Zoledronate and osteonecrosis of the jaw in osteoporosis: incidence and risk factors. Analysis of the French Pharmacovigilance Database.

INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) have been characterized with the use of oral bisphosphonates in osteoporosis and zoledronate in oncology. Uncertainties remain, though, with the occurrence of BRONJ related to the use of zoledronate in osteoporosis. OBJECTIVES: We aimed to estimate the incidence and characterize the risk factors of zoledronate-associated BRONJ in osteoporosis as compared with oral bisphosphonates in real life setting. METHODS: Cases of BRONJ associated with zoledronate, alendronate or risedronate were extracted from the French pharmacovigilance database up to 2020. The incidence of BRONJ was estimated as their respective numbers related to cases of BRONJ in patients treated with bisphosphonates for osteoporosis, over the same period, according to the Medic'AM database. RESULTS: Between 2011 and 2020, BRONJ incidence with zoledronate was 9.6/100,000 patient-year (PY), significantly higher than with alendronate (5.1/100,000 PY, P<0.001), and risedronate (2.0/100,000 PY, P<0.001). The number of patients treated with bisphosphonates has steadily decreased by 44.5% over 10 years. Meanwhile, the incidence of BRONJ decreased (5.8/100,000 PY in 2011; 1.5/100,000 in 2020), although a rebound was observed in 2018, including 47.6% of BRONJ following denosumab. Apart from classical risk factors, recent dental cares stood out in more than 40% of BRONJ, and zoledronate had a shorter exposure time than oral bisphosphonates. CONCLUSIONS: In a real-life setting, our data confirm that zoledronate-associated BRONJ in osteoporosis is scarce, seeming slightly more common compared with oral bisphosphonates. We also raise awareness of dental care guidelines and greater vigilance when using bisphosphonates in patients with previous exposure to denosumab.

Preserving bone in cancers of the elderly: A necessity.

The occurrence of bone fractures is frequent in the elderly population, and in cancer patients, especially with bone metastases. The growing incidence of cancer associated with an aging population implies important health challenges, including bone health. Decisions on cancer care in older adults have to take into account older adults' specificities. Screening tools as G8 or VES 13 and evaluating tools as comprehensive geriatric assessment (CGA) do not include bone-related items. Bone risk assessment is indicated according to identification of geriatric syndromes such as falls, history, and the oncology treatment plan. Some cancer treatments disrupt bone turnover and decrease bone mineral density. This is mainly caused by hypogonadism, induced by hormonal treatments and some chemotherapies. Treatments can also cause direct (i.e., chemotherapy, radiotherapy or glucocorticoids) or indirect toxicity through electrolyte disorders (i.e., some chemotherapies or tyrosine kinase inhibitors) on bone turnover. Bone risk prevention is multidisciplinary. Certain interventions proposed in the CGA aim to improve bone health and reduce the risk of falling. It is also based on the drug management of osteoporosis, and the prevention of complications from bone metastases. Management of fractures, related or not to bone metastases relates to the concept of orthogeriatrics. It is also based on the benefit-risk ratio of the operation, access to minimally invasive techniques, prehabilitation or rehabilitation, but also the prognosis related to cancer and geriatric syndromes. Bone health is essential in older cancer patient's care. Bone risk assessment should be part of CGA in routine use and specific decision-making tools should be developed. Bone event management must be integrated throughout the patient's care pathway and oncogeriatrics multidisciplinarity should include rheumatological expertise.

Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS).

BACKGROUND: Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone. METHODS: This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis. DISCUSSION: The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts. TRIALS REGISTRATION: ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study.

Does bevacizumab increase joint pain in patients with cancer? Results of the prospective observational BEVARTHRALGIA study.

PURPOSE: The occurrence of arthralgia and myalgia during treatment with bevacizumab (Bev) has been described but not spontaneously reported. We aimed to evaluate the frequency of arthralgia in patients treated with Bev and identify the risk factors. METHODS: In this observational prospective study, a self-administered questionnaire was distributed to patients at the initiation of Bev and at 3 and 6 months of treatment. Bev (5-15 mg/kg) was administered every 2 or 3 weeks, with or without chemotherapy. RESULTS: A total of 71 patients (42 with colorectal cancer, 22 with ovarian cancer, and 7 with lung cancer) were enrolled from January to November 2018. All patients completed the questionnaire at initiation, while only 56 (78.9%) and 36 (50.7%) patients completed the questionnaire at 3 and 6 months, respectively. The frequency of joint pain was 29.6% before Bev treatment and increased to 41.8% and 50% at 3 and 6 months, respectively, without reaching significance. The evolution of pain was significant according to the Common Terminology Criteria for Adverse Events grades (P = 0.032). No significant increase in the impact of pain on instrumental or elementary activities was observed over time. The frequency of arthralgia significantly increased at 3 months in patients with ovarian cancer versus those with colorectal cancer (odds ratio: 19.50; 95% confidence interval 4.53-83.98; P < 0.001). CONCLUSIONS: Bev­including regimens tend to be associated with a significant increase in the frequency of arthralgia in women treated for ovarian cancer. Physicians should be aware of this side effect. CLINICAL TRIAL NUMBER: NCT03455907, date of registration: March 7, 2018.

Adapting palliative radiation therapy for bone metastases during the Covid-19 pandemic: GEMO position paper.

The current health crisis caused by COVID-19 is a challenge for oncology treatment, especially when it comes to radiotherapy. Cancer patients are already known to be very fragile and COVID-19 brings about the risk of severe respiratory complications. In order to treat patients safely while protecting medical teams, the entire health care system must optimize the way it approaches prevention and treatment at a time when social distancing is key to stemming this pandemic. All indications and treatment modalities must be re-discussed. This is particularly the case for radiotherapy of bone metastases for which it is possible to reduce the number of sessions, the frequency of transport and the complexity of treatments. These changes will have to be discussed according to the organization of each radiotherapy department and the health situation, while medical teams must remain vigilant about the risks of complications of bone metastases, particularly spinal metastases. In this short piece, the members of the GEMO (the European Study Group of Bone Metastases) offer a number of recommendations to achieve the above objectives, both in general and in relation to five of the most common situations on radiation therapy for bone metastases.

Bone Metastasis: Current State of Play.

Bone metastasis (BM) in cancer remains a critical issue because of its associated clinical and biological complications. Moreover, BM can alter the quality of life and survival rate of cancer patients. Growing evidence suggests that bones are a fertile ground for the development of metastasis through a "vicious circle" of bone resorption/formation and tumor growth. This review aims to outline the current major issues in the diagnosis and management of BM in the most common types of osteotropic cancers and describe the mechanisms and effects of BM. First, we discuss the incidence of BM through the following questions: Are we witnessing an increase in incidence, and are we now better equipped with modern imaging techniques? Is the advent of efficient bone resorption inhibitors affecting the bigger picture of BM management? Second, we discuss the potential effects of cancer progression and well-prescribed drugs, such as multitarget tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, and immune checkpoint inhibitors, on BM. Finally, we examine the duality of the effects of some therapies that may help in cancer treatment but may also contribute to further BM.

French recommendations on strategies for preventing and treating osteoporosis induced by adjuvant breast cancer therapies.

Standard adjuvant therapies for breast cancer such as chemotherapy or aromatase inhibitor and LH-RH agonist hormone therapy are associated with significant survival gains but also induce bone loss by aggravating the estrogen deprivation. The bone loss may be substantial, notably during early treatment, and occurs regardless of the baseline bone mineral density values. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on literature review, about osteoporosis prevention and treatment in these patients. The following scientific societies contributed to the work: Société Française de Rhumatologie (SFR), Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO), Groupe Européen d'Etudes des Métastases Osseuses (GEMO), Association Francophone pour les Soins Oncologiques de Support (AFSOS), Société Française de Sénologie et de Pathologie Mammaire (SFSPM), Société Française de Radiothérapie Oncologique (SFRO). Drug prescription and reimbursement modalities in France were taken into account. These recommendations apply to postmenopausal women taking systemic chemotherapy and/or aromatase inhibitor therapy, non-postmenopausal women taking LH-RH agonist therapy, and non-postmenopausal women with persistent amenorrhea 1 year after chemotherapy completion. All women in these three categories should undergo an evaluation of bone health and receive interventions to combat risk factors for bone loss. Patients with a history of severe osteoporotic fracture and/or a T-score value <-2.5 should receive osteoporosis drug therapy. The FRAX® score should be used to guide treatment decisions in patients whose T-score is between -1 and -2.5. General osteoporosis prevention measures should be applied in patients without criteria for osteoporosis drug therapy, who should undergo bone mineral density measurements 18-24 months later if the baseline T-score is<-1 and 3-5 years later if the baseline T-score is>-1. The anti-tumor effect of bisphosphonates and denosumab was not considered when establishing these recommendations.

French recommendations for osteoporosis prevention and treatment in patients with prostate cancer treated by androgen deprivation.

Androgen-deprivation therapy (ADT) in patients with prostate cancer can be achieved surgically or chemically, notably by prescribing LHRH analogs. Major bone loss occurs rapidly in both cases, due to the decrease in testosterone levels, and can increase the fracture risk. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on a literature review, about osteoporosis prevention and treatment in patients on ADT. The following scientific societies contributed to the work: Société française de rhumatologie (SFR), Groupe de recherche et d'information sur les ostéoporoses (GRIO), Groupe européen d'études des métastases osseuses (GEMO), Association francophone pour les soins de support (AFSOS), Association française d'urologie (AFU), Société française de radiothérapie oncologique (SFRO). Medication prescription and reimbursement modalities in France were taken into account. The recommendations state that a fracture-risk evaluation and interventions targeting risk factors for fractures should be provided to all patients on ADT. Those patients with a history of severe osteoporotic fracture and/or a T-score < -2.5 should receive osteoporosis therapy. Patients whose T-score is between -1.5 and -2.5 should be treated if they exhibit at least two other risk factors among the following: age ≥ 75 years, history of non-severe fracture after 50 years of age, body mass index < 19 kg/m2, at least three comorbidities (e.g., cardiovascular disease, depression, Parkinson's disease, and dementia), current glucocorticoid therapy, and repeated falls. When the decision is difficult, FRAX® score determination and an assessment by a bone disease specialist may be helpful. When osteoporosis therapy is not indicated, general measures should be applied, and bone mineral density measured again after 12-24 months. The anti-tumor effects of bisphosphonates and denosumab fall outside the scope of these recommendations.

Evaluation of the Relevance of Surgery in Patients with Multiple Myeloma Harboring Symptomatic Spinal Involvement: A Retrospective Case Series.

BACKGROUND: Multiple myeloma spinal involvement can lead to bone fractures and neurologic impairment that can severely alter quality of life. The role of surgery is controversial, given its high morbidity, and the lack of evidence. We hereby aim to evaluate efficacy and safety of surgery in the management of symptomatic spinal lesions in patients with multiple myeloma. METHODS: We included all patients operated on for a myeloma-related spinal lesion in our institution between 2007 and 2015. Demographic, clinical, and surgical data were collected as well as hematologic profiles. We retrospectively assessed the surgical success of the procedures, if at 3 months the patient fulfilled the following 4 criteria: pain relief, ability to walk, spinal stability, and no relevant morbidity. RESULTS: Thirty-six men and 19 women, with a median age of 62 years, were included. Seventeen patients underwent an emergency intervention, whereas 38 patients underwent elective surgery. At 3 months, 88.2% and 96.1%, respectively, of patients experienced pain relief and were able to walk. Spinal stability was considered satisfactory for 94.1% of patients. We reported 8 major complications in 8 patients. Altogether, 34 patients (61.8%) fulfilled all criteria for surgical success. An International Staging System score of 1 and the absence of previous chemotherapy were significantly associated with surgical success. CONCLUSIONS: Management of myeloma-related spine lesions requires a multidisciplinary approach. Surgery rapidly provides both decompression and stabilization. Using a strict patient-specific evaluation, we reported rewarding functional results, with acceptable morbidity. Surgery for multiple myeloma vertebral lesions seems to be a valuable option for carefully selected patients.

Decision Making for the Surgical Treatment of Vertebral Metastases Among Patients with Short Predicted Survival.

BACKGROUND: A wide spectrum of treatment choices is proposed for poor-prognosis patients with vertebral metastases. The continuous increase of this population and the propagation of less invasive techniques necessitate further study concerning which patients could benefit from palliative surgery. METHODS: All patients with a Tokuhashi score ≤8 who had undergone palliative surgical treatment for vertebral metastasis within 4 years were retrospectively reviewed. Demographics, clinical characteristics, and data concerning the disease and the operation were recorded. Patients were assessed on discharge and at 2 months concerning eventual benefit from surgery, based on pain measurements, motor function (Frankel grade), spinal stability assessment, and complications. Statistical analysis was performed to detect possible interrelations. RESULTS: Eighty-eight patients were reviewed. The average age was 56.5 years. The mean Tokuhashi score was 5.9, and the mean Karnofsky score was 56.4. Thirty-six patients experienced immediate improvement, 12 were lost to follow-up, and 42 were found to have benefited from surgery 2 months later. High Karnofsky score, radicular pain, morphine use, absence of complications, and immediate improvement predicted benefit from surgery. CONCLUSIONS: Decision making for a patient with poor prognosis concerning eventual surgery for a vertebral metastasis should be based mainly on the patient's clinical presentation; the primary cancer site is of less importance.

Evaluation of the relevance of surgery in a retrospective case series of patients who underwent the surgical treatment of a symptomatic spine metastasis from lung cancer.

BACKGROUND: The management of spine metastases is an increasing concern for spine surgeons. When considering surgery, it is crucial to ensure that its iatrogenic effects will not exceed its potential benefits, particularly in frail patients with short life expectancy. Among all prognostic factors, the primary site of cancer is the most important, lung cancer being the poorest. Although surgery has shown its effectiveness in the management of spine metastases, there is a lack of studies focusing on lung cancer alone. PURPOSE: To assess the effectiveness and safety of surgery in the management of symptomatic spine metastases from lung cancer. METHODS: We retrospectively reviewed all patients (n = 53) who underwent surgery for spine metastasis from lung cancer at the Lille University Hospital between January 2005 and December 2011. Patients for whom surgery was effective to restore or preserve ambulation, to relieve pain, and to ensure stability without severe complication were considered "surgical success". RESULTS: No patient was lost to follow-up and vital status data were available for all patients. The median survival was 2.1 months and was not influenced by the surgical success (p = 0.1766). We reported seven major complications in seven patients, including three epidural haematoma, two massive pulmonary embolisms and two deaths from cardiopulmonary failure. The surgical success rate was 49 % and on univariate analysis, the factors that have influenced the postoperative outcome were the KPS (p < 0.001), the Frankel grade (p = 0.0217) and the delay between the cancer diagnosis and the occurrence of spine metastases (p = 0.0216). CONCLUSION: A strict patient selection is required to limit the iatrogenic effect of surgery, which may alter the quality of life of these frail patients with limited life expectancy.

Spine metastases: are minimally invasive surgical techniques living up to the hype?

Surgery is still considered the mainstay treatment of spine metastases. However, conventional surgery is associated with a high complication rate that may delay the initiation of adjuvant therapies and make some patients not eligible. Minimally invasive surgical techniques have been developed to overcome these drawbacks while providing the same benefits than standard open surgery. In recent years, there has been a flourishing enthusiasm demonstrating the advantages of these various techniques. Although, it is clear that these techniques have greatly improved the treatment of spine metastases, each has its own limitations. In this report, we list the main minimally invasive surgical techniques emphasizing their advantages and drawbacks.

Management of neoplastic spinal tumors in a spine surgery care unit.

BACKGROUND CONTEXT: Spinal cord compression and fracture are possible complications of spine metastasis and multiple myeloma. Prompt diagnosis and treatment of threatening lesions are likely to reduce the frequency of these dreaded complications. PURPOSE: To evaluate the proportion of neoplastic spine lesions operated on emergency. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: All patients who underwent palliative surgery for the treatment of a neoplastic spine lesion in our institution between 2005 and 2012. OUTCOME MEASURES: Percentage of patients who underwent surgery as an emergency for acute fracture or rapid neurological decline. METHODS: We retrospectively reviewed the data of all patients who underwent palliative surgery for the treatment of a neoplastic spine lesion from solid cancer or multiple myeloma, in our institution between January 2005 and December 2012. The study was supported by grant from our institution. RESULTS: A total of 317 patients were included in the study. There were 166 men and 151 women and the mean age was 57.97 years (range 26-88; SD 12.45). The cancer was known for 224 patients, while the lesion revealed the disease for the other 93 patients. The percentage of patients with known cancer operated as an emergency in our institution decreased significantly between 2005 and 2012 (p = 0.0006). CONCLUSION: Due to the variability of clinical and radiological presentations, best care requires a truly multidisciplinary approach, to offer each patient a prompt and individualized treatment option, which is likely to reduce the incidence of emergency surgeries.

Ruminococcus gnavus: an unusual pathogen in septic arthritis.

Ruminococcus gnavus is an anaerobic Gram positive coccus that can be found in the gastrointestinal tract of animals and humans. We report a case of septic arthritis caused by R. gnavus that was identified by mass spectrometry and confirmed by 16S rRNA sequencing.

[Multidisciplinary meetings dedicated to bone metastases: a historical perspective and rationale]. / Réunions de concertation pluridisciplinaire (RCP) dédiées aux métastases osseuses : historique et justification.

Bone metastases of solid tumors have a strong impact on patient's autonomy and vital outcome. Drugs specifically targeting bone remodeling as well as local treatment (radiotherapy, osteoplasty, surgery) make the management of bone metastasis a multidisciplinary process. Multidisciplinary teams (MDTs) dedicated to bone metastasis aim at providing the diagnosis of certainty, defining treatment indications and monitoring follow-up. The MDTs are the place for innovation in imaging and treatments of bone metastases.

Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma.

OBJECTIVES: To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. METHODS: Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. RESULTS: Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. CONCLUSIONS: Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. KEY POINTS: • Low-dose biplanar skeletal surveys can readily assess bone lesions in multiple myeloma. • In marked radiographic osteopenia and obesity, LDB SS diagnostic performance is reduced. • Low-dose biplanar skeletal surveys cannot yet replace digital SS in all MM patients.

Molecular interactions between zoledronic acid and bone: An in vitro Raman microspectroscopic study.

The aim of this study was to investigate molecular interactions between a bisphosphonate (BP), zoledronic acid, and bone tissue by the use of Raman microspectroscopy. In this way, samples of hydroxyapatite (HA), as a bone model, and Wistar rat femurs were soaking in zoledronic acid solutions. Sample surfaces were studied by Environmental Scanning Electron Microscopy and Raman spectroscopy. The amount of zoledronic acid incorporated onto the samples and the inorganic phosphate released in solution were determined by (31)P NMR spectroscopy. Total carbonate content in solution was evaluated by inorganic carbon analyser. After impregnation new Raman bands with frequencies close to characteristic peaks of zoledronic acid (in particular phosphate moieties and imidazole ring of the R2 side-chain) were observed on both types of samples. Physico-chemical parameters of the bone were also significantly modified (P<0.0001). The mineral to organic ratio and the carbonate to phosphate ratio decreased and the crystallinity increased. Released inorganic phosphate and carbonate were detected in the solutions. The Raman shift of the bands corresponding to the phosphate groups and the imidazole ring of the BP highlight their implication in the binding to the mineral. The detection of released inorganic phosphate and carbonate in solution, the modifications of the mineral to phosphate ratio and the carbonate to phosphate ratio reveal that BP decrease the amount of inorganic phosphate and limit the dissolution of bone mineral. The increase of the crystallinity after BP binding shows a re-organisation of the lattice with a higher symmetry. Thus, it seems that zoledronic acid has an important contribution on the increase of crystallinity. The use of Raman spectrometry brings new and complementary information on the impact of zoledronic acid on bone composition at molecular level. Raman spectrometry could help to understand by which way BPs improve bone strength and decrease fracture risk.

Development of a score that predicts survival among patients with bone metastasis revealing solid tumor.

BACKGROUND: Bone metastases revealing solid tumors require a multidisciplinary treatment that may include aggressive surgery. Nevertheless, decision making is very difficult because of lack of reliable guidance for life expectancy. Therefore, we had conducted a retrospective study to analyze prognostic factors in this vulnerable population. MATERIALS AND METHODS: We reviewed the medical charts of 119 consecutive patients with solid tumors treated between August 1999 and December 2007. Survival was estimated using Kaplan-Meier method. Prognostic factors were assessed with Log-rank test and Cox model. There were 77 men and 42 women. RESULTS AND DISCUSSION: The median age was 57 (range, 29-84). The most frequent primaries were lung (51 cases), unknown primary (42 cases), and breast (six cases). The median overall survival was 118 days (1-2,815). Six independent prognostic factors were identified by multivariate analysis: Karnosky index < 80% (HR = 1.92), albuminemia < 38 g/l (HR = 2.60), natremia < 135 mEq/l (HR = 2.78), platelet count > 500,000/mm(3) (HR = 2.71), cutaneous metastasis (HR = 4.6), and pleural metastasis (HR = 4.76). For example, patients with < or =2 of these prognostic factors experienced a median overall survival of 196 days (1-2,875) and their risk of death within the 90 days was 15/77. On the contrary, the patients with more than two poor prognostic factors experienced a median overall survival of about 80 days (1-834) and their risk of early death was 22/32. We had proposed an easily obtained at bedside score that needs further validation on independent cohort.

[Osteonecrosis of the jaw and bisphophonates in oncology]. / Ostéonécrose des maxillaires et bisphosphonates en cancérologie.

Bisphosphonates are potent osteoclastic inhibitors that are indicated in the prevention of bone complications. They could also be of interest in the prevention of bone metastases. Several recent international publications have highlighted the onset of osteonecrosis of the jaw (ONJ) in patients treated with bisphosphonates. These osteonecroses manifest in the form of bone exposure, recent tooth mobility, swelling and inflammation and, occasionally, localised pain but they can remain asymptomatic for weeks or even months. The prevalence of these osteonecroses in cancer patients treated with bisphosphonates could range from 1 to 10%. In most cases (60 to 80%), ONJ develops after alveolo-dental surgery (e.g. tooth extraction). Length of exposure to bisphosphonate probably increases the risk. Our recommendations regarding the diagnosis, classification, prevention and treatment of cases of ONJ observed during bisphosphonate administration are based on published studies and our experience. It is obvious that the use of bisphosphonates is undoubtedly beneficial in the treatment of bone complications but the incidence of ONJ during long-term treatments and at high doses warrants preventive measures. These measures are straightforward : bucco-dental repair prior to treatment, good hygiene and regular monitoring during treatment. Current, non-invasive procedures are still permitted. In other cases, the suspension of treatment is indicated until healing is complete. The increase in the incidence of ONJs, serious adverse events, raises the issue regarding duration and administration of bisphosphonate treatment in the management of bone metastases. Studies are currently underway in an attempt to answer this issue.

Thirteen cases of jaw osteonecrosis in patients on bisphosphonate therapy.

INTRODUCTION: We report on our experience with 13 cases of jaw osteonecrosis in patients treated with amino-bisphosphonates. METHOD: Data were collected by a regional observatory for jaw osteonecrosis in northern France via letters sent to all physicians likely to manage patients with this condition. All study patients were evaluated at a multidisciplinary jaw osteonecrosis clinic between June and December 2005. RESULTS: We identified 13 cases, in 12 women and 1 man, with a mean age of 62.6 years. Intravenous amino-bisphosphonate therapy was given for metastatic bone disease from breast cancer in 7 patients and multiple myeloma in 5 patients; the remaining patient was on oral alendronate for osteoporosis. Mean treatment duration was 24 months. A history of dental extraction was found in 11 (84.6%) patients. The mandible was involved in all 13 patients and the maxillary in 3 (23%) patients. Amino-bisphosphonate therapy was discontinued in all 13 patients. We suggest a classification scheme for the clinical and computed-tomography patterns seen in our patients. CONCLUSION: Jaw osteonecrosis is a severe complication of amino-bisphosphonate therapy. In addition to the application of published guidelines, we propose discontinuing bisphosphonate therapy whenever possible. We are evaluating our classification scheme to identify early diagnostic criteria and/or clinical and computed-tomography outcome criteria that would improve the management of patients with jaw osteonecrosis.