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Database(s): Ovid MEDLINE(R) 1946 to February Week 2 2012

Result 1.
Title Bisphosphonate-associated osteonecrosis of the jaws -- report of three cases in Bulgaria and review of the literature. Source Abstract Acta Clinica Croatica. 50(2):273-9, 2011 Jun. A severe complication of the administration of bisphosphonate-containing medications is known as bisphosphonate-associated osteonecrosis of the jaws (BONJ). A case series of three patients affected by BONJ is presented. These patients currently represent the only described cases of BONJ in Bulgaria. Exposed necrotic bone of the mandible was observed in two patients and the maxilla was affected in the third case. Two of the patients had been treated with zoledronate for metastatic prostate cancer and one patient for metastatic endometrioid cancer. All three patients underwent surgical treatment. One of the patients received conservative surgical debridement, i.e. removal of necrotic bone only, and primary wound closure. Conservative surgical debridement and application of local medications without wound closure were used in the other two patients. All three patients received systemic antibiotic treatment. No evidence of disease progression was observed during the follow-up period of 3 to 12 months. The surgical approach utilized in the present study is discussed in the light of the etiopathogenesis, prevention and treatment of BONJ. Year of Publication 2011

Result 2.
Title Source Bisphosphonate-related osteonecrosis of the jaws. Current Opinion in Otolaryngology & Head & Neck Surgery. 19(4):302-6, 2011 Aug. Abstract PURPOSE OF REVIEW: The purpose of this article is to review a new pathologic entity named bisphosphonate-related osteonecrosis of the jaws (BRONJ). RECENT FINDINGS: BRONJ was observed and first reported in 2001-2002 when clinicians noticed cases of refractory osteomyelitis after simple dental procedures such as dental extractions in patients who had

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received bisphosphonate therapy. The condition was initially seen in patients who received i.v. bisphosphonates for malignancies such as multiple myeloma and metastatic breast cancer. However, with the use of bisphosphonate therapy for osteoporosis, BRONJ is seen in patients without a cancer diagnosis. SUMMARY: The incidence of BRONJ remains unclear. Treatment recommendations based on sound scientific data are sparse. The management of BRONJ remains a difficult and controversial situation that continues to challenge the clinician. Year of Publication 2011

Result 3.
Title Is rheumatoid arthritis a risk factor for oral bisphosphonate-induced osteonecrosis of the jaws?. Source Abstract Medical Hypotheses. 77(5):905-11, 2011 Nov. Bisphosphonate-related osteonecrosis of the jaws is a relevant sideeffect of these drugs that has been generating a great concern through increasing reports, worldwide, of this bone necrosis. Among several BRONJ hypothetical co-factors that could play a role in BRONJ pathogenesis, rheumatoid arthritis (RA) has been included as a relevant risk factor for BRONJ; however, until now the relationship between these diseases has not been fully explained. Thus, the purpose of this paper is to establish hypothetical factors that could link these two diseases, considering mainly inflammatory components and the organism effects of medicines used to treat RA, particularly steroids and methotrexate (MTX). Copyright Copyright 2011 Elsevier Ltd. All rights reserved. Year of Publication 2011

Result 4.
Title Osteonecrosis of the jaw in patients with metastatic breast cancer: ethnic and socio-economic aspects. Source Abstract Breast Journal. 17(5):510-3, 2011 Sep-Oct. Bisphosphonate therapy is an important adjunct to the treatment of patients with bone metastasis. Osteonecrosis of the jaw (ONJ), a complication related to bisphosphonate therapy, is reported in up to 7%

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of patients with metastatic breast cancer. The objective of this study was to define the prevalence and to identify risk factors associated with development of ONJ in a predominantly low socio-economic population. Medical records of patients with a diagnosis of metastatic breast cancer with bone metastasis seen between 2002 and 2007 were reviewed. All patients received a minimum of four infusions of zolendronic acid. Data on demographics, insurance status, tobacco use, concurrent therapy, body mass index, and number of zolendronic acid infusions were analyzed. Of the 110 patient analyzed, 10 developed ONJ (9%) with the mean number of zolendronic acid infusions in patients with ONJ of 22.9 +/- 17. ONJ was seen more frequently in Caucasian than in African Americans patients (15% versus 2%; p = 0.019). ONJ was associated with older age at diagnosis of metastatic breast cancer (p = 0.02), tobacco use (p = 0.049), but was not associated with SES or duration of therapy. After adjusting for SES, Caucasian patients were 9.1 times more likely to have ONJ when compared with African American patients. (95% CI 1.03-81.7). Our results suggest an increase prevalence of ONJ in Caucasian breast cancer patients. However, as our study population is small, additional studies to confirm this finding are needed. Copyright 2011 Wiley Periodicals, Inc. Year of Publication 2011

Result 5.
Title Physicians' awareness of bisphosphonates-related osteonecrosis of the jaw. Source Abstract Saudi Medical Journal. 32(8):830-5, 2011 Aug. OBJECTIVE: To assess the awareness and knowledge of physicians and dentists regarding bisphosphonates related osteonecrosis of the jaw (BRONJ). METHODS: A cross-sectional descriptive study was carried out in the Department of Dentistry, Riyadh Military Hospital, Kingdom of Saudi Arabia from June to September 2010. Data were collected through a selfadministered questionnaire distributed among a sample of physicians and dentists at the hospital. RESULTS: A total of 222 valid completed responses were obtained (response rate: 82.2%). Less than one-third of the participants (31.5%) were aware of osteonecrosis of the jaw, while slightly more than half of

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them were treating patients with bisphosphonates (BP). None of the physicians had a correct response in all 4 knowledge questions. There were statistically significant associations between knowledge and qualification (p=0.019), years of experience (p=0.002), and specialty (p=0.034). CONCLUSION: We found that physicians and dentists have low awareness and deficient knowledge regarding BRONJ, although most of them do prescribe BP to their patients. Therefore, intervention to raise awareness and knowledge among healthcare providers is needed. Year of Publication 2011

Result 6.
Title Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons. Source Abstract Journal of Rheumatology. 38(7):1396-402, 2011 Jul. OBJECTIVE: Osteonecrosis of the jaw (ONJ) in association with use of bisphosphonate (BP) has been described primarily in cancer patients receiving high-dose intravenous BP. The frequency of the condition in patients with osteoporosis appears to be low. We evaluated the frequency of BP-associated ONJ in Ontario in the cancer population and in those receiving BP for osteoporosis and metabolic bone disease. METHODS: A survey developed by representatives of the Ontario Society of Oral and Maxillofacial Surgeons was mailed to Ontario oral and maxillofacial surgeons (OMFS) in December 2006, asking oral surgeons to provide information on cases of ONJ seen in the previous 3 calendar years (2004 to 2006). OMFS were subsequently contacted by telephone if they had not responded or if they had reported cases of ONJ. The frequency of ONJ in association with BP use was estimated from the number of patients with filled prescriptions for BP in Ontario between 2004 and 2006. The cumulative incidence of ONJ was calculated separately for patients using intravenous (IV) BP for cancer treatment and for patients using oral or IV BP for osteoporosis or other metabolic bone disease. RESULTS: Between 2004 and 2006, 32 ONJ cases were identified. Nineteen patients received IV BP for cancer treatment and 13 patients received oral or IV BP for osteoporosis or metabolic bone disease. Over a 3-year period the cumulative incidence of BP-associated ONJ was 0.442%

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of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or other metabolic bone disease observations (1.04 per 100,000). The relative risk of low dose IV/oral BP-associated ONJ was 0.002 (95% CI 0.001, 0.005) compared to high-dose IV BP. Other risk factors for ONJ were present in all cases in whom detailed assessment was available. The median duration of exposure to BP was 42 months (range 36 to 120 mo) and 42 months (range 11 to 79 mo) in osteoporosis patients and cancer patients, respectively. CONCLUSION: Over a 3-year period, the cumulative incidence for BPassociated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or metabolic bone disease observations (1.04 per 100,000). This study provides an approximate frequency of BP-associated ONJ in Canada. These data need to be quantified prospectively with accurate assessment of coexisting risk factors. Year of Publication 2011

Result 7.
Title Successful treatment of advanced bisphosphonate-related osteonecrosis of the mandible with adjunctive teriparatide therapy. Source Abstract Head & Neck. 33(9):1366-71, 2011 Sep. BACKGROUND: The management of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is challenging and controversial. At present, there is no established medication treatment for the disease. METHODS: A 78-year-old osteoporotic woman with osteonecrosis of the mandible related to alendronate therapy was referred for treatment. The disease was unresponsive to conservative therapy, including antibacterial mouth rinse, antibiotics, and minor surgical debridement. Teriparatide, a human recombinant pararthyroid hormone peptide 1-34, was then used for treatment. RESULTS: The oral mucosa completely regrew, and pain subsided 4 weeks after the initiation of teriparatide administration. Progressive bone regeneration was found during and after the 6-month period of teriparatide therapy. CONCLUSION: Our case demonstrated that teriparatide can be an

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important adjuvant in the management of advanced BRONJ and should be considered prior to major resection with reconstruction. Its true value in the treatment of BRONJ for noncancer patients with osteoporosis warrants future studies. Copyright Copyright 2010 Wiley Periodicals, Inc. Year of Publication 2011

Result 8.
Title Source Abstract Bisphosphonate-related osteonecrosis of the jaws. [Review] Revista Brasileira de Reumatologia. 51(4):401-3, 407, 2011 Aug. Bisphosphonates are potent inhibitors of bone resorption, and are used in the treatment of osteoporosis and other diseases that cause bone mass loss, such as Paget's disease, bone metastases, and multiple myeloma, to prevent pathological fractures. Since 2003, avascular osteonecrosis of the jaw has been associated with the use of bisphosphonates, mainly intravenous. According to the literature, the occurrence of osteonecrosis of the jaw has ranged from 0.8% to 12% of the patients on bisphosphonates, most of them on prolonged use. Physicians and odontologists should be aware of that potential complication in dental treatment. Year of Publication 2011

Result 9.
Title Source Risk factors for bisphosphonate-related osteonecrosis of the jaws. Journal of Oral & Maxillofacial Surgery. 69(4):959; author reply 959-60, 2011 Apr. Year of Publication 2011

Result 10.
Title Source Abstract ONJ in two dental practice-based research network regions. Journal of Dental Research. 90(4):433-8, 2011 Apr. The incidence of osteonecrosis of the jaw (ONJ) in the population is low, but specifics are unknown. Potential risk factors include bisphosphonate treatment, steroid treatment, osteoporosis, and head/neck radiation. This Dental Practice-Based Research Network study estimated ONJ

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incidence and odds ratios from bisphosphonate exposure and other risk factors using a key word search and manual chart reviews of electronic records for adults aged >= 35 yrs enrolled during 1995-2006 in two large health-care organizations. We found 16 ONJ cases among 572,606 cohort members; seven additional cases were identified through dental plan resources. Among 23 cases (0.63 per 100,000 patient years), 20 (87%) had at least one risk factor, and six (26%) had received oral bisphosphonates. Patients with oral bisphosphonates were 15.5 (CI, 6.0-38.7) more likely to have ONJ than non-exposed patients; however, the sparse number of ONJ cases limits firm conclusions and suggests that the absolute risks for ONJ from oral bisphosphonates is low. Year of Publication 2011

Result 11.
Title Osteonecrosis of the jaw on imaging exams of patients with juvenile systemic lupus erythematosus. Source Abstract Revista Brasileira de Reumatologia. 50(1):3-15, 2010 Feb. OBJECTIVE: The objective of the present study was to evaluate radiographic changes of the temporomandibular joint (TMJ) in patients with juvenile systemic lupus erythematosus (JSLE) and a control group. PATIENTS AND METHODS: Panoramic radiographies of the TMJ of 26 JSLE patients and 28 healthy individuals were evaluated. Multislice computed tomography (MCT) was performed on those patients who presented flattening and/or destruction of mandibular condyles. Demographic data, oral health indices, clinical manifestations, laboratory exams, and treatment were evaluated. RESULTS: Important radiographic changes consistent with osteonecrosis of the mandible, confirmed by MCT of the TMJ, were observed in 2/26 (8%) JSLE patients versus 0% in the control group (P = 0.22). Mild clinical dysfunction and abnormal TMJ mobility were observed in 67% and 54% of the patients, respectively. Age of onset, disease duration, and current age were similar in JSLE patients with and without severe radiographic changes of TMJ (9.3 versus 10.8 years, P = 0.77; 3.3 versus 2 years, P = 0.63; 12.6 versus 13.5 years, P = 0.74, respectively). Significant differences in gender, socioeconomical status, oral health indices, clinical manifestations, laboratory exams, and treatment were not observed between both subgroups (P 0.05). Both JSLE patients with

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osteonecrosis of the mandible had active chronic disease, used corticosteroids for a prolonged period, and had mild TMJ dysfunction. Antiphospholipid antibodies were not observed in those two patients, and neither one had been treated with bisphosphonate. CONCLUSIONS: Osteonecrosis of the mandible with mild TMJ dysfunction was observed in some of the patients, demonstrating the importance of odontological assessment during clinical follow-up. Year of Publication 2010

Result 12.
Title Clinical comparison of patients with osteonecrosis of the jaws, with and without a history of bisphosphonates administration. Source International Journal of Oral & Maxillofacial Surgery. 39(11):1097-102, 2010 Nov. Abstract This retrospective study aimed to evaluate the role of bisphosphonates in jaw osteomyelitis. 29 patients were included: 18 had been treated with bisphosphonates (12 with multiple myelomas, 3 with breast carcinomas, 2 with prostate carcinomas, and 1 with osteoporosis). Of 11 control patients, 2 had breast carcinomas, 2 had bronchial carcinomas, and 7 had no cancer. Descriptive and statistical evaluations were conducted to investigate the influence of chemotherapy, corticosteroids, stem cell transplantation, and bisphosphonates on the development and clinical picture of osteomyelitis. Both groups had similar disease histories, clinical pictures, treatment methods, and outcome. Wound dehiscence frequencies were also similar (Mann-Whitney rank sum test 1.66+/-1.5 vs. 1.45+/-2.0 p=0.393). Chemotherapy, steroid therapy, stem cell transplantation, or bisphosphonate administration did not correlate with the clinical picture. Neither the duration of therapy nor the type of bisphosphonate influenced the clinical picture (negative Fisher's tests). The bisphosphonate group showed a characteristic settlement of Actinomyces in the exposed bone (positive Fisher's test, p=0.021). These results suggested that osteomyelitis developed as a consequence of the simultaneous, cumulative action of many factors. Bisphosphonates played a role comparable to other predisposing features. Coating the jaws with bisphosphonates could promote the settlement of Actinomyces. Copyright Copyright 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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Year of Publication 2010

Result 13.
Title Bisphosphonate-related osteonecrosis of the jaws: a review of 34 cases and evaluation of risk. Source Abstract Journal of Cranio-Maxillo-Facial Surgery. 38(4):255-9, 2010 Jun. INTRODUCTION: The purpose of this study was to identify factors that influence bisphosphonate-related osteonecrosis of the jaws (BRONJ). PATIENTS AND METHODS: Patients undergoing treatment for BRONJ (n=34) were evaluated. Sex, age, underlying diagnosis, type of bisphosphonate (BP), duration and route of administration, location of osteonecrosis, clinical symptoms, Actinomyces colonisation, treatment and outcome were recorded. Symptom onset was analysed with respect to BP potency and cumulative dose. RESULTS: Underlying diagnoses indicating BP-treatment included multiple myeloma, breast carcinoma, prostate carcinoma and osteoporosis. In 31 patients, BRONJ was preceded by tooth extraction, root apicotomy, illfitting dentures, cystenucleation, implant insertion or trauma; in 3 patients, the precipitating event was not identified. Actinomyces colonisation was observed in 18 patients (53%). The occurrence of BRONJ was not directly related to BP dose or potency. More women with multiple myeloma had BRONJ than did males. BRONJ was observed in osteoporotic patients treated with both corticosteroids and BPs. CONCLUSIONS: BRONJ was not primarily associated with BP potency or dose. Factors that increased the risk of osteonecrosis were female sex, oral surgery and corticosteroids plus intravenous or oral BP administration. BP deposition in the jaw bones might enhance BRONJ by promoting bacterial colonisation; however, this hypothesis requires more study. Copyright (c) 2009 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved. Year of Publication 2010

Result 14.
Title Resolution of oral bisphosphonate and steroid-related osteonecrosis of

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the jaw--a serial case analysis. Source Abstract Journal of Oral & Maxillofacial Surgery. 68(5):1055-63, 2010 May. PURPOSE: To offer recommendations of risk factors, prevention, and treatment of oral bisphosphonate and steroid-related osteonecrosis of the jaw (BSRONJ) in Taiwan. MATERIALS AND METHODS: Twelve patients were clinicopathologically proved to have bisphosphonate-related osteonecrosis of the jaw (BRONJ). All of the patients were taking oral bisphosphonates and were concurrently administered long-term steroids. Of the 12 patients, 3 patients were assigned to the first stage of BRONJ; 5 patients were assigned to the second stage, and 4 patients were assigned to the third stage. The patients' symptoms, localization of necrosis, presence of a fistula, and association with possible triggering factors for onset of the lesion were recorded. RESULTS: The radiologic investigations revealed osteolytic areas and scintigraphy demonstrated increased bone metabolism. Microbiologic analysis showed pathogenic actinomycosis organisms in a majority of patients (91.6%). Antibiotic therapy, minor debridement surgery, and combined hyperbaric oxygen therapy were useful in obtaining short-term symptomatic relief. CONCLUSIONS: Comorbidities of steroid use along with bisphosphonates may cause osteonecrosis of the jaw to occur sooner, be more severe, and respond more slowly to a drug discontinuation. The clinical disease of BSRONJ is more severe and more unpredictable to treat than BRONJ. From the data gained from other published studies of BRONJ and our clinical experience with the series of cases of BSRONJ, we offer recommendations of risk factors, prevention, and treatment of BSRONJ in southern Taiwan. Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved. Year of Publication 2010

Result 15.
Title Bisphosphonate-related osteonecrosis of the jaw associated with dental implants. Source Journal of Oral & Maxillofacial Surgery. 68(4):790-6, 2010 Apr.

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Abstract

PURPOSE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-documented devastating side effect of long-term bisphosphonate (BP) use. There is scarce information in the literature on BRONJ associated with dental implants (DIs). The purpose of this study was to present a large series of cases of this association. PATIENTS AND METHODS: The files of all patients with BRONJ associated with DIs who were treated in the department of oral and maxillofacial surgery from 2003 to 2009 were reviewed. Data on demographics, medical background, type, and duration of BP treatment before the development of BRONJ, mode of therapy, and therapeutic outcome were retrieved. RESULTS: Of the 27 patients enrolled into the study, 11 (41%) developed BRONJ while taking oral BPs and 16 (59%) developed BRONJ associated with intravenous BPs. BRONJ developed after mean periods of 68 months (median, 60), 16.4 months (median, 13), and 50.2 months (median, 35) in patients on alendronate, zoledronic acid, and pamidronate, respectively. Only 6 patients developed BRONJ during the first 6 months after DI placement. When BP treatment had been started before DI placement, there was a mean duration of 16.2 months (median, 11) until the appearance of BRONJ development. Long-term antibiotics and only essential surgical procedures comprised the treatment of choice, and the response rate was considerably better for patients taking the oral type of BPs. There was no significant association between BRONJ and diabetes, steroid intake, or smoking habits. CONCLUSION: Patients undergoing BP treatment and who receive DIs require a prolonged follow-up period to detect any development of BRONJ associated with DIs. 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Year of Publication 2010

Result 16.
Title Osteonecrosis of the jaw induced by oral administration of bisphosphonates in Asian population: five cases. Source Abstract Osteoporosis International. 21(3):527-33, 2010 Mar. SUMMARY: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) can occur irrespective of race. Old age and long-term use of corticosteroid

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may be a more reliable risk factor than racial characteristics. INTRODUCTION: BRONJ is an increasingly common problem. Most BRONJ occurs following an intravenous administration of bisphosphonate treatment for malignant bone disease and metastatic cancer. As the incidence of BRONJ caused by oral administration of bisphosphonate is quite low, it is believed that this medication is relatively safe and effective in preventing complications of osteoporosis, such as hip or spine fractures. The many known risk factors for BRONJ can be classified as drug-related, local, demographic, and systemic. One demographic and systemic risk factor is race. Most of the case reports of BRONJ present elderly, white women. METHODS: In this report, we describe five cases of BRONJ caused by oral administration of bisphosphonate in Asian population. RESULTS: All the patients were female and over 65 years old. Three patients had been prescribed with corticosteroids for rheumatoid arthritis. CONCLUSION: Irrespective of race, elderly women undergoing steroid therapy have an increased incidence of BRONJ even with oral administration of bisphosphonate. Year of Publication 2010

Result 17.
Title Bisphosphonates and time to osteonecrosis development. [Review] [102 refs] Source Abstract Oncologist. 14(11):1154-66, 2009 Nov. Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is a complication of long-term bisphosphonate (BP) use. Given the beneficial effects of BP on bone quality in patients with cancer or osteoporosis, it is of great importance to understand the risk as it relates to time to event or cumulative dose until the onset of disease. Because there is no information on the lowest toxic dose from clinical trials, here we report on a review of 71 case series published since 2003. We calculated the weighted mean time to event, as well as the minimum reported time and dose for zoledronate, pamidronate, and oral bisphosphonates. The mean time to BONJ after zoledronate treatment was calculated at 1.8 years

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and the minimum was 10 months; after pamidronate, the mean time was 2.8 years and the minimum was 1.5 years; and after oral BP therapy, the mean time was 4.6 years and the minimum was 3 years. Zoledronic acid seems to be the most potent among the nitrogen-containing BPs. Factors that seem to affect BONJ and time to event were invasive dental procedures and other comorbid factors such as advanced age, rheumatoid arthritis, diabetes, use of corticosteroids, vitamin D deficiency, and more. Understanding the pathophysiology of the disease requires further research. [References: 102] Year of Publication 2009

Result 18.
Title Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaws: clinical findings, assessment of risks, and preventive strategies. Source Abstract Journal of Oral & Maxillofacial Surgery. 67(5 Suppl):35-43, 2009 May. PURPOSE: Oral bisphosphonates are known to have potentially profound effects on oral health. A review of the evidence supporting answers to key clinical questions is necessary to assist surgeons in the care of their patients who are receiving oral bisphosphonates. MATERIALS AND METHODS: The literature is reviewed to address several questions, ie, what is the risk of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in my patient on oral bisphosphonates? Why are so few cases of BRONJ attributable to oral bisphosphonate use? What is the importance of cofactors in the development of osteonecrosis? How major a clinical problem is BRONJ, typically, in the oral bisphosphonate patient? What dental procedures are associated with a risk of BRONJ? Are other findings apart from BRONJ of importance in the oral bisphosphonate patient? Are there proven strategies to prevent BRONJ in the oral bisphosphonate patient? Should my patient discontinue the use of oral bisphosphonates temporarily or permanently? RESULTS: A review of the evidence offers information that will help in clinical decision-making. In general, the risk of BRONJ is between 1 in 10,000 and 1 in 100,000, but may increase to 1 in 300 after dental extraction. The great majority of BRONJ cases will likely remain in the intravenous population. Cofactors have not been firmly established, although smoking, steroid use, anemia, hypoxemia, diabetes, infection,

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and immune deficiency may be important. Rarely does BRONJ in the oral bisphosphonate patient appear to progress beyond stage 2, and many cases reverse with discontinuation of oral medication. Extraction is the only dental procedure shown to increase the risk of BRONJ. Dental implant therapy should be used with caution in the oral bisphosphonate patient. The benefits and risks of oral bisphosphonate use must be weighed individually and in consultation with the prescribing physician, before determining the need for temporary or permanent cessation of medication. CONCLUSION: Emerging evidence supports clinical decisions in favor of the oral and maxillofacial surgery patient taking oral bisphosphonates. Year of Publication 2009

Result 19.
Title Source Year of Publication 2009 Bisphosphonate related osteonecrosis of the jaws. Journal of Rheumatology. 36(2):450; author reply 453, 2009 Feb.

Result 20.
Title Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Source Abstract Oral Oncology. 44(9):857-69, 2008 Sep. A prospective study was performed in 80 patients receiving bisphosphonates in order to determine frequency of occurrence, risk factors, clinical presentation, radiology, pathology and proper treatment of osteonecrosis of the jaw (ONJ). Of 80 patients, 22 (28%) developed ONJ. There were 11 male and 11 female patients. Median age was 65 years. Ten patients (46%) had multiple myeloma (MM), 5 (23%) had breast cancer and 7 (32%) had other malignancies. Of 22 patients with ONJ, 14 patients (64%) received zoledronate, 3 (14%) received pamidronate, 4 (18%) received pamidronate later followed by zoledronate and 1 patient received ibandronate later followed by zoledronate. The median time of exposure in ONJ group was 32 months compared with 27 months in patients without ONJ. The mean induction time until bone exposure was 26 months for patients who received zoledronate, 54 months for pamidronate and 48 months for pamidronate followed by zoledronate.

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Thirteen patients (59%) had ONJ with bone exposure of mandible, 6 (27%) of maxilla and 3 (14%) of both jaws. ONJ occurred spontaneously in 5 patients (23%) and in 17 patients (77%) occurred after tooth extractions and surgical tooth removals (P<0.001). Nine patients (41%) had previous extractions of molars, 6 (27%) of premolars and 2 (9%) of front teeth. The cumulative hazard is significantly higher in zoledronate group (P=0.015). It was 3.48 times higher than the other group (pamidronate alone; pamidronate followed by zoledronate; ibandronate alone; etidronate alone; ibandronate followed by pamidronate; ibandronate followed by zoledronate; ibandronate followed by pamidronate and zoledronate). There was no association of ONJ with age, sex, use of high-dose or conventional chemotherapy or the use of corticosteroids, thalidomide or bortezomib (P>0.05). Patients diagnosed with multiple myeloma and breast cancer were found significantly associated with ONJ (P=0.001 and P=0.014, respectively). Long-term use of bisphosphonates (>2.5 years) increases the risk for development of ONJ. Intravenous application of zoledronate and previous dental extractions or surgical tooth removals are important risk factors of ONJ. Neither treatment with high-dose chemotherapy with autologous stem cell transplantation nor treatment with corticosteroids, thalidomide or bortezomib is a risk factor in this study. Year of Publication 2008

Result 21.
Title Influence of musculoskeletal conditions on oral health among older adults. [Review] [63 refs] Source Abstract American Journal of Public Health. 98(7):1177-83, 2008 Jul. Both musculoskeletal disorders and diseases of the oral cavity are common and potentially serious problems among older persons, yet little attention has been given to the links between them. Several musculoskeletal diseases, including osteoporosis, Paget's disease, and arthritic disorders, may directly involve the oral cavity and contiguous structures. Drugs used to treat musculoskeletal diseases, including corticosteroids and bisphosphonates, increase the risk of suppression of the immune system and osteonecrosis of the jaw, respectively. Many people with disabling osteoarthritis, rheumatoid arthritis, and other conditions have difficulty practicing good oral hygiene and traveling to dental offices for professional help. Various inexpensive measures can help such individuals, including education of their caregivers and

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provision of antimicrobial mouthwashes and special toothbrushes. [References: 63] Year of Publication 2008

Result 22.
Title Osteonecrosis of the jaw as an adverse bisphosphonate event: three cases of bone metastatic prostate cancer patients treated with zoledronic acid. Source Abstract Medicina Oral, Patologia Oral y Cirugia Bucal. 12(5):E351-6, 2007 Sep. Bisphosphonates offer a significant improvement in the quality of life for cancer patients; these potent inhibitors of bone resorption have been shown to markedly reduce the morbidity frequently resulting from bone metastases. Despite the success of bisphosphonates as therapeutic agents, however, toxicity in the form of osteonecrosis of the jaw (ONJ) is a rare complication whose incidence rate has climbed in recent years. ONJ is defined as an unexpected development of necrotic bone in the oral cavity, and is commonly associated with administration of the bisphosphonates Pamidronate and Zoledronate. Clinical features include local pain, soft-tissue swelling, and/or loose teeth; ONJ is also often correlated with previous dental procedures, such as tooth extractions, during biphosphonate therapy. Although additional risk factors-such as corticosteroids, chemotherapy, radiotherapy, trauma or infection-exhibit etiological associations with ONJ, the real pathobiology has not yet been fully elucidated. Here we report our findings on all 2005 OJN cases presented at our institution resulting from bone metastatic prostate cancer treated with zoledronic acid. The incidence of ONJ is nearly 3% (3 out of 104) in these patients. Year of Publication 2007

Result 23.
Title Bisphosphonate-associated osteonecrosis of the jaw: a review of 35 cases and an evaluation of its frequency in multiple myeloma patients. Source Abstract Leukemia & Lymphoma. 48(1):56-64, 2007 Jan. Over a period of 28 months, we observed five cases of osteonecrosis of the jaw (ONJ) in cancer patients treated with bisphosphonates (BP) at our institution. This prompted us to undertake a retrospective, multicenter

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study to analyse the characteristics of patients who exhibited ONJ and to define the frequency of ONJ in multiple myeloma (MM). We identified 35 cases in Gruppo Italiano Studio Linfomi centers during the period 2002 05. The median time from cancer diagnosis to the clinical onset of ONJ was 70 months. In these 35 cases of ONJ, 24 appeared 20 - 60 months after starting BP treatment. The time for the onset of ONJ was significantly shorter for patients treated with zoledronic acid alone than for those treated with pamidronate followed by zoledronic acid. The frequency of ONJ in the MM group during the study period was 1.9%, although the nature of the present study may have resulted in an underestimation of ONJ cases. Our analysis strongly suggested an association between the use of BP and the occurrence of ONJ, although we were unable to identify any definite risk factors with a retrospective study. The most frequently ONJ-associated clinical characteristics were chemotherapy treatment, steroid treatment, advanced age, female sex, anemia, parodonthopaties/dental procedures and thalidomide (in the case of MM patients). Year of Publication 2007

Result 24.
Title Source Abstract Bisphosphonates and jaw osteonecrosis: the UAMS experience. Otolaryngology - Head & Neck Surgery. 136(3):396-400, 2007 Mar. BACKGROUND: Over the past year at least 10 case series and several case reports on osteonecrosis of the jaw (ONJ) have been published with most found in the oral surgery literature. This clinical entity is largely unknown to head and neck surgeons. METHODS: Retrospective chart review. RESULTS: A total of 479 charts were reviewed, identifying 25 individuals meeting inclusion criteria. Mean age was 63.4 (standard deviation, 9.9) years; 40% were female. Multiple myeloma was the most common comorbidity. Twenty-five patients were treated with bisphosphonates for 4.4 years (range, 1 to 8 years); most commonly pamidronate before ONJ diagnosis. Forty-two percent (10) took steroids within the month before diagnosis. Fifty-two percent (11) underwent dental work before developing ONJ. CONCLUSION: These data reflect the importance of awareness of the

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possibility of ONJ with bisphosphonate therapy. Year of Publication 2007

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