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  • 1
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5152-5152
    Abstract: Background. Pamidronate (P) and Zoledronate (Z) are new generation bisphoshonates (BS) used for treatment of bone lesions in patients (pts) with multiple myeloma (MM), solid tumors and no oncologic diseases. They are monthly administered for prolonged periods of time and they are generally well tolerated. Recently, severe osteonecrosis (ON) of the jaw has been reported as an adverse effect of treatment. Avascular bone necrosis has been often observed after major dental procedure. In site of lesion, occasionally, Actinomyces spp were recovered from culture. The aetiology is not understood, although it has been postulated to be secondary to the antiangiogenic effect of BS. Patients. We performed a review of pts of the two hematologic departments treated in the last two years with monthly intravenous BS therapy (Pamidronate 90 mg and /or Zoledronate 4 mg). Overall, 118 patients were studied: 48 males, 70 females; 104 presented MM, 8 severe osteoporosis, 4 iperparathyroidism, 1 Paget disease and 1 breast carcinoma. All patients with a neoplastic disease had received at least one line of chemotherapy. Results. Fourteen pts presented ON (13 with MM and one with severe osteoporosis). The median doses of BS therapy were: 560 mg (range 0–6480 mg) for P, 80 mg (range 0–308 mg) for Z. Five pts had an important exposed jawbone and 11 pts developed ON after a previous tooth extraction. Mandible was involved in 9 pts and maxilla in 5. Diagnosis was made with oral inspection, X-ray, TC and histology. Actinomyces spp were recovered in only one patient. Statistical Analysis. All variables were analyzed for descriptive statistics and to check their distribution by Shapiro-Wilk test. The median values of cumulative dosage were used as cut-off points, and a score 0 was attributed to all dosages lower or equal to median dose, whereas a score 1 was attributed to all dosages grater than median doses. The presence and absence of the event were respectively coded as 1 and 0, and then logistic regression analysis was carried out. The significance for the whole univariate and multivariate models was set at p & lt; 0.05 for the regressors: the odds ratio (OR) was also calculated together with its CI 95%.. At univariate analysis, the significant contributor to oral lesions was only the dosage of pamidronate above or below median value (p=0.021). At multivariate analysis, significant regressors proved to be the female sex (p=0.032; OR 0.142)) and the score of cumulative dosage of drugs (p=0.005; OR 3.977; CI 95%.(OR) 1.517–10.424) Conclusions. Oncologists should pay attention to ON occurrence in long survivors in chronic therapy with BS. Major debridement surgeries are to be avoided if at all possible. Our preliminary data in these pts showed that the lesions are more probable in females than in males and that the administration of more than 560 mg of Pamidronate and of more than 80 mg of Zoledronate is significantly associated with ON lesions.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 2
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 2705-2705
    Abstract: INTRODUCTION: Bisphosphonates (Bsf) are a recognized and effective class of drugs used intravenously to treat cancer-related conditions, such as multiple myeloma (MM) and others solid tumours for the prevention of pathologic fractures, and in oral form to prevent osteoporosis and osteopenia. Some other activities are described as immunomodulating effects. Evolution of bisphosphonates related osteonecrosis of the jaw (BRONJ) is a rare complication with the risk increasing the longer the patient uses the drug. Pamidronate and Zolendronic acid can induce BRONJ in 0,8% – 12% of patients as described in different casistics. In this study we want describe the evolution and outcome of the BRONJ in a multicentric casistic. MATERIAL AND METHODS: In our group we observed 55 pts with Multiple Myeloma (MM) who developed BRONJ; immunoglobulin isotype was: 25 pts IgG-κ; 6 pts IgG-λ, 12 pts IgA-κ; 3 pt IgA-λ, 5 pts IgM-κ, 3 pts MM light chain κ and 1 pt MM light chain λ. Median age was 72 years (range 56–95), male 16/female 39. All patients were treated with Bsf: Pamidronate 1 pts (1,8 %), Zolendronate 36 pts (65,5 %), Pamidronate/zolendronate 18 pts (32,7 %). The average dose of Pamidronate was 2.022 mg (range 90–6.750 mg) and of zoledronate was 84 mg (range 4–256 mg). Anatomic localisation of the BRONJ was: mandible 29 pts (52,7%); maxilla 22 pts (40%); mandible/maxilla 4 cases (7,3 %). The most common trigger for BRONJ was dentoalveolar surgery, including extractions (43 cases-78, 4%), dental implant placement (3 patients-5, 4%), periodontal disease (5 cases-9 %), and in 3 patients with dental prothesis (5, 4%); 1 patient (1,8%) developed BRONJ spontaneously. All patients stopped bsf therapy after BRONJ diagnosis. RESULTS: All patients were treated with conservative treatment such as antibiotic therapy. In 18 patients (32,7%) antibiotic therapy was the only treatment used. Six patients (10,9%) received antibiotic associated with surgical debridement of necrotic bone. Sixteen patients (29%) were treated with antibiotic therapy in combination with hyperbaric oxygen therapy/ozonotherapy and curettage; twelve patients (21, 8%) required sequestrectomy in association with antibiotic and oxygen/hyperbaric therapy. Three patients (5,4%) refused any therapy. Resolution was observed in 19 cases (34,5%); 24 patients (43,6%) improved as pain and as control of infection of the soft and hard tissue. The osteonecrosis was invariated in 9 patients (16,3%); three patients (5, 4%) did not responde to treatment. CONCLUSIONS: Our retrospective study demonstrate that, in established BRONJ, clinical improvement can be obtained in a high percentage (78%), with a complete resolution of bone necrosis in one third of patients. Surgical treatment, associated with antibiotic therapy, is the most effective treatment to eradicate the necrotic bone. The effectiveness of hyperbaric oxygen therapy is not nowadays well determined, but in our experience it demonstrated its utility. Because the most common trigger for BRONJ was dental extractions, prior to treatment with bsf, all patients should have a thorough oral examination and should be completed all invasive dental procedures, achieving optimal periodontal health. With increased recognition and follow up of the BRONJ, it is likely that our knowledge will improve the risk of developing BRONJ and obtaining in more patients a complete remission.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Clinical Lymphoma and Myeloma, Elsevier BV, Vol. 8, No. 2 ( 2008-4), p. 111-116
    Type of Medium: Online Resource
    ISSN: 1557-9190
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2008
    detail.hit.zdb_id: 2193618-3
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  • 4
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2818-2818
    Abstract: Abstract 2818 Poster Board II-794 INTRODUCTION: Bisphosphonate (BSFs) are an effective drug which have been mainly used in oncology for the treatment of solid tumour with bone metastasis, as well as for haematologic disease such as multiple myeloma (MM) and Waldenstrom's Macroglobulinemia (WM), but also prescribed in non neoplastic disease such osteoporosis and Paget's disease. As rare complications related to prolonged treatment with BSFs, an osteonecrosis of the jaw (BRONJ) in neoplastic and non neoplastic diseases is reported with an incidence between 2 and 15% as described in different casitics. The aim of this retrospective multicentric study is to describe the clinical aspects and the evolution of the osteo-necrotic lesions in a long term group of MM patients treated with BSFs. MATERIAL AND METHODS: We studied retrospectively 55 patients (pts) with MM or WM who developed BRONJ followed from January 2003 to January 2009 in different haematological departments. Median age was 72 years (range 56-95), male 16/ 39 female. Immunoglobulin isotype was: 25 pts IgG-κ; 6 pts IgG-α, 12 pts IgA-κ; 3 pts IgA-γ, 5 pts IgM-κ (WM), 3 pts MM light chain κ and 1 pt MM light chain γ. All patients have been treated with BSFs for bone lesions and/or factures: Pamidronate was used in 1 pt (1,8 %), Zolendronic acid in 36 pts (65,5 %), Pamidronate followed by zolendronate in 18 pts (32,7 %). The average dose of Pamidronate was 2.022 mg (range 90-6.750 mg) and of zoledronate was 84 mg (range 4-256 mg). Anatomic localisation of the BRONJ was: mandible 29 pts (52,7%); maxilla 22 pts (40%); mandible/maxilla 4 cases (7,3 %). The most common trigger for BRONJ was dentoalveolar surgery, including extractions (43 cases-78,4%), dental implant placement (3 patients-5,4%), periodontal disease (5 cases-9 %), and in 3 patients with dental prothesis (5,4%); only 1 patient (1,8%) developed BRONJ spontaneously. All patients stopped bsf therapy after BRONJ diagnosis. RESULTS: After a median observation of 26 months (range 1-110 months) no death for BRONJ complication was reported. All patients were treated with conservative treatment such as antibiotic therapy. In 18 patients (32,7%) antibiotic therapy was the only treatment used. Six patients (10,9%) received antibiotic associated with surgical debridement of necrotic bone. Sixteen patients (29%) were treated with antibiotic therapy in combination with ozonotherapy and curettage; twelve patients (21, 8%) required sequestrectomy in association with antibiotic and oxygen/hyperbaric therapy. Three patients (5, 4%) refused any therapy. Among the evaluable patients (53) complete response (CR) was observed in 20 cases (37.75%); partial response (PR) in 21 patients (39.6%) with improving as secondary infection and pain; the clinical finding was unchanged (SD) in 9 patients (16,3%) and 3 patients (5,4%) developed a worsening of the osteonecrosis (PD). CONCLUSIONS: In the unvariate analysis association of surgical treatment with antibiotic therapy, is more effective to eradicate the necrotic bone than antibiotic treatment alone (p= 〈 0.053). O2Iperbaric/Ozonotherapy is a very active treatment, because 44.4% of patient obtain complete resolution of ONJ in comparison to 30.8% of patients who didn't performed this procedure (p= 〈 0.0007). A Multivariate analysis was performed to evaluate differences between variables, but no significant association was found. According to our retrospective study, we confirm that the incidence of this complication is between 2% and 15%, and the cumulative dosage of BSFs is important to induce ONJ. Because the most common trigger for BRONJ was dental extractions, it's an universally recognized indication before BSFs' treatment to implement control of periodontal disease, achieving optimal periodontal health. BRONJ is a late complication of the use of BSFs which interfere on quality of life of patients but not on survival because none death was observed. Disclosures: Petrucci: Ortho Biothec, Jannsen Cilag: Honoraria; Celgene: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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