Clinical Features and Management of Jaw Osteonecrosis in Patients Receiving Bisphosphonate Therapy.

Abstract Osteonecrosis of the jaws (ONJ) in patients receiving bisphosphonates is currently being discussed in the scientific literature. Oral bisphosphonates such as alendronate are commonly used to treat osteoporosis and have rarely been associated with ONJ in the benign setting. There is a greater number of reported ONJ cases in patients using intravenous bisphosphonates such as pamidronate and zoledronic acid for cancer-related indications. Many authors have associated local factors, such as dental extraction, periodontal disease, abscesses, and other oral problems, with the development of ONJ, and some have also suggested risk factors other than dental irritation. The aim of this study was to describe the clinical data from oncology patients with ONJ from a single institution. A total of 18 ONJ cases were identified among all patients treated at or referred to our institute (Hospital do Cancer A C Camargo, Sao Paulo, Brazil). These patients had a variety of primary malignancies: breast cancer (n = 7), multiple myeloma (n = 4), prostate cancer (n = 3), lung cancer (n = 3), and renal cancer (n = 1). Current bisphosphonate therapy included zoledronic acid (n = 15; 7 [47%] had received prior pamidronate therapy), pamidronate (n = 2), and alendronate (n = 1). The ONJ cases were managed conservatively using local irrigation with 0.12% chlorhexidine gluconate, debridement, and antibiotics. A total of 29 local ONJ lesions were found: 13 patients had 1 lesion, 3 patients had 2 lesions, and 2 patients had 5 lesions. The majority (n = 16 [89%]) of the patients experienced some level of local discomfort/pain, 6 complained of halitosis, and only 2 patients were asymptomatic. Clinically, 62% of the ONJ lesions were associated with dental work and extractions; only 20% occurred spontaneously. The majority (59%) of the ONJ lesions completely healed in 9 patients. Overall, most of the ONJ lesions were associated with dental procedures, and pain was the symptom most frequently reported. Excellent dental hygiene was found to be important for preventing infections and ONJ and also to contribute to lesion healing in the majority of the cases.

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Case of maxillary avascular necrosis due to oral bisphosphonates, presenting with signs of malignancy

The Journal of Laryngology & Otology ◽

10.1017/s0022215110000770 ◽

2010 ◽

Vol 124 (12) ◽

pp. 1318-1320 ◽

Cited By ~ 2

Author(s):

R Green ◽

K Blackmore ◽

A Robson

Keyword(s):

Case Report ◽

Avascular Necrosis ◽

World Literature ◽

Unusual Case ◽

Bisphosphonate Therapy ◽

Oral Bisphosphonates ◽

Dental Procedures ◽

History Of ◽

Intravenous Bisphosphonates ◽

Dental Work

AbstractObjective:We report a rare case of avascular necrosis of the maxilla secondary to oral bisphosphonates.Methods:Case report and review of the world literature concerning avascular necrosis as a result of bisphosphonate therapy.Case report:A 62-year-old woman presented with unilateral nasal obstruction, swelling of the cheek and an ulcerating lesion of the upper alveolus. She had a past medical history of osteoporosis, for which she took oral bisphosphonates. Investigation revealed necrosis of the maxilla, and avascular necrosis secondary to oral bisphosphonates was diagnosed.Conclusion:There have been several documented cases of avascular necrosis of the mandible and maxilla following intravenous bisphosphonates or dental procedures. In our case, bisphosphonates were only taken orally and no dental work had been undertaken. This patient's clinical presentation was highly suggestive of malignancy, and we would like to communicate this unusual case to other otolaryngologists.

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Bisphosphonate-induced osteonecrosis of the jaw: Incidence and risk factors in patients with breast cancer and gynecological malignancies

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1113 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1113-1113

Author(s):

V. Beck ◽

E. Solomayer ◽

M. Krimmel ◽

C. Reinert ◽

T. Fehm

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Zoledronic Acid ◽

Bone Metastases ◽

Osteonecrosis Of The Jaw ◽

Bisphosphonate Therapy ◽

Gynecological Malignancies ◽

Dental Procedures ◽

The Mean ◽

Number Of Treatment

1113 Background: Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. They are successfully used in conditions of increased bone turnover such as osteoporosis or bone metastases. Since 2003 multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. Our purpose was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies. Patients and Methods: ONJ was assessed retrospectively for all patients with breast cancer or gynecological malignancies treated with bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April 1999 until May 2006. Results: 10 of 310 (3%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. All patients with ONJ were treated for bone metastases. Except one all patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. In 4 of 10 patients this was the only bisphosphonate given. The remaining 6 patients had received at least one of the other bisphosphonates (alendronate, ibandronate, clodronate or pamidronate) before or after zoledronic acid therapy during their course of disease. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p<0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27 ±18 cycles (median: 21 cycles, range 6–62 cycles) and the mean duration of bisphosphonate therapy was 29 ±20 months (median: 22 months, range 1–67 months). In contrast, the mean number of treatment cycles in patients without manifestation of ONJ was 11 ±12 cycles (median: 6 cycles, range 1–90 cycles). The mean duration of therapy was 12 months (median: 7 months, range 1–81 months). Conclusion: Osteonecrosis of the jaw is regarded a major side effect of bisphosphonate therapy. Length of exposure to bisphosphonates and the number of treatment cycles seem to be the most important risk factors for the development of ONJ. In addition, recent dental procedures favours the development of an ONJ. No significant financial relationships to disclose.

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Osteonecrosis of the jaw associated with intravenous bisphosphonate therapy—A single institution experience

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.18553 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 18553-18553 ◽

Cited By ~ 2

Author(s):

E. M. Wallace ◽

K. I. Quintyne ◽

B. M. Cantwell ◽

P. M. Calvert ◽

G. D. Leonard

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Zoledronic Acid ◽

Metastatic Breast ◽

Median Number ◽

Osteonecrosis Of The Jaw ◽

Bisphosphonate Therapy ◽

Unknown Primary ◽

Dental Procedures ◽

Increased Risk

18553 Background: Osteonecrosis of the jaw (ONJ) is a debilitating disease that has been associated with cancer therapy. Recently a link between ONJ and chronic intravenous (IV) bisphosphonates has been suggested. We assessed the incidence of ONJ and its risk factors in patients treated with IV bishosphonates at our institution. Methods: All patients with a cancer diagnosis treated at our institution with at least four cycles of either IV Zoledronic Acid, Pamidronate, or a combination of both, from 2000–2005 were evaluated using outpatient records. Patients with ONJ were identified and their characteristics were compared to all patients receiving bisphosphonate therapy. Results: One hundred and twenty-one patients were evaluated, 36 Male and 85 Female. Median age- 62 (Range 34–85). Seventy-six had metastatic Breast cancer, 25 Prostate, 7 Lung, 3 Colorectal, 3 Renal, 2 unknown primary, 1 each of Penile, Bladder, Seminoma, Lymphoma and Melanoma. Forty patients received Pamidronate infusions alone, 51 Zoledronic Acid alone and 30 a combination of the two. The median number of Pamidronate infusions was 8 (Range 4–10), Zoledronic infusions 10.7 (Range 4–32), and a combination of pamidronate and zoledronic acid was 12 (Range 5–66). Three patients developed ONJ. All 3 patients were female, had a median age of 62 (range 52–74) and had metastatic breast cancer. The median number of bisphosphonate infusions prior to the development of ONJ was 35 (Range 18–47). All patients had chest wall radiotherapy and 1 had chemotherapy and steroids. No patients had dental procedures or prolonged antibacterial therapy. Conclusions: ONJ is a complication associated with IV Bisphosphonate therapy. Our study suggests that female sex, zoledronic acid, and prolonged administration of bisphosphonates, may confer an increased risk for the development of ONJ. Further prospective studies with adequate power are needed to clarify what patients are most at risk for developing ONJ and what measures are needed to prevent its occurrence. No significant financial relationships to disclose.

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Osteonecrosis of the Jaws Secondary to Bisphosphonate Therapy: A Case Series

The Journal of Contemporary Dental Practice ◽

10.5005/jcdp-9-1-63 ◽

2008 ◽

Vol 9 (1) ◽

pp. 63-69 ◽

Cited By ~ 11

Author(s):

Satish K. S. Kumar ◽

Michael C. Meru ◽

Parish P. Sedghizadeh

Keyword(s):

Maxillofacial Surgery ◽

Case Series ◽

Poor Quality ◽

Bisphosphonate Therapy ◽

Oral And Maxillofacial Surgery ◽

Osteonecrosis Of The Jaws ◽

Cancer Metastases ◽

Dental Procedures ◽

Southern California School ◽

School Of Dentistry

Abstract Aim The objective of this report is to present the clinical experiences of several patients affected with osteonecrosis (ONJ) secondary to bisphosphonate (BP) therapy and to provide a discussion of the specific BPs implicated in this condition. Background ONJ secondary to BP therapy is becoming an increasingly reported complication following dental therapy. This is particularly true of surgical dental procedures such as extractions. BPs are a class of pharmaceuticals used in the treatment of numerous disorders affecting bone, including osteoporosis, cancer metastases to bone, hypercalcemia of malignancy, and multiple myeloma. Although ONJ is a more recently described phenomenon, it is an emerging problem that may be associated with significant morbidity such as oral dysfunction, impaired eating ability, pain, and compromised esthetics resulting in a poor quality of life in affected patients. Case Report This is a description of 13 patients affected with ONJ secondary to BP therapy managed at the Orofacial Pain & Oral Medicine Center, Special Patients Clinic, and Oral and Maxillofacial Surgery Clinic at the University of Southern California, School of Dentistry between October 2005 and April 2007, with a discussion of the specific BPs implicated in this condition, the clinical presentation, management, and follow-up. Summary Thorough reporting of every case of ONJ is important to help advance the understanding of this poorly understood condition. The authors’ approach to care represents a more conservative mode to management than previously described by many investigators. Citation Kumar SKS, Meru MC, Sedghizadeh PP. Osteonecrosis of the Jaws Secondary to Bisphosphonate Therapy: A Case Series. J Contemp Dent Pract 2008 January;(9)1:063-069.

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Bisphosphonates and Osteonecrosis of the Jaws: Incidence in a Homogeneous Series of Patients with Newly Diagnosed Multiple Myeloma Treated with Zoledronic Acid.

Blood ◽

10.1182/blood.v106.11.3461.3461 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3461-3461 ◽

Cited By ~ 15

Author(s):

Patrizia Tosi ◽

Elena Zamagni ◽

Delia Cangini ◽

Paola Tacchetti ◽

Massimo Offidani ◽

...

Keyword(s):

Multiple Myeloma ◽

Zoledronic Acid ◽

Rare Complication ◽

Maxillofacial Surgery ◽

Treatment Protocol ◽

Purulent Discharge ◽

Newly Diagnosed ◽

Osteonecrosis Of The Jaws ◽

Dental Procedures ◽

Bone Biopsies

Abstract Osteonecrosis of the jaws (ONJ) is a rare complication that has been described as osteoradionecrosis in patients who had previously undergone radiotherapy for head and neck cancer or similar disorders. It has been recently reported that the incidence of ONJ has significantly increased since the wide application of bisphosphonates as specific therapy of cancer related bone disease. No consensus on diagnostic criteria does presently exist, the pathogenesis of this complication is unknown and the relative contribution of repeated trauma from dental procedures, poor oral hygiene, concomitant chemotherapy, and cancer bone involvement has not been clarified yet. All the same, no data have so far been presented concerning the incidence of ONJ in a homogeneous series of patients with respect to disease status and treatment received. For this purpose, we have retrospectively evaluated the occurrence of ONJ in patients with symptomatic newly diagnosed multiple myeloma enrolled in the “Bologna 2002” clinical trial. According to treatment protocol, all patients received four months of combined thalidomide (100mg/d for two weeks and 200mg/d thereafter) and dexamethasone (40mg/d on d 1–4, 9–12, 17–20/28d on odd cycles and on d 1–4 on even cycles) followed by cyclophosphamide 7g/m2 + G-CSF and PBSC collection, and two courses of Melphalan 200mg/mq and PBSC transplantation. Zoledronic acid was administered at 4mg/28 d throughout the whole study period and afterwards until disease progression. Out of 225 patients analyzed so far (median follow-up = 26 months), ONJ was diagnosed in 6 cases (2.7%), median time from start of treatment and occurrence of dental symptoms was 23 months (range 13–32 months). All the patients underwent dental extraction and/or oral/maxillofacial surgery that resulted in areas of non-healing bone with persistent purulent discharge. Bone biopsies confirmed bone necrosis and inflammation; in 1 case, however, a concomitant infiltration of monoclonal plasma cells was detected in the site of necrosis. In conclusion, results of this retrospective analysis indicate that the occurrence of ONJ among newly diagnosed MM patients receiving long-term (median: 2 years) zoledronic acid treatment was approximately 3%. Surgery can significantly impact patients outcome, so that, according to currently available recommendations on ONJ, dental procedures should be avoided. In addition, the role played by disease itself in the pathogenesis of this complication should not be overlooked.

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Chemical Features of Bisphosphonates and Histopathological Outcomes in Rat Jaw Treated with Zoledronic Acid Combined with Dexamethasone

Revista de Chimie ◽

10.37358/rc.18.7.6420 ◽

2018 ◽

Vol 69 (7) ◽

pp. 1802-1807

Author(s):

Ioana Aurita Albu Stan ◽

Cecilia Petrovan ◽

Diana Cerghizan ◽

Daniel Emil Albu ◽

Adriana Elena Craciun ◽

...

Keyword(s):

Multiple Myeloma ◽

Zoledronic Acid ◽

Bone Resorption ◽

Bisphosphonate Therapy ◽

Inorganic Pyrophosphate ◽

Osteonecrosis Of The Jaws ◽

The Past ◽

Concurrent Use ◽

Exposed Bone ◽

First Time

Bisphosphonate related osteonecrosis of the jaws (BRONJ) is a pathological entity described for the first time in 2003; three criteria are mandatory: no radiotion therapy,exposed bone in oral cavities for at least eight weeks with no signs of healing, bisphosphonate therapy in present or in the past,in patients with bisphosphonate therapy in present or in the past. Bisphosphonates (BPs) are stable analogues of natural inorganic pyrophosphate, which inhibit bone resorption. In literature, most patients diagnosed with BRONJ were suffering from multiple myeloma and they had a treatment with nitrogen containing BPs and steroids such as dexamethasone intravenously. With this study we have aimed to achieve a rat model of BRONJ and to evaluate histopathological findings how concurrent use of BPs and steroids can affect emergence of BRONJ in this study.

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A Clinical and Histological Study about the Socket Preservation in a Patient under Oral Bisphosphonates Treatment: A Case Report

Biology ◽

10.3390/biology10040262 ◽

2021 ◽

Vol 10 (4) ◽

pp. 262

Author(s):

Antonello Falco ◽

Francesco Bataccia ◽

Lorenzo Vittorini Orgeas ◽

Federico Perfetti ◽

Mariangela Basile ◽

...

Keyword(s):

Case Report ◽

Histological Study ◽

Healing Process ◽

Signs And Symptoms ◽

Bisphosphonate Therapy ◽

Graft Material ◽

Oral Bisphosphonates ◽

Socket Preservation ◽

Oral Bisphosphonate ◽

Histological Data

The aim of the present study is to assess the clinical and histological healing of a post-extractive alveolus following the procedure for socket preservation, in a patient receiving oral bisphosphonates for more than 6 years. After the extraction, enzymatically-deantigenated horse bone granules and an equine pericardium membrane were used to preserve the tooth socket. The patient was placed on a monthly follow-up in order to monitor the healing process. A 3 mm trephine bur was used to drill the bone for implant site preparation and to collect the bone sample. No signs and symptoms related to osteonecrosis of the jaws were reported. Histological data showed that, after 5 months, the mean percentages of trabecular bone, bone marrow and residual bone graft were respectively 45.74 ± 0.09%, 48.09 ± 0.08%, and 6.16 ± 0.01%. The residual graft material appeared to be osteointegrated and none of the particles appeared to be encapsulated. The present case report supports the guidelines that assume that patients undergoing oral bisphosphonate therapy can be eligible for surgical therapy. More clinical studies with larger sample sizes are needed to support this clinical evidence.

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