive therapy for this condition. Because teriparatide is a medication that exerts anabolic effects on bone, it has been suggested that this drug might be beneficial in situations in which bone repair must be stimulated. To date, six independent case reports have documented the efficacy of teriparatide in the management of severe bisphosphonate-related ONJ resistant to conventional therapy (Table 1) [2–7]. On the basis of this preliminary evidence, we tested teriparatide in another case of bisphosphonate-associated ONJ. The patient was a 79-year-old woman with a 3-year history of rheumatoid arthritis treated with oral methotrexate (15 mg weekly), naproxen (1 g daily), prednisone (5 mg/ daily) and rituximab (the last treatment cycle with 1 g, 2 weeks apart, had been administered 6 months previously). She also had osteoporosis treated with 1,200 mg of calcium with 800 IU of vitamin D daily and ibandronate 150 mg once monthly. After 32 months of bisphosphonate therapy, the patient developed spontaneous osteonecrosis of the right mandible, without evidence of associated osteomyelitis (Fig. 1). She was evaluated by an oral and maxillofacial surgeon and treated with antiseptic mouthwashes and oral amoxicillin, since there was no indication for incision and drainage. Ibandronate was stopped and replaced by teriparatide at a dose of 20 μg per day. Unfortunately, despite treatment with teriparatide for 8 months, the patient did not present any noticeable symptomatic benefit and the mandibular osseous defect did not substantially improve on control computed tomography (Fig. 1). Previous reports [2–7] suggest that there may be a therapeutic role for teriparatide in the management of severe ONJ in patients with non-malignant skeletal disease. However, the lack of response in our case challenges this impression. J. Narvaez (*) : C. Gomez-Vaquero : J. M. Nolla Department of Rheumatology (planta 10-2), Hospital Universitario de Bellvitge-IDIBELL, Feixa Llarga s/n. 08907, L Hospitalet de Llobregat, Barcelona, Spain e-mail: fjnarvaez@bellvitgehospital.cat

Bisphosphonate-Related Osteonecrosis of the Jaws. A Severe Side Effect of Bisphosphonate Therapy

Bisphosphonates (BP) are potent inhibitors of bone resorption used mainly in the treatment of metastatic bone disease and osteoporosis. By inhibiting bone resorption, they prevent complications as pathological fracture, pain, tumor-induced hypercalcemia. Even though patient's benefit of BP therapy is huge, various side effects may develop. Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is among the most serious ones. Oncologic patients receiving high doses of BP intravenously are at high risk of BRONJ development. BPs impair bone turnover leading to compromised bone healing which may result in the exposure of necrotic bone in the oral cavity frequently following tooth extraction or trauma of the oral mucosa. Frank bone exposure may be complicated by secondary infection leading to osteomyelitis development with various symptoms and radiological findings. In the management of BRONJ, conservative therapy aiming to reduce the symptoms plays the main role. In patients with extensive bone involvement resective surgery may lead to complete recovery, provided that the procedure is correctly indicated. Since the treatment of BRONJ is difficult, prevention is the main goal. Therefore in high risk patients dental preventive measures should be taken prior to bisphosphonate administration. This requires adequate communication between the prescribing physician, the patient and the dentist.

Incidence of maxillary sinusitis and oro-antral fistulae in bisphosphonate-related osteonecrosis of the jaw

ObjectiveBisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side-effect of bisphosphonate therapy. In the majority of cases BRONJ occurs in the mandible. As a consequence a detailed investigation of BRONJ of the maxilla and in particular of involvement of the maxillary sinus has largely so far been neglected. The aim of this study was to analyse the frequency of maxillary sinusitis and oro-antral fistulae in BRONJ of the maxilla. Subjects and methodsA retrospective multicentre analysis was carried out in three Departments of Oral and Maxillofacial Surgery focussing on patients suffering from BRONJ in the maxilla. The role of involvement of the maxillary sinus, in particular sinusitis and oro-antral fistula, was analysed. ResultsOut of a total of 170 patients suffering from BRONJ 53 cases (31.2%) with involvement of the maxilla were identified. At least one sign of maxillary sinusitis was present in 43.6% (23/53) and an oro-antral fistula in the course of the disease was detected in 35.8% (19/53) of those patients. The mean length of time of bisphosphonate intake was 36.16±16.32 months. Zoledronate was most frequently associated (60.4%) with symptoms, followed by the combination of Zoledronate/Ibandronate (13.2%), and Zoledronate/Pamidronate or Pamidronate alone (both 7.5%). ConclusionMaxillary sinusitis and oro-antral fistulae are associated with a BRONJ manifestation in the upper jaw in approximately 44%. The involvement of the maxillary sinus should be given special attention and three-dimensional imaging modalities might be necessary, not only to evaluate the extent of necrosis, but also to exclude involvement of the maxillary sinus.

Osteonecrosi spontanea dei mascellari in relazione all’assunzione di bisfosfonati endovenosi: caso clinico

ObjectivesOsteonecrosis of the jaw (ONJ) is one of the multiple side effects of bisphosphonate therapy. The incidence of ONJ among patients receiving intravenous (IV) bisphosphonates exceeds that recorded in patients treated with oral bisphosphonates. We report a case of spontaneous ONJ related to intravenous administration of bisphosphonates. Materials and methodsWe describe a case of spontaneous mandibular osteonecrosis in a female patient who underwent dental surgery before beginning therapy with bisphosphonates. ResultsThe patient's bone exposure was resolved, which illustrates that prompt, effective treatment can produce cures in patients with ONJ on IV bisphosphonate therapy and with other risk factors. ConclusionsPatients scheduled to undergo IV bisphosphonate therapy should be informed of its potential risks and treated in accordance with a precise therapeutic procedure that includes a dental evaluation before treatment. This approach ensures rapid resolution of possible treatment-related complications via consultation and collaboration of various medical specialists.