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1.
J Craniofac Surg ; 28(7): e687-e689, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28857991

RESUMO

Cases of medication-related osteonecrosis of the jaw (MRONJ) have been more commonly associated with aminobiphosphonate therapy than with alkylbiphosphonate treatment. Here, we report a case of MRONJ in a subject who received an alkylbiphosphonate, clodronate, for the treatment of osteoporosis, and discuss the pathogenic mechanisms of alkylbiphosphonates and the possible reasons for the spontaneous and rapid remission of MRONJ occurring in our patient.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Ácido Clodrônico/efeitos adversos , Cicatrização , Idoso , Ácido Clodrônico/uso terapêutico , Feminino , Humanos , Osteoporose/tratamento farmacológico
2.
Ann Oncol ; 27(3): 379-90, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26681681

RESUMO

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients.


Assuntos
Antineoplásicos/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/prevenção & controle , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Osteoporose/prevenção & controle , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/secundário , Quimioterapia Adjuvante , Ácido Clodrônico/efeitos adversos , Ácido Clodrônico/uso terapêutico , Consenso , Difosfonatos/efeitos adversos , Europa (Continente) , Feminino , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Inquéritos e Questionários , Ácido Zoledrônico
3.
Allergol Immunopathol (Madr) ; 43(2): 127-30, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24411095

RESUMO

BACKGROUND: Bisphosphonates are a commonly used class of drugs with known efficacy in the prevention and treatment of postmenopausal and steroid-induced osteoporosis, Paget's disease of bone, hypercaelcemia of malignancy, osteolytic lesions of multiple myeloma, and bone metastases. Nitrogen-containing bisphosphonates have a favourable tolerability and safety profile, cutaneous reactions have been reported. METHODS: This is a retrospective case series study, based on the analysis of data from 1429 patients admitted to the Allergy and Clinical Immunology Division of the University of Messina between January 2011 and December 2012. Most patients had previous adverse drug reactions (ADRs) and referred to us for a challenge test with an alternative drug. RESULTS: We observed six patients with a past history of adverse drug reaction who needed to be tested for bisphosphonates: three patients for risedronate, two for clodronate and one for alendronate. In two years only two patients were referred to us for an adverse reaction to bisphosphonates: one to alendronate and one to risedronate. Another patient presented a previous reaction to strontium ranelate. The other three patients reported previous hypersensitivity reactions to at least two different classes of drugs. All the patients experienced no reaction using the tested drugs. CONCLUSIONS: In our experience drug challenge tests for bisphosphonates are safe and reliable.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Hipersensibilidade a Drogas/diagnóstico , Osteoporose/tratamento farmacológico , Ácido Risedrônico/administração & dosagem , Administração Oral , Idoso , Alendronato/administração & dosagem , Alendronato/efeitos adversos , Ácido Clodrônico/administração & dosagem , Ácido Clodrônico/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/prevenção & controle , Feminino , Antagonistas dos Receptores Histamínicos/administração & dosagem , Humanos , Imunização , Cetoprofeno/administração & dosagem , Cetoprofeno/efeitos adversos , Pessoa de Meia-Idade , Osteoporose/complicações , Estudos Retrospectivos , Testes Cutâneos , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos
4.
Clin Genitourin Cancer ; 13(3): 199-203, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25475039

RESUMO

INTRODUCTION: The aim of the study was to disclose information about the recently incorporated bisphosphonates therapies used to treat prostate cancer patients and their potential risks because the chemical nature and nitrogen content varies among the available drugs on the market. PATIENTS AND METHODS: Three hundred twenty-four consecutive prostate cancer patients were submitted to bisphosphonates therapy after antiandrogen treatment was started. Zoledronic acid was administered monthly (n = 45), bimonthly (n = 15), trimonthly (n = 19), and semestrally (n = 15), and monthly intravenous clodronate was administered in an additional 156 cases. Fourteen additional cases switched the drugs during the course of the treatment. RESULTS: After a median follow-up of 54 ± 24 (control), 63 ± 7 (clodronate), and 54 ± 6 months (zoledronic acid), the only 2 patients (0.6%) who developed osteonecrosis of the jaw (ONJ) occurred in those who switched the drug. CONCLUSION: This study is the longest and the largest ever reported on bisphosphonates usage in prostate cancer patients. ONJ seems to be exclusively related to nitrogen content bisphosphonates.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Ácido Clodrônico/administração & dosagem , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Administração Intravenosa , Idoso , Antagonistas de Androgênios/uso terapêutico , Ácido Clodrônico/efeitos adversos , Ácido Clodrônico/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Esquema de Medicação , Seguimentos , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ácido Zoledrônico
5.
Br J Haematol ; 166(1): 109-17, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24673708

RESUMO

Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long-term follow-up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21-28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5.9-year median follow-up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5.2% vs. CLO 5.8% at 2 years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low, but higher with ZOL (ZOL 3.7% vs. CLO 0.5%; P < 0.0001). ONJ events were generally low grade and most occurred between 8 and 30 months (median time to ONJ, 23.7 months). Among 10 patients with ONJ recovery data, four patients in the ZOL group completely recovered, two patients improved, and three patients experienced no improvement; one CLO patient experienced no improvement. Dental surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal adverse events was similar for ZOL and CLO. ONJ incidence remained low and was lower with CLO compared to ZOL. We have seen no further ONJ cases to date.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Ácido Clodrônico/efeitos adversos , Difosfonatos/efeitos adversos , Imidazóis/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Lesão Renal Aguda/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Ácido Clodrônico/administração & dosagem , Ácido Clodrônico/uso terapêutico , Difosfonatos/administração & dosagem , Difosfonatos/uso terapêutico , Esquema de Medicação , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/epidemiologia , Osteólise/epidemiologia , Osteólise/etiologia , Osteólise/prevenção & controle , Ácido Zoledrônico
6.
J Oral Maxillofac Surg ; 72(3): 503-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24342576

RESUMO

PURPOSE: Osteonecrosis of the jaws is a potential complication of bisphosphonate (BP) therapy. The underlying mechanisms remain unclear. Although most research has concentrated on the effects of BPs on osteoclast and osteoblast functions, the disease is diagnosed and classified based on of mucosal breakdown, suggesting that oral soft tissues may be involved in its pathogenesis. The aim of this study was to determine the effect of 3 different BP drugs (alendronate, zoledronate, and clodronate) on the function of oral keratinocytes and fibroblasts. MATERIALS AND METHODS: Human oral keratinocytes (OKF6) and fetal foreskin fibroblasts (HFFF2) were exposed to each drug at several concentrations and the effect on cell proliferation was assessed by counting the viable cells after different lengths of treatment. The effect on cell migration was examined using Transwell migration assays. An organotypic coculture model using keratinocytes and fibroblasts, which recapitulated the morphology of the oral mucosa, was used to assess the effect of the drugs on epithelial stratification and differentiation. RESULTS: The 3 BPs affected the viability and proliferation of OKF6 and HFFF2 cells at concentrations in keeping with their known relative in vitro potencies. There was no effect on cell migration or tissue architecture in organotypic cultures at subtoxic concentrations. CONCLUSION: The lack of effect of these drugs on cell migration below concentrations known to affect cell viability suggests that BP-related osteonecrosis is not caused through suppression of keratinocyte or fibroblast motility.


Assuntos
Movimento Celular/efeitos dos fármacos , Difosfonatos/efeitos adversos , Fibroblastos/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Alendronato/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ácido Clodrônico/efeitos adversos , Técnicas de Cocultura , Feto , Prepúcio do Pênis/citologia , Prepúcio do Pênis/efeitos dos fármacos , Humanos , Imidazóis/efeitos adversos , Masculino , Mucosa Bucal/citologia , Mucosa Bucal/efeitos dos fármacos , Ácido Zoledrônico
7.
Int J Clin Pharmacol Ther ; 51(4): 313-22, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23357844

RESUMO

BACKGROUND: Clodronate is a bisphosphonate effective in the prevention and treatment of osteoporosis in postmenopausal women. Non-adherence to bisphosphonates, however, is a major issue in clinical practice. Simplifying dose regimens may increase compliance. OBJECTIVES: To assess bioequivalence between an intramuscular (i.m.) clodronate 200 mg/lidocaine 1% twice-a-month formulation and a clodronate 100 mg/lidocaine 1% weekly formulation in 32 postmenopausal women. METHODS: In this double-blind, randomized, two-way crossover study, test and reference formulations were administered in single dose, with a 2-week wash-out between administrations. The primary endpoint was clodronic acid cumulative excretion in the first 24 hours after injection (Xu0-24h). Cumulative excretion in the 72 hours post-dose (Xu0-72h) and maximum excretion rate (Ratemax) were also evaluated. Bioequivalence was assumed if the 90% confidence intervals (CIs) of the geometric means ratios of the dose-normalized parameters were within the 80.00 - 125.00% range. Local tolerability was evaluated. RESULTS: Mean Xu0-24h values were 114.03 ±23.13 mg and 55.22 ±9.73 mg for clodronate 200 mg and 100 mg. The 90% CIs for dose-normalized Xu0-24h, Xu0-72h and Ratemax ere 95 -110%, 94 -107% and 95 - 113%. Local tolerability of both treatments was good. The differences in pain intensity between formulations were not sigificantly different at most assessment times. Headache was the only treatment-related adverse event. CONCLUSIONS: Bioequivalence of the two formulations was confirmed in terms of dose-normalized rate and amount of clodronic acid excretion. This result, together with the favorable tolerability of the novel 200 mg formulation, suggests the possibility of reducing the number of i.m. administrations from once-a-week to twice-a-month.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Ácido Clodrônico/administração & dosagem , Lidocaína/administração & dosagem , Pós-Menopausa , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/farmacocinética , Ácido Clodrônico/efeitos adversos , Ácido Clodrônico/farmacocinética , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Injeções Intramusculares , Lidocaína/efeitos adversos , Lidocaína/farmacocinética , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/prevenção & controle , Equivalência Terapêutica
8.
Drug Des Devel Ther ; 7: 7-12, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23326188

RESUMO

BACKGROUND: Hyaluronic acid has been extensively used for treatment of knee osteoarthritis due to its anti-inflammatory properties and its ability to act as a synovial lubricant. Furthermore, it has found application in combination with other drugs in the dermatological field and in pre-clinical studies in animal models of osteoarthritis. Experimental evidence suggests that a combination of this macromolecule with other drugs may act as a slow-release depot. However, to date, to the best of our knowledge, no one has tested local intra-articular delivery of highly cross-linked hyaluronic acid combined with bisphosphonate or nonsteroidal anti-inflammatory drugs for management of knee osteoarthritis pain in the clinical setting. The aim of the present randomized double-blind study was to investigate, for the first time, the effect of a highly cross-linked hyaluronic acid, Variofill(®), alone or in combination with diclofenac sodium or sodium clodronate, for management of bilateral knee osteoarthritis-related pain. METHODS: Sixty-two patients with symptomatic bilateral medial tibiofemoral knee osteoarthritis (Kellgren-Lawrence grade II and III) and pain in both knees corresponding to a daily visual analog scale (VAS) score ≥ 30 in the month before the beginning of the study were included in this investigation. Patients were divided into three groups: group 1, treated with an injection of hyaluronic acid alone (66 mg) into each knee; group 2, treated with an injection of hyaluronic acid (49.5 mg) plus diclofenac sodium (5 mg) into each knee; group 3, treated with an injection of hyaluronic acid (49.5 mg) plus sodium clodronate (5 mg) into each knee. Patients also underwent blood tests for measurement of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) immediately before and at 6-month follow-up. RESULTS: Hyaluronic acid alone and in combination with sodium clodronate or diclofenac sodium produced a significant improvement in mean VAS pain score at 3 and 6-month follow-up. At 6-month follow-up, therapy with hyaluronic acid plus sodium clodronate was the most beneficial in terms of percentage improvement in VAS pain score. A significant improvement in ESR and CRP was observed at 6-month follow-up in each treatment group. No significant difference was observed when the percentage change from baseline related to these parameters was compared among the groups. No dropout was observed in any group. No serious adverse events were observed. CONCLUSION: Further studies are necessary to determine the effect of a therapy based on hyaluronic acid combined with diclofenac sodium or sodium clodronate in larger cohorts of patients affected by knee osteoarthritis and in longer-term follow-up.


Assuntos
Ácido Clodrônico/uso terapêutico , Diclofenaco/uso terapêutico , Ácido Hialurônico/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Sedimentação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Ácido Clodrônico/administração & dosagem , Ácido Clodrônico/efeitos adversos , Reagentes para Ligações Cruzadas/química , Diclofenaco/administração & dosagem , Diclofenaco/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Dor/tratamento farmacológico , Dor/etiologia , Medição da Dor , Resultado do Tratamento
9.
Lancet Oncol ; 13(7): 734-42, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22704583

RESUMO

BACKGROUND: Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer. METHODS: NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1-3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00009945. FINDINGS: Median follow-up was 90·7 months (IQR 82·7-100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78-1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67-1·05; p=0·13), recurrence-free interval (0·83, 0·67-1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55-1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55-1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57-0·99; p=0·045), bone metastasis-free interval (0·62, 0·40-0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43-0·91; p=0·014), but not for overall survival (0·80, 0·61-1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group; grade 3-4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group. There was one possible case of osteonecrosis of the jaw in the clodronate group. INTERPRETATION: Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. A meta-analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made. FUNDING: National Cancer Institute, Bayer Oy (formerly Schering Oy).


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ácido Clodrônico/uso terapêutico , Administração Oral , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/mortalidade , Ácido Clodrônico/efeitos adversos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade
10.
Blood ; 119(23): 5374-83, 2012 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-22498739

RESUMO

The Medical Research Council Myeloma IX Trial (ISRCTNG8454111) examined traditional and thalidomide-based induction and maintenance regimens and IV zoledronic acid (ZOL) and oral clodronate (CLO) in 1960 patients with newly diagnosed multiple myeloma. Overall survival (OS) and skeletal-related event (SRE) data have been reported for the overall trial population. The present analysis investigated optimal therapy regimens for different patient populations in Myeloma IX. Patients were assigned to intensive or nonintensive treatment pathways and randomized to induction cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) versus cyclophosphamide, thalidomide, and dexamethasone (CTD; intensive) or melphalan and prednisolone versus attenuated oral CTD (CTDa; nonintensive). Patients were also randomized to ZOL or CLO. In the nonintensive pathway, CTDa produced better responses and lower SRE rates than melphalan and prednisolone. ZOL improved OS compared with CLO independently of sex, stage, or myeloma subtype, most profoundly in patients with baseline bone disease or other SREs. In patients treated for ≥ 2 years, ZOL improved OS compared with CLO from randomization (median not reached for either; P = .02) and also from first on-study disease progression (median, 34 months for ZOL vs 27 months for CLO; P = .03). Thalidomide-containing regimens had better efficacy than traditional regimens, and ZOL demonstrated greater benefits than CLO.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas/tratamento farmacológico , Ácido Clodrônico/uso terapêutico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Doenças Ósseas/complicações , Ácido Clodrônico/administração & dosagem , Ácido Clodrônico/efeitos adversos , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Feminino , Seguimentos , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Talidomida/administração & dosagem , Ácido Zoledrônico
11.
J Med Econ ; 15(3): 454-64, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22316275

RESUMO

OBJECTIVE: In the Medical Research Council Myeloma IX Study (MMIX), zoledronic acid (ZOL) 4 mg 3-4/week reduced the incidence of skeletal-related events (SREs), increased progression free survival (PFS), and prolonged overall survival (OS), compared with clodronic acid (CLO) 1600 mg daily, in 1970 patients with newly-diagnosed multiple myeloma (MM). METHODS: An economic model was used to project PFS, OS, the incidence of SREs and adverse events and expected lifetime healthcare costs for patients with newly-diagnosed MM who are alternatively assumed to receive ZOL or CLO. The incremental cost-effectiveness ratio [ICER] of ZOL vs CLO was calculated as the ratio of the difference in cost to the difference in quality-adjusted life years (QALYs). Model inputs were based on results of MMIX and published sources. RESULTS: Compared with CLO, treatment with ZOL increases QALYs by 0.30 at an additional cost of £1653, yielding an ICER of £5443 per QALY gained. If the threshold ICER is £20,000 per QALY, the estimated probability that ZOL is cost-effective is 90%. LIMITATIONS: The main limitation of this study is the lack of data on the effects of zoledronic acid on survival beyond the end of follow-up in the MMIX trial. However, cost-effectiveness was favourable even under the highly conservative scenario in which the timeframe of the model was limited to 5 years. CONCLUSIONS: Compared with clodronic acid, zoledronic acid represents a cost-effective treatment alternative in patients with multiple myeloma.


Assuntos
Conservadores da Densidade Óssea/economia , Ácido Clodrônico/economia , Assistência à Saúde/economia , Difosfonatos/economia , Imidazóis/economia , Mieloma Múltiplo/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Ácido Clodrônico/efeitos adversos , Ácido Clodrônico/uso terapêutico , Análise Custo-Benefício , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida , Reino Unido , Ácido Zoledrônico
12.
Eur J Haematol ; 88(1): 1-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21991938

RESUMO

Osteolytic bone disease is a hallmark of symptomatic multiple myeloma. Bisphosphonates have been the mainstay of treatment to preserve skeletal integrity and prevent skeletal-related events in patients with myeloma-related bone disease. Recently, the MRC Myeloma IX trial demonstrated for the first time improved survival and delayed disease progression with the use of an intravenous amino-bisphosphonate, zoledronic acid, vs. an oral agent, clodronate, with intensive and non-intensive anti-myeloma treatment regimens in patients with newly diagnosed multiple myeloma. These results validate a large body of preclinical, translational and other clinical data suggesting anti-myeloma effects of amino-bisphosphonates. In addition, this trial also provided the first head-to-head evidence for superiority of one bisphosphonate over another (zoledronic acid vs. clodronate) for reducing skeletal morbidity in patients with multiple myeloma, as well as a prospective comparison of toxicities. Despite the use of non-bortezomib containing anti-myeloma treatment regimens in the MRC Myeloma IX trial, these results are encouraging and provide an impetus to continue to evaluate current treatment guidelines for myeloma-associated bone disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Ácido Clodrônico/administração & dosagem , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Osteólise/tratamento farmacológico , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Ensaios Clínicos como Assunto , Ácido Clodrônico/efeitos adversos , Difosfonatos/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Imidazóis/efeitos adversos , Infusões Intravenosas , Masculino , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Osteólise/etiologia , Osteólise/mortalidade , Guias de Prática Clínica como Assunto , Ácido Zoledrônico
13.
Breast Dis ; 33(2): 93-101, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22142660

RESUMO

Bisphosphonates are commonly used in patients with breast cancer to reduce skeletal-related events in metastatic disease and to mitigate bone loss associated with adjuvant therapy. Preclinical studies have shown that bisphosphonates may directly inhibit breast cancer cell proliferation and metastasis. Clinical trials evaluating the oral bisphosphonate clodronate as a component of adjuvant therapy identified a potential reduction in cancer recurrence. Subsequently, trials of zoledronic acid have demonstrated prolonged disease-free survival in postmenopausal or otherwise estrogen-depleted women with early breast cancer. In the ABCSG-12 trial, the addition of twice-yearly zoledronic acid (4 mg IV) to adjuvant endocrine therapy improved disease-free survival in premenopausal women undergoing ovarian suppression. Similar results were observed in postmenopausal women receiving aromatase inhibitors in the ZO-FAST trial, and in women who were at least 5 years past menopause in the AZURE trial. Four recent observational studies (2 cohort studies and 2 case-control analyses) generally support an association between oral bisphosphonate use and lower breast cancer incidence. Ongoing breast cancer adjuvant clinical trials are further evaluating bisphosphonates and, by their influence on contralateral cancers, may provide more evidence regarding the potential of bisphosphonates for breast cancer prevention.


Assuntos
Antineoplásicos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/prevenção & controle , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Antineoplásicos/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/secundário , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Ácido Clodrônico/efeitos adversos , Ácido Clodrônico/uso terapêutico , Difosfonatos/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Incidência , Ácido Zoledrônico
14.
Drug Des Devel Ther ; 5: 445-54, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22087064

RESUMO

Bisphosphonates have a long history in the treatment of osteoporosis and bone-related disease. This review focuses on the use of a specific nonaminobisphosphonate, clodronate, which appears to be much better tolerated than other bisphosphonates and free of high-risk contraindications. Specifically, this paper reviews its use in the prevention of osteoporosis in postmenopausal women, taking into account its tolerability profile and recent safety issues arising regarding the use of bisphosphonates.


Assuntos
Ácido Clodrônico/efeitos adversos , Ácido Clodrônico/uso terapêutico , Difosfonatos/efeitos adversos , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Ácido Clodrônico/economia , Ácido Clodrônico/farmacocinética , Ácido Clodrônico/farmacologia , Difosfonatos/administração & dosagem , Difosfonatos/farmacocinética , Difosfonatos/uso terapêutico , Feminino , Humanos , Masculino , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/prevenção & controle
19.
AJR Am J Roentgenol ; 196(2): 331-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21257884

RESUMO

OBJECTIVE: This article describes the extent and potentially devastating consequences of osteoporosis in adult women. There is discussion of the importance of radiologists in the correct diagnosis and reporting of probable osteoporotic vertebral fractures on medical imaging studies. CONCLUSION: The Genant semiquantitative method for diagnosing osteoporotic vertebral fractures is presented. The importance of dual-energy x-ray absorptiometry reproducibility is also briefly discussed.


Assuntos
Absorciometria de Fóton/métodos , Programas de Rastreamento/métodos , Osteoporose/diagnóstico , Fraturas da Coluna Vertebral/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Calibragem , Ácido Clodrônico/efeitos adversos , Feminino , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/prevenção & controle , Reprodutibilidade dos Testes , Fraturas da Coluna Vertebral/etiologia
20.
Clin Implant Dent Relat Res ; 13(1): 58-63, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19681933

RESUMO

BACKGROUND: In the past few years, the occurrence of an oral lesion, called osteonecrosis of the jaw (ONJ), has been increasingly reported in patients undergoing treatment with bisphosphonates (BPs); however, few published histological studies of ONJ can be found in the literature. PURPOSE: The aim of the present case was to report an occurrence of ONJ after implant insertion. MATERIALS AND METHODS: Multiple myeloma was diagnosed to a 65-year-old female. After 5 years of treatment with intravenous clodronate, two dental implants were inserted in the mandibular molar region. No preexisting bone lesions were present at a preoperative panoramic radiography. Before implant insertion, the patient had suspended the treatment with clodronate for 3 months. Four months after the implant insertion, a breakdown of the oral mucosa covering the implants occurred with a purulent discharge; periapical radiolucency was present around both implants. An en-block resection on the alveolar bone including the two implants was performed. No signs of recurrence of the lesion were observed after a follow-up of 20 months. RESULTS: At the interface of one of the implants, a gap was observed between bone and implant. This bone was nonvital, and many osteocyte lacunae were empty. Moreover, this bone appeared to be partially demineralised. No newly formed bone or osteoblasts were present. Bone trabeculae were observed, on the other hand, within the apical implant threads of the other implant. A close connection was observed between this bone and the implant surface. DISCUSSION: The histological findings showed some areas with osseointegration in patients undergoing BP treatment for malignant disease; however, any invasive procedure can determine the onset of osteonecrosis. CONCLUSION: In conclusion, there is certainly a temporal association between BP use and development of ONJ, but a correlation does not necessarily mean causation. Moreover, generalizations about this complex relationship cannot be made on the basis of a single case report. In patients undergoing intravenous treatment, clinicians must be aware of the increased risk of implant failure and, probably, implant insertion should be avoided at all until more conclusive data are available.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Ácido Clodrônico/efeitos adversos , Implantes Dentários/efeitos adversos , Doenças Mandibulares/patologia , Osteonecrose/patologia , Idoso , Feminino , Humanos , Doenças Mandibulares/etiologia , Osseointegração/efeitos dos fármacos , Osteonecrose/etiologia , Falha de Tratamento
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