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1.
Jpn J Clin Oncol ; 51(1): 100-105, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32869095

RESUMO

PURPOSE: Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. METHODS: Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. RESULTS: Twenty-seven patients were included in the study. The median age was 65 (range, 50-84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0-34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2-89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. CONCLUSION: Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/radioterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Cuidados Paliativos , Ácido Zoledrônico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do Tratamento , Ácido Zoledrônico/farmacologia
2.
Life Sci ; 264: 118681, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129881

RESUMO

Osteoporosis is a bone disease that mainly affects older people and postmenopausal women. Lack of proper treatment for this disease gives rise to many problems in patients and occasionally leads to death. Many drugs have been utilized to treat osteoporosis but the most effective one is the bisphosphonates (BPs) family. This family has several positive effects on bone tissue, including promoting bone healing, enhancing bone mineral density, reducing bone resorption, preventing pathologic fractures, suppressing bone turnover, and modulating bone remodeling. On the other hand, there have also been inconclusive reports that BPs might have a desirable or even adverse impact on osteoporotic patients. Therefore, we set out to examine the positive and negative effects of this family, with a focus on the most potent one that is zoledronate (Zol), in clinical usage. Zoledronate is an amino-BPs and nitrogen-containing drug which is the most powerful BPs on osteoporosis treatment or prevention. Many studies showed its effectiveness in the treatment of osteoporosis and bone healing. As Zol enjoys a considerable potential in treating and preventing osteoporosis, it can be used as one of the effective treatments in this field.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Difosfonatos/farmacologia , Humanos , Osteoporose/metabolismo , Osteoporose/patologia , Resultado do Tratamento , Ácido Zoledrônico/farmacologia
3.
Medicine (Baltimore) ; 99(51): e23637, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371098

RESUMO

ABSTRACT: The main aim of this study is to compare the 2 medications denosumab and zoledronic acid for patients with beta-thalassemia major induced osteoporosis. Patients with B-thalassemia major induced osteoporosis will undergo baseline assessment of the bone densitometry by bone density(DEXA) scan as a standard of care by the radiology department, then a blood test for bone-specific alkaline phosphatase and type-1 collagen telopeptide will be measured by the chemistry laboratory.Patients with B-thalassemia major induced osteoporosis, who are 18 years of age or more and willing to participate in the study will be enrolled after consenting by the primary investigator in hematology outpatient clinics. Patients with osteoporosis will receive 1 of the 2 medications; at the end of the year, DEXA scan will be done to compare the response of the 2 medications. The potential risks include drug-related side effects.The outcome will be measured biochemically by measuring bone-specific alkaline phosphatase and type 1 collagen carboxy telopeptide and radiologically by DEXA scan at baseline and 1 year using Z score.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Osteoporose/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Talassemia beta/complicações , Ensaios Clínicos Fase III como Assunto , Humanos , Osteoporose/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Cochrane Database Syst Rev ; 12: CD013020, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270906

RESUMO

BACKGROUND: Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men with prostate cancer and bone metastases to prevent skeletal-related events (SREs). SREs such as pathologic fractures, spinal cord compression, surgery and radiotherapy to the bone, and hypercalcemia lead to morbidity, a poor performance status, and impaired quality of life. Efficacy and acceptability of the bone-targeted therapy is therefore of high relevance. Until now recommendations in guidelines on which bone-modifying agents should be used are rare and inconsistent. OBJECTIVES: To assess the effects of bisphosphonates and RANKL-inhibitors as supportive treatment for prostate cancer patients with bone metastases and to generate a clinically meaningful treatment ranking according to their safety and efficacy using network meta-analysis. SEARCH METHODS: We identified studies by electronically searching the bibliographic databases Cochrane Controlled Register of Trials (CENTRAL), MEDLINE, and Embase until 23 March 2020. We searched the Cochrane Library and various trial registries and screened abstracts of conference proceedings and reference lists of identified trials. SELECTION CRITERIA: We included randomized controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for men with prostate cancer and bone metastases. We included men with castration-restrictive and castration-sensitive prostate cancer and conducted subgroup analyses according to this criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of trials. We defined proportion of participants with pain response and the adverse events renal impairment and osteonecrosis of the jaw (ONJ) as the primary outcomes. Secondary outcomes were SREs in total and each separately (see above), mortality, quality of life, and further adverse events such as grade 3 to 4 adverse events, hypocalcemia, fatigue, diarrhea, and nausea. We conducted network meta-analysis and generated treatment rankings for all outcomes, except quality of life due to insufficient reporting on this outcome. We compiled ranking plots to compare single outcomes of efficacy against outcomes of acceptability of the bone-modifying agents. We assessed the certainty of the evidence for the main outcomes using the GRADE approach. MAIN RESULTS: Twenty-five trials fulfilled our inclusion criteria. Twenty-one trials could be considered in the quantitative analysis, of which six bisphosphonates (zoledronic acid, risedronate, pamidronate, alendronate, etidronate, or clodronate) were compared with each other, the RANKL-inhibitor denosumab, or no treatment/placebo. By conducting network meta-analysis we were able to compare all of these reported agents directly and/or indirectly within the network for each outcome. In the abstract only the comparisons of zoledronic acid and denosumab against the main comparator (no treatment/placebo) are described for outcomes that were predefined as most relevant and that also appear in the 'Summary of findings' table. Other results, as well as results of subgroup analyses regarding castration status of participants, are displayed in the Results section of the full text. Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants). For this outcome none of the trials reported results for the comparison with denosumab. The adverse event renal impairment probably occurs more often when treated with zoledronic acid compared to treatment/placebo (RR 1.63, 95% CI 1.08 to 2.45; per 1000 participants 78 more (10 more to 180 more); moderate-certainty evidence; network based on 6 trials including 1769 participants). Results for denosumab could not be included for this outcome, since zero events cannot be considered in the network meta-analysis, therefore it does not appear in the ranking. Treatment with denosumab results in increased occurrence of the adverse event ONJ (RR 3.45, 95% CI 1.06 to 11.24; per 1000 participants 30 more (1 more to 125 more); high-certainty evidence; 4 trials, 3006 participants) compared to no treatment/placebo. When comparing zoledronic acid to no treatment/placebo, the confidence intervals include the possibility of benefit or harm, therefore treatment with zoledronic acid probably neither reduces nor increases ONJ (RR 1.88, 95% CI 0.73 to 4.87; per 1000 participants 11 more (3 less to 47 more); moderate-certainty evidence; network based on 4 trials including 3006 participants). Compared to no treatment/placebo, treatment with zoledronic acid (RR 0.84, 95% CI 0.72 to 0.97) and denosumab (RR 0.72, 95% CI 0.54 to 0.96) may result in a reduction of the total number of SREs (per 1000 participants 75 fewer (131 fewer to 14 fewer) and 131 fewer (215 fewer to 19 fewer); both low-certainty evidence; 12 trials, 5240 participants). Treatment with zoledronic acid and denosumab likely neither reduces nor increases mortality when compared to no treatment/placebo (zoledronic acid RR 0.90, 95% CI 0.80 to 1.01; per 1000 participants 48 fewer (97 fewer to 5 more); denosumab RR 0.93, 95% CI 0.77 to 1.11; per 1000 participants 34 fewer (111 fewer to 54 more); both moderate-certainty evidence; 13 trials, 5494 participants). Due to insufficient reporting, no network meta-analysis was possible for the outcome quality of life. One study with 1904 participants comparing zoledronic acid and denosumab showed that more zoledronic acid-treated participants than denosumab-treated participants experienced a greater than or equal to five-point decrease in Functional Assessment of Cancer Therapy-General total scores over a range of 18 months (average relative difference = 6.8%, range -9.4% to 14.6%) or worsening of cancer-related quality of life. AUTHORS' CONCLUSIONS: When considering bone-modifying agents as supportive treatment, one has to balance between efficacy and acceptability. Results suggest that Zoledronic acid likely increases both the proportion of participants with pain response, and the proportion of participants experiencing adverse events However, more trials with head-to-head comparisons including all potential agents are needed to draw the whole picture and proof the results of this analysis.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Neoplasias da Próstata/patologia , Ligante RANK/antagonistas & inibidores , Adulto , Alendronato/efeitos adversos , Alendronato/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Ácido Clodrônico/efeitos adversos , Ácido Clodrônico/uso terapêutico , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Ácido Etidrônico/efeitos adversos , Ácido Etidrônico/uso terapêutico , Humanos , Masculino , Metanálise em Rede , Pamidronato/efeitos adversos , Pamidronato/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Risedrônico/efeitos adversos , Ácido Risedrônico/uso terapêutico , Ácido Zoledrônico/efeitos adversos , Ácido Zoledrônico/uso terapêutico
5.
Bull Cancer ; 107(10): 1019-1023, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32972763

RESUMO

In this review, we report a case of a bone's metastatic breast cancer in Malian patient treated by chemotherapy in whom SRAS-COV-2's diagnosis was made 9days after the onset gastrointestinal symptoms. Patient quickly died before any COVID-19's treatment. According to the poor outcomes of cancer patients with COVID-19, authors emphasize to an intensive attention to such patients in order to find the best therapeutic balance between the two pathologies during this pandemic.


Assuntos
Betacoronavirus , Neoplasias da Mama/complicações , Carcinoma Ductal de Mama/secundário , Infecções por Coronavirus/complicações , Diarreia/etiologia , Pandemias , Pneumonia Viral/complicações , Neoplasias da Coluna Vertebral/secundário , Vômito/etiologia , Adulto , Antineoplásicos Fitogênicos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/complicações , Carcinoma Ductal de Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Evolução Fatal , Feminino , Infecções por HIV/complicações , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/tratamento farmacológico , Tomografia Computadorizada por Raios X , Ácido Zoledrônico/uso terapêutico
6.
Pain Res Manag ; 2020: 8039671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831984

RESUMO

Introduction: This study aimed to compare and analyze the effect of preoperative zoledronic acid (ZOL) administration on pain intensity after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF). Methods: The study included 242 patients with OVCFs who underwent PVP in our hospital between January 2015 and June 2018. The patients were randomly assigned to either a ZOL group (n = 121) or a control group (n = 121). The patients in the ZOL group were treated preoperatively with intravenous infusion of 5 mg ZOL. Those in the control group were treated without ZOL. All the patients were followed up for 1 year. Results: No statistically significant differences in age, sex, weight, and body mass index (BMI) were found between the two groups. During the follow-up period, the visual analog scale score and Oswestry dysfunction index score in the ZOL group were lower than those in the control group. The bone mineral density at 6 or 12 months after treatment was significantly higher and the levels of the bone metabolism markers were significantly lower in the ZOL group than in the control group (P < 0.05 for both). Two patients in the treatment group had new vertebral fractures, whereas 13 patients in the control group had new vertebral fractures, which translate to recompression vertebral fracture incidence rates of 1.7% and 10.7%, respectively. The incidence rate of mild adverse reactions was significantly higher in the ZOL group than in the control group, but all the cases were endurable. Conclusion: Intravenous infusion of ZOL before PVP can effectively reduce postoperative pain intensity, reduce bone loss, increase bone density, reduce the risk of refracture, and improve patient quality of life.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/cirurgia , Dor Pós-Operatória/prevenção & controle , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/efeitos adversos , Ácido Zoledrônico/uso terapêutico , Idoso , Feminino , Fraturas por Compressão/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Qualidade de Vida
7.
Oncology (Williston Park) ; 34(8): 317-319, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32785928

RESUMO

A 78-year-old man had a medical history of hypertension, atrial fibrillation, chronic kidney disease, and metastatic castration-resistant prostate cancer (CRPC). He had progressed to first-line therapy for CRPC with abiraterone plus androgen-deprivation therapy (ADT) and as second-line therapy he was being treated with docetaxel, with biochemical progression in his last prostate specific antigen measurement. He was admitted to the hospital on April 2020, in the middle of the coronavirus disease 2019 (COVID-19) pandemic, because of painful bone lesions and deterioration of renal function.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Infecções por Coronavirus/terapia , Cuidados Paliativos , Pneumonia Viral/terapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Insuficiência Respiratória/terapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Androstenos/uso terapêutico , Antineoplásicos/uso terapêutico , Betacoronavirus , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Dor do Câncer/complicações , Dor do Câncer/terapia , Infecções por Coronavirus/complicações , Progressão da Doença , Docetaxel/uso terapêutico , Combinação de Medicamentos , Definição da Elegibilidade , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Unidades de Terapia Intensiva/provisão & distribução , Lopinavir/uso terapêutico , Masculino , Oxigenoterapia , Pandemias , Pneumonia Viral/complicações , Neoplasias de Próstata Resistentes à Castração/complicações , Neoplasias de Próstata Resistentes à Castração/patologia , Insuficiência Renal , Insuficiência Respiratória/etiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Ácido Zoledrônico/uso terapêutico
8.
J Bone Miner Metab ; 38(6): 894-902, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32656645

RESUMO

INTRODUCTION: Rapid descent in bone mineral density (BMD) and ascent in bone turnover marker (BTM) occur within the short period following denosumab (Dmab) discontinuation. In addition, the incidence of vertebral fracture also rises within the short period. The purpose of this study is to investigate the effects of sequential therapy using zoledronic acid (ZOL) on any adverse events after Dmab discontinuation. MATERIALS AND METHODS: This study was a multicenter retrospective observational study, and the subjects were osteoporosis patients who visited our institutions between 2013 and 2018. We performed sequential therapy using ZOL for 30 patients who had difficulty continuing Dmab, due to physical or social reasons, and investigated the fracture incidence and BMD/BTM changes at 4 time points (at the start of Dmab, the start of ZOL, 6 months after ZOL and 12 months after ZOL). RESULTS: No new vertebral/nonvertebral fractures were observed at each time point after switching from Dmab to ZOL in any of the 30 patients. The BMD/BTM changes were evaluated in 18 of the 30 cases, since all data of lumbar/femoral neck BMDs and TRACP-5b at 4 time points was only available in 18 cases. BMDs significantly increased at each time point compared with that at the start of Dmab. Serum TRACP-5b significantly decreased at each time point compared with that at the start of Dmab. CONCLUSION: It was suggested that sequential therapy using ZOL could suppress the decrease of BMD, and increase of BTM, if the period of Dmab administration was less than 3 years.


Assuntos
Denosumab/uso terapêutico , Suspensão de Tratamento , Ácido Zoledrônico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Denosumab/efeitos adversos , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Estudos Retrospectivos , Fosfatase Ácida Resistente a Tartarato/sangue , Ácido Zoledrônico/efeitos adversos
9.
Medicine (Baltimore) ; 99(25): e20831, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569232

RESUMO

The objective was to investigate the association of different hydration doses and its effect on renal function in patients with primary osteoporosis treated with zoledronic acid.The subjects with primary osteoporosis treated with zoledronic acid at the First Affiliated Hospital of Chongqing Medical University, China, from January 2015 to December 2018 were included in this study. The subjects were classified according to different hydration doses. Renal function indexes before and after treatment were collected and adverse reactions recorded to analyze the changes in renal function associated with different hydration doses.The choice of the hydration dose treated with zoledronic acid deserves attention. The lower hydration dose is, the greater impact on renal function can be caused.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Rim/fisiopatologia , Osteoporose/tratamento farmacológico , Soluções para Reidratação/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Idoso , Conservadores da Densidade Óssea/efeitos adversos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Osteoporose/fisiopatologia , Soluções para Reidratação/administração & dosagem , Estudos Retrospectivos , Ácido Zoledrônico/efeitos adversos
10.
Breast Cancer Res Treat ; 182(2): 381-388, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32474744

RESUMO

BACKGROUND: Skeletal-related events (SREs) are significant contributors to the morbidity and mortality in patients with bone metastasis from breast cancer. Thus, bone-modifying agents (BMAs) are recommended in this population. However, the baseline risk factors of SREs in patients with bone metastasis from breast cancer receiving BMAs are not well understood. METHODS: We analyzed the patient-level data from a controlled arm of a clinical trial comparing denosumab with zoledronate in patients with bone metastases from breast cancer (ClinicalTrial.gov ID: NCT00321464) available at Project Data Sphere, a broad-access research platform that collects and curates patient-level data from completed, phase III cancer trials. The primary endpoint was the first SRE after the inclusion to the trial. The time to the first on study SRE was analyzed using Cox proportional hazards model based on patients' baseline characteristics including age, race, ECOG performance status (PS), histology and immunohistochemistry of breast cancer, and urine and serum laboratory data. RESULTS: Among 756 patients in the zoledronate arm of the trial, we excluded 64 patients with a documented history of osteopenia or osteoporosis. The median age of the patients was 56 years old, the median follow-up was 553 days, and 249 patients (36%) had SREs. The univariate analysis showed that black or African American heritage, ECOG PS > 0, human epidermal growth factor receptor 2 (HER2) positivity, high urine N-telopeptide cross-links / creatinine ratio (NTx/Cre), and elevated serum alkaline phosphatase (ALP) are significant baseline risk factors for SREs. Patients with the characteristics of ECOG PS > 0, HER2 positivity, and elevated ALP also showed a significantly higher hazard ratio of SREs in multivariate analysis. CONCLUSIONS: We determined risk factors for SREs in patients with bone metastasis from breast cancer.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias da Mama/patologia , Fraturas Espontâneas/epidemiologia , Compressão da Medula Espinal/epidemiologia , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias da Mama/mortalidade , Denosumab/uso terapêutico , Intervalo Livre de Doença , Feminino , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/prevenção & controle , Ácido Zoledrônico/uso terapêutico
11.
Curr Opin Oncol ; 32(4): 332-338, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32541321

RESUMO

PURPOSE OF REVIEW: Giant cell tumour of bone (GCTB) is an intermediate, locally aggressive primary bone tumour. In addition to local therapy, new drugs became available for this disease. Denosumab, a receptor activator of nuclear factor κ-B-ligand inhibitor, was introduced as systemic targeted therapy for advanced or inoperable and metastatic GCTB. Also, the bisphosphonate zoledronic acid has activity in GCTB by directly targeting the neoplastic stromal cells. RECENT FINDINGS: In a small RCT, bisphosphonates were successful in controlling tumour growth and a higher apoptotic index of tumour cells was seen after zoledronic acid versus controls. Although bisphosphonate-loaded bone cement has not been studied to a large extent, it does not seem harmful and may constitute a logical local adjuvant. From the largest clinical trial to date, the risk-to-benefit ratio for denosumab in patients with advanced GCTB remains favourable, also in facilitating less morbid surgery. Concerns have arisen that recurrence rates would be higher than after conventional treatment, ranging from 20 to 100% in a systematic review, although this may be because of bias. H3F3A (G34W) driver mutations are helpful in the differentiation between GCTB and other giant cell-containing malignancies. H3.3-G34W proved sufficient to drive tumourigenesis. The cumulative incidence of malignancy in GCTB is estimated at 4%, of which primary malignancy 1.6% and secondary malignancy 2.4%, the latter mainly after radiation. To date, a potential causal relationship between denosumab and pulmonary metastases has not been confirmed; if they do not behave indolently, it would be advised to reassess diagnosis and consider malignancy. SUMMARY: Denosumab remains a highly effective treatment option for patients with advanced GCTB. A short duration of 2-4 months neoadjuvant denosumab is advised to facilitate less morbid surgery and prevent incomplete curettage by macroscopic tumour alterations. Reduced dose intensity is being studied to reduce long term side-effects. Further research on bisphosphonates and other targets including H3.3-G34W remains warranted.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Tumor de Células Gigantes do Osso/patologia , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Terapia Neoadjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Am J Sports Med ; 48(9): 2151-2160, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32543880

RESUMO

BACKGROUND: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. HYPOTHESIS: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro-computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. RESULTS: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head (P = .005) and the medial humeral head (P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head (P = .004) and the medial humeral head (P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group (P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group (r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. CONCLUSION: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. CLINICAL RELEVANCE: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations.


Assuntos
Densidade Óssea , Lesões do Manguito Rotador , Manguito Rotador , Ácido Zoledrônico/uso terapêutico , Animais , Fenômenos Biomecânicos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Cicatrização , Microtomografia por Raio-X
13.
PLoS One ; 15(6): e0234123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492050

RESUMO

We aimed to evaluate the comparative efficacy and safety of drugs respectively for primary prevention and secondary prevention of osteoporotic fractures in postmenopausal women (PMW), and to further identify the optimal intervention(s) respectively for the two groups when efficacy and safety both considered. We searched three databases. Bayesian network meta-analyses were conducted for two efficacy outcomes (vertebral fractures and nonvertebral fractures) and two safety outcomes (tolerability and acceptability) respectively in primary prevention group and secondary prevention group. We synthesized hazard ratios (HRs) and 95% confidence intervals (CIs) for nonvertebral fractures, and risk ratios (RRs) for three others. Factor and cluster analyses on surface under the cumulative ranking curve (SUCRA) values were conducted to identify the best intervention(s) with efficacy and safety both considered. The study protocol has been registered in PROSPERO. We included 57 randomized trials involving fifteen anti-osteoporotic interventions and 106320 PMW. For primary prevention, only zoledronate (once per 18 months) reduced both vertebral (RR 0.46, 95% CI 0.28-0.74) and nonvertebral (HR 0.66, 95% CI 0.51-0.85) fractures. For secondary prevention, abaloparatide, alendronate, denosumab, lasofoxifene, risedronate, romosozumab, teriparatide, and zoledronate (once per 12 months) reduced both vertebral (RRs: from 0.17 to 0.62) and nonvertebral (HRs: from 0.54 to 0.81) fractures. PTH (1-84) and abaloparatide increased withdrawal risk. Romosozumab, teriparatide, denosumab and risedronate, with the greatest composite scores, constituted the optimal cluster having both superior efficacy and superior safety. Zoledronate used at 5 mg per 18 months, with the similar safety as placebo, is the only drug intervention which has been shown to significantly reduce both vertebral and nonvertebral fractures for primary prevention of osteoporotic fractures in PMW; while romosozumab, teriparatide, denosumab, and risedronate are the optimal treatments for secondary prevention when efficacy and safety both considered. A limitation is that safety outcomes failed to consider the severity of adverse effects.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Teorema de Bayes , Conservadores da Densidade Óssea/efeitos adversos , Análise por Conglomerados , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Fraturas por Osteoporose/patologia , Pós-Menopausa , Modelos de Riscos Proporcionais , Risco , Prevenção Secundária , Resultado do Tratamento , Ácido Zoledrônico/efeitos adversos , Ácido Zoledrônico/uso terapêutico
15.
Proc Natl Acad Sci U S A ; 117(22): 12029-12040, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32404427

RESUMO

Hutchinson-Gilford progeria syndrome (HGPS) is a uniformly fatal condition that is especially prevalent in skin, cardiovascular, and musculoskeletal systems. A wide gap exists between our knowledge of the disease and a promising treatment or cure. The aim of this study was to first characterize the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, and to determine the phenotype changes of HGPS mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid. Microcomputed tomography and CT-based rigidity analyses were performed to assess cortical and trabecular bone structure, density, and rigidity. Bones were loaded to failure with three-point bending to assess strength. Contrast-enhanced µCT imaging of mouse femurs was performed to measure glycosaminoglycan content, thickness, and volume of the femoral head articular cartilage. Advanced glycation end products were assessed with a fluorometric assay. The changes demonstrated in the cortical bone structure, rigidity, stiffness, and modulus of the HGPS G608G mouse model may increase the risk for bending and deformation, which could result in the skeletal dysplasia characteristic of HGPS. Cartilage abnormalities seen in this HGPS model resemble changes observed in the age-matched WT controls, including early loss of glycosaminoglycans, and decreased cartilage thickness and volume. Such changes might mimic prevalent degenerative joint diseases in the elderly. Lonafarnib monotherapy did not improve bone or cartilage parameters, but treatment combinations with pravastatin and zoledronic acid significantly improved bone structure and mechanical properties and cartilage structural parameters, which ameliorate the musculoskeletal phenotype of the disease.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Modelos Animais de Doenças , Lamina Tipo A/genética , Progéria , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Fêmur/efeitos dos fármacos , Fêmur/patologia , Glicosaminoglicanos/análise , Articulações/efeitos dos fármacos , Articulações/patologia , Lamina Tipo A/metabolismo , Camundongos , Camundongos Transgênicos , Mutação , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Fenótipo , Piperidinas/uso terapêutico , Pravastatina/uso terapêutico , Progéria/tratamento farmacológico , Progéria/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Piridinas/uso terapêutico , Microtomografia por Raio-X , Ácido Zoledrônico/uso terapêutico
16.
BMJ Case Rep ; 13(4)2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32265210

RESUMO

Meningioma, the second most common primary tumour of the central nervous system, is classified into three different grades based on their characteristics. Each tumour grade includes different molecular subtype, growth potential, and thus, different prognosis. Grade I meningioma is the most common subtype with a benign course, in which systemic dissemination rarely occurs. We present the case of a 48-year-old male patient with a history of grade I meningioma who was referred 3 years after the initial diagnosis to our centre due to pelvic pain. Computed tomography (CT) images showed new pelvic bone lesions whose histopathological report was compatible with a grade I meningioma. Neither hormonal therapy concomitant with octreotide nor hydroxiurea treatments were effective. Very little is known about this entity's prevalence and treatment when disseminated disease occurs. Thus, we think it is important to increase the positive and negative clinical experiences in this setting.


Assuntos
Doenças Ósseas/patologia , Neoplasias Meníngeas/patologia , Meningioma/secundário , Dor Pélvica/etiologia , Antineoplásicos Hormonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas/diagnóstico por imagem , Progressão da Doença , Quimioterapia Combinada , Antagonistas de Estrogênios/uso terapêutico , Evolução Fatal , Humanos , Masculino , Meningioma/classificação , Meningioma/diagnóstico , Meningioma/terapia , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Octreotida/uso terapêutico , Pelve/diagnóstico por imagem , Pelve/patologia , Radioterapia/métodos , Tamoxifeno/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Ácido Zoledrônico/uso terapêutico
17.
JAMA ; 323(15): 1456-1466, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32315057

RESUMO

Importance: A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. Objective: To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. Design, Setting, and Participants: A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. Interventions: Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. Main Outcomes and Measures: The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). Results: Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (-878 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (-11.5 in the zoledronic acid group vs -16.8 in the placebo group; between-group difference, 5.2 [95% CI, -2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (-37.5 vs -58.0, respectively; between-group difference, 20.5 [95% CI, -11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (-33 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. Trial Registration: anzctr.org.au Identifier: ACTRN12613000039785.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças da Medula Óssea/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Medula Óssea/patologia , Doenças da Medula Óssea/complicações , Doenças da Medula Óssea/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/patologia , Falha de Tratamento , Ácido Zoledrônico/administração & dosagem
18.
J Clin Neurosci ; 76: 219-225, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32265080

RESUMO

Whilst surgical resection is traditionally used for the successful eradication of locally aggressive osseous tumors, it is often hazardous or unachievable, particularly in complex anatomic sites, such as the pelvis and spine. The authors present the use of microwave ablation in combination with Zoledronic acid (ZA) administration, alone and with the use of ZA-loaded polymethyl methacrylate (PMMA) to percutaneously treat unresectable bone tumors in 4 patients with giant cell tumors (GCT), multiple myeloma (MM) and breast cancer metastasis.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Cementoplastia/métodos , Micro-Ondas/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Adolescente , Adulto , Idoso , Neoplasias Ósseas/secundário , Feminino , Humanos , Masculino , Mieloma Múltiplo , Pelve , Polimetil Metacrilato , Terapia por Radiofrequência , Coluna Vertebral
19.
Expert Opin Pharmacother ; 21(7): 811-821, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151211

RESUMO

INTRODUCTION: Osteoporosis and subsequent fractures are well-recognized complications of stroke. However, drug treatment strategies for osteoporosis after stroke have been rarely discussed in the current guidelines for the management of stroke or osteoporosis. AREAS COVERED: The authors review the epidemiology, characteristics, pathophysiology, and risk prediction of post-stroke osteoporosis and fractures. Then they provide an overview of existing evidence regarding drug treatment strategies for osteoporosis in stroke patients. They also review the effects on bone mineral density (BMD) and fractures for those drugs commonly used in stroke patients. EXPERT OPINION: Currently, there is scarce evidence. A small randomized control trial suggested that a single use of 4 mg of intravenous zoledronate within 5 weeks of stroke onset was beneficial for preserving BMD, while simultaneous use of calcium and vitamin D supplements may be effective in preventing hypocalcemia. Further studies are needed to address several important issues of post-stroke osteoporosis, including who (the eligibility for treatment), when (the best timing of treatment), what (which drug), and how long (the best duration of treatment). On the other hand, physicians should bear in mind that drugs commonly used for stroke, such as statins or warfarin, may have beneficial or adverse effects on BMD and fracture risks.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Fraturas Ósseas/prevenção & controle , Osteoporose/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Cálcio/uso terapêutico , Suplementos Nutricionais , Feminino , Humanos , Osteoporose/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Vitamina D/uso terapêutico , Ácido Zoledrônico/uso terapêutico
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