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1.
Am J Clin Oncol ; 47(4): 177-184, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38200688

RESUMO

OBJECTIVES: This study evaluated real-world treatment patterns of approved bone-targeting agents (BTAs) with various mechanisms of action-pamidronate, zoledronic acid, and denosumab-for the prevention of skeletal-related events in patients with bone metastases (BM) from solid tumors. METHODS: Adult patients with BM secondary to solid tumors between January 1, 2014, and December 31, 2018, were identified from the Flatiron Health Oncology Services Comprehensive Electronic Records database and categorized by BTA use and therapy type. Time from diagnosis to initiation, persistence (mean time on treatment), and compliance (≥12 administrations/year) with BTA with up to 4 years of follow-up were examined. RESULTS: This study included 27,268 patients with BM (breast cancer, 32.7%; lung cancer, 16.5%; prostate cancer, 17.2%; and other solid tumors, 33.6%); of these, 41.4% initiated denosumab after BM diagnosis; 21.3%, zoledronic acid; 0.6%, pamidronate; and 36.7% had no treatment record. Mean (SD) time to initiation for denosumab or zoledronic acid was 68.6 (157.0) days (denosumab, 70.3 (160.4) days; zoledronic acid, 65.2 [150.2] days). Mean persistence and compliance (first year of treatment) were significantly higher for denosumab than for zoledronic acid (22.0 vs. 14.9 mo [ P <0.0001] and 42.3% vs. 34.8% [ P <0.0001], respectively). Treatment compliance was the highest in patients with breast cancer (denosumab, 48.2%; zoledronic acid, 39.1%). CONCLUSION: Real-world BTA treatment patterns in the United States suggest that over one-third of patients with BM secondary to solid tumors remain untreated and less than 50% of the patients received ≥12 administrations/year of BTA therapy.


Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Neoplasias da Mama , Masculino , Humanos , Estados Unidos , Ácido Zoledrônico/uso terapêutico , Denosumab/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Pamidronato/uso terapêutico , Registros Eletrônicos de Saúde , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Difosfonatos/uso terapêutico
2.
Cochrane Database Syst Rev ; 1: CD002010, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36625789

RESUMO

BACKGROUND: Osteoporosis is a disorder of bone mineralisation occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and decrease the risk of new fractures in post-menopausal women and people receiving long-term oral corticosteroids. This is an updated version of a previous review. OBJECTIVES: To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, trial withdrawals, and survival in people with cystic fibrosis. SEARCH METHODS: We searched the Cystic Fibrosis and Genetic Disorders Group's Trials Register of references (identified from electronic database searches and hand searches of journals and abstract books) on 5 May 2022. We performed additional searches of PubMed, clinicaltrials.gov and the WHO ICTRP (International Clinical Trials Registry Platform) on 5 May 2022. SELECTION CRITERIA: Randomised controlled trials of at least six months duration studying bisphosphonates in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Authors independently selected trials, extracted data and assessed risk of bias in included studies. Trial investigators were contacted to obtain missing data. We judged the certainty of the evidence using GRADE. MAIN RESULTS: We included nine trials with a total of 385 participants (272 adults and 113 children (aged five to 18 years)). Trial durations ranged from six months to two years. Only two of the studies were considered to have a low risk of bias for all the domains.  Bisphosphonates compared to control in people with cystic fibrosis who have not had a lung transplant Seven trials included only adult participants without lung transplants, one trial included both adults and children without lung transplantation (total of 238 adults and 113 children). We analysed adults (n = 238) and children (n = 113) separately. Adults Three trials assessed intravenous bisphosphonates (one assessed pamidronate and two assessed zoledronate) and five trials assessed oral bisphosphonates (one assessed risedronate and four assessed alendronate). Bisphosphonates were compared to either placebo or calcium (with or without additional vitamin D). Data showed no difference between treatment or control groups in new vertebral fractures at 12 months (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.02 to 2.09; 5 trials, 142 participants; very low-certainty evidence) and two trials (44 participants) reported no vertebral fractures at 24 months. There was no difference in non-vertebral fractures at 12 months (OR 2.11, 95% CI 0.18 to 25.35; 4 trials, 95 participants; very low-certainty evidence) and again two trials (44 participants) reported no non-vertebral fractures at 24 months. There was no difference in total fractures between groups at 12 months (OR 0.57, 95% CI 0.13 to 2.50; 5 trials, 142 participants) and no fractures were reported in two trials (44 participants) at 24 months. At 12 months, bisphosphonates may increase bone mineral density at the lumbar spine (mean difference (MD) 6.31, 95% CI 5.39 to 7.22; 6 trials, 171 participants; low-certainty evidence) and at the hip or femur (MD 4.41, 95% 3.44 to 5.37; 5 trials, 155 participants; low-certainty evidence). There was no clear difference in quality of life scores at 12 months (1 trial, 47 participants; low-certainty evidence), but bisphosphonates probably led to more adverse events (bone pain) at 12 months (OR 8.49, 95% CI 3.20 to 22.56; 7 trials, 206 participants; moderate-certainty evidence). Children The single trial in 113 children compared oral alendronate to placebo. We graded all evidence as low certainty. At 12 months we found no difference between treatment and placebo in new vertebral fractures (OR 0.32, 95% CI 0.03 to 3.13; 1 trial, 113 participants) and non-vertebral fractures (OR 0.19, 95% CI 0.01 to 4.04; 1 trial, 113 participants). There was also no difference in total fractures (OR 0.18, 95% CI 0.02 to 1.61; 1 trial, 113 participants). Bisphosphonates may increase bone mineral density at the lumbar spine at 12 months (MD 14.50, 95% CI 12.91 to 16.09). There was no difference in bone or muscle pain (MD 3.00, 95% CI 0.12 to 75.22), fever (MD 3.00, 95% CI 0.12 to 75.22) or gastrointestinal adverse events (OR 0.67, 95% CI 0.20 to 2.26). The trial did not measure bone mineral density at the hip/femur or report on quality of life.  Bisphosphonates compared to control in people with cystic fibrosis who have had a lung transplant One trial of 34 adults who had undergone lung transplantation compared intravenous pamidronate to no bisphosphonate treatment. It did not report at 12 months and we report the 24-month data (not assessed by GRADE). There was no difference in the number of fractures, either vertebral or non-vertebral. However, bone mineral density increased with treatment at the lumbar spine (MD 6.20, 95% CI 4.28 to 8.12) and femur (MD 7.90, 95% CI 5.78 to 10.02). No participants in either group reported either bone pain or fever. The trial did not measure quality of life. AUTHORS' CONCLUSIONS: Oral and intravenous bisphosphonates may increase bone mineral density in people with cystic fibrosis, but there are insufficient data to determine whether treatment reduces fractures. Severe bone pain and flu-like symptoms may occur with intravenous bisphosphonates. Before any firm conclusions can be drawn, trials in larger populations, including children, and of longer duration are needed to determine effects on fracture rate and survival. Additional trials are needed to determine if bone pain is more common or severe (or both) with the more potent zoledronate and if corticosteroids can ameliorate or prevent these adverse events. Future trials should also assess gastrointestinal adverse effects associated with oral bisphosphonates.


Assuntos
Conservadores da Densidade Óssea , Fibrose Cística , Fraturas Ósseas , Dor Musculoesquelética , Osteoporose , Fraturas da Coluna Vertebral , Adulto , Criança , Feminino , Humanos , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Difosfonatos/efeitos adversos , Fraturas Ósseas/prevenção & controle , Dor Musculoesquelética/induzido quimicamente , Osteoporose/tratamento farmacológico , Pamidronato/uso terapêutico , Qualidade de Vida , Ácido Zoledrônico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Technol Health Care ; 31(4): 1343-1353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36641696

RESUMO

BACKGROUND: The pulsed electromagnetic fields (PEMFs) seem effective in increasing bone mineral density and promoting osteogenesis and bone healing. OBJECTIVE: To examine the effect of two different modalities of PEMFs therapy in comparison with the recommended pharmacological treatment on experimental osteoporosis in rats. METHODS: The experimental model of estrogen-deficient osteoporosis induced by ovariectomy was used in this study. The animals were exposed to PEMFs of various frequencies (40 Hz and 25 Hzk), intensities (10 mT and 36.4 µT), lengths of exposure, and the effects were compared with the standard treatment with pamidronate, vitamin D, and calcium supplementation. RESULTS: The application of PEMF40Hz, significantly reduced the osteoporotic bone loss in female rats that were confirmed with biochemical, biomechanical, and histological analyses. These effects were more pronounced than in osteoporotic animals treated with pamidronate, vitamin D, and calcium supplementation. On the contrary, the exposure to PEMF25Hz did not show restorative effects but led to further progression of osteoporosis. CONCLUSION: The exposure to PEMF40Hz, significantly restored osteoporosis and attenuated bone fragility in comparison to the rats exposed to PEMF25Hz or those treated with pamidronate, vitamin D, and calcium supplementation.


Assuntos
Cálcio , Campos Eletromagnéticos , Estrogênios , Osteoporose , Pamidronato , Vitamina D , Animais , Feminino , Ratos , Densidade Óssea/efeitos dos fármacos , Cálcio/farmacologia , Cálcio/uso terapêutico , Campos Eletromagnéticos/efeitos adversos , Estrogênios/deficiência , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Pamidronato/uso terapêutico , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico
4.
BMJ Case Rep ; 16(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599493

RESUMO

A girl in middle childhood was referred to rheumatology with a 1-month history of progressive skull pain, preceded by fleeting musculoskeletal symptoms. Apart from a scaly rash on her scalp, she was well, with moderately elevated inflammatory markers. Skull imaging (radiographs, CT and MRI) revealed osteolytic lesions, soft tissue swelling and pachymeningeal enhancement at frontal and temporal convexities. Langerhans cell histiocytosis, bone infection/inflammation or malignancy was considered. Skin and bone biopsies eventually ruled out mimicking diseases and confirmed the diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). She was treated with intravenous pamidronate (IVPAM) for 9 months, with rapid resolution of pain and gradual resolution of bony abnormalities. She remains in remission at 15-month follow-up. While CRMO can affect any bone, skull involvement is extremely rare, with a broad differential diagnosis. We recommend bone biopsy to confirm skull CRMO. The patient achieved excellent clinical and radiological response to IVPAM.


Assuntos
Osteíte , Osteomielite , Feminino , Criança , Humanos , Diagnóstico Diferencial , Osteomielite/diagnóstico por imagem , Osteomielite/tratamento farmacológico , Pamidronato/uso terapêutico , Imageamento por Ressonância Magnética , Dor/diagnóstico , Crânio/diagnóstico por imagem , Crânio/patologia , Doença Crônica
5.
JAMA ; 328(16): 1624-1636, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36282253

RESUMO

Importance: Hypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (<3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (>3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma. Observations: Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival. Conclusions and Relevance: Mild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.


Assuntos
Hipercalcemia , Hiperparatireoidismo Primário , Hormônio Paratireóideo , Humanos , Cálcio/sangue , Coma/etiologia , COVID-19/complicações , Desidratação/etiologia , Desidratação/terapia , Denosumab/efeitos adversos , Hipercalcemia/sangue , Hipercalcemia/etiologia , Hipercalcemia/terapia , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Náusea/etiologia , Neoplasias/sangue , Neoplasias/complicações , Pamidronato/uso terapêutico , Hormônio Paratireóideo/sangue , SARS-CoV-2 , Sonolência , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Vitamina A/efeitos adversos , Vitamina D/efeitos adversos , Vômito/etiologia , Ácido Zoledrônico/uso terapêutico
6.
Biomater Sci ; 10(20): 6037-6048, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36073144

RESUMO

In the process of bone metastasis, tumor cells spread to the bones to activate osteoclasts, which cause pathological bone resorption and destruction. Bisphosphonates (BPs) inhibit osteoclast activation to resorb bone, reducing bone pain and fracture. We previously developed a nanocomposite for potential localized treatment of bone metastasis by loading a BP compound, ibandronate, onto oxidized carbon nanohorns (OxCNHs), a next-generation drug carrier, using calcium phosphates (CaPs) as mediators to generate OxCNH-CaP-BP nanocomposites. The objective of the present study was to determine nanocomposite formation and biological properties of nanocomposites constructed from two BPs, zoledronate and pamidronate. In vitro tests using murine macrophages (RAW264.7 cells) and osteoclasts differentiated from RAW264.7 cells revealed that the resulting OxCNH-CaP-BP nanocomposites suppressed cell viability in a BP type-dependent manner and more effectively than OxCNHs or BPs alone. The mechanism for the potent and BP type-dependent suppression of cell viability by OxCNH-CaP-BP nanocomposites, based on their relative cellular uptake and reactive oxygen species generation, is also discussed. The present study supports the conclusions that BPs can be loaded onto OxCNHs using CaPs as mediators, and that OxCNH-CaP-BP nanocomposites are putative medicines for localized treatment of metastatic bone destruction.


Assuntos
Neoplasias Ósseas , Reabsorção Óssea , Nanocompostos , Animais , Fosfatos de Cálcio/farmacologia , Carbono/farmacologia , Sobrevivência Celular , Difosfonatos/farmacologia , Portadores de Fármacos/farmacologia , Ácido Ibandrônico/farmacologia , Ácido Ibandrônico/uso terapêutico , Camundongos , Osteoclastos , Pamidronato/farmacologia , Pamidronato/uso terapêutico , Espécies Reativas de Oxigênio/farmacologia , Ácido Zoledrônico/farmacologia , Ácido Zoledrônico/uso terapêutico
7.
Clin Immunol ; 238: 109018, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35460903

RESUMO

Chronic nonbacterial osteomyelitis (CNO) can cause significant morbidity, including bone pain and damage. In the absence of clinical trials, treatments include non-steroidal anti-inflammatory drugs, corticosteroids, TNF-inhibitors (TNFi) and/or bisphosphonates. In a retrospective chart review in the United Kingdom and Germany, we investigated response to TNFi and/or pamidronate. Ninety-one patients were included, receiving pamidronate (n = 47), TNFi (n = 22) or both sequentially (n = 22). Patients with fatigue [p = 0.003] and/or arthritis [p = 0.002] were more frequently treated with TNFi than pamidronate. Both therapies were associated with clinical remission at 6 months, and reduction of bone lesions on MRI at 12 months. While not reaching statistical significance, pamidronate resulted in faster resolution of MRI lesions. Fewer flares were observed with TNFi. Failure to respond to pamidronate was associated with female sex [p = 0.027], more lesions on MRI [p = 0.01] and higher CRP levels [p = 0.03]. Randomized clinical trials are needed to confirm observations and generate evidence.


Assuntos
Difosfonatos , Osteomielite , Difosfonatos/uso terapêutico , Feminino , Humanos , Osteomielite/tratamento farmacológico , Osteomielite/patologia , Pamidronato/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral
9.
Support Care Cancer ; 30(9): 7047-7051, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35312858

RESUMO

Antiresorptive drugs (bisphosphonates and denosumab) have become the cornerstone of medical supportive treatment of bone metastases in solid cancer patients. In the beginning, the choice of available antiresorptive agents was limited to bisphosphonates and the treatment options restricted principally to monthly pamidronate and monthly zoledronic acid. Introduction of new antiresorptive therapies (monthly denosumab) and schedules (zoledronic acid every 3 months, upfront or after initial period of monthly infusion) in the last decade increased the range of available options, thus challenging treatment decision making. Direct and indirect costs of very different treatment options are difficult to interpret in a global cost-benefit analysis. In addition, awareness of the increased risk of medication-related osteonecrosis of the jaw (MRONJ) in bone metastatic cancer patients receiving long-term antiresorptive medications is likely to influence therapy choice in the real-life scenario. We discuss the possible threat of MRONJ risk underestimation and the need for long-term risk stratification of patients based on actuarial data, the role of bisphosphonates and denosumab in that scenario, and the emerging role of surgical therapy to successfully cure MRONJ, in the light of the improved quality of life and survival of patients with bone metastases from solid cancers.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Neoplasias Ósseas , Denosumab , Difosfonatos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Análise Custo-Benefício , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Humanos , Pamidronato/uso terapêutico , Qualidade de Vida , Medição de Risco , Ácido Zoledrônico/uso terapêutico
10.
Arch Osteoporos ; 17(1): 28, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35106633

RESUMO

Pseudomyogenic hemangioendothelioma (PMH) can be a challenge for diagnosis and might be confused with other tumors, such as epithelioid sarcoma. Here we present a case and a systematic review of the literature to identify and discuss PMH treatment in primary bone involvement. A 25-year-old woman was referred for bone pain (10/10) in the left lower limb. Magnetic resonance imaging (MRI) showed multiple bone lesions (left femur, tibia, patella, ankle, and foot) with well-defined borders without signs of local aggressiveness. Positron Emission Tomography-Computed Tomography (PET-CT) showed multiple metabolic musculoskeletal lesions in the left lower limb. A CT scan-guided biopsy was performed. Histological and immunohistochemical findings confirmed the diagnosis of PMH. After treatment with intravenous pamidronate (90 mg/monthly), the patient had clinical improvement, mild pain 2/10 without the use of non-steroidal anti-inflammatory drugs or opiates. Follow-up was assessed by MRI and PET-CT. PET-CT showed metabolic resolution of most of the bone and muscular lesions and a significant improvement of the femoral lesion. MRI showed that the lesions in the left femur, tibia, and foot had a marked decrease in size without intravenous post-contrast enhancement and smaller lesions had disappeared. After a 3-year follow-up, PET-CT showed no metabolically active images. Literature review identified 31 records including 58 clinical cases of PMH with primary bone involvement and treatment description for qualitative analysis. Most lesions (69%) were treated by local excision or curettage. In addition, amputations were performed in a significant percentage of cases (20.7%). In the last years, mTOR inhibitors (n = 7) and anti-resorptive treatments (n = 4) were considered as alternative treatment options, especially in multifocal lesions.


Assuntos
Hemangioendotelioma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Osso e Ossos/patologia , Feminino , Hemangioendotelioma/patologia , Hemangioendotelioma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Pamidronato/uso terapêutico
11.
Arch Pediatr ; 29(2): 153-156, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35039190

RESUMO

Congenital mesoblastic nephroma is a rare pediatric renal tumor and has been reported in patients presenting with palpable abdominal mass, arterial hypertension, hematuria, polyuria, or hypercalcemia. Here we present the case of a 1-month-old neonate with suspected parathyroid hormone (PTH)-related peptide (PTH-rp)-mediated severe hypercalcemia revealing congenital mesoblastic nephroma. Preoperatively, hypercalcemia was corrected with hydration, furosemide, pamidronate, and low-calcium infant formula. Unilateral nephrectomy led to the resolution of hypercalcemia, transient hyperparathyroidism, and transient vitamin D and mineral supplementation. We conclude that congenital mesoblastic nephroma can secrete PTH-rp that can cause severe hypercalcemia.


Assuntos
Hipercalcemia/congênito , Neoplasias Renais/congênito , Nefroma Mesoblástico/congênito , Cálcio/sangue , Feminino , Alimentos Fortificados , Furosemida/uso terapêutico , Humanos , Hipercalcemia/etiologia , Hipercalcemia/terapia , Hipertensão , Fórmulas Infantis , Recém-Nascido , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Nefrectomia , Nefroma Mesoblástico/complicações , Nefroma Mesoblástico/cirurgia , Pamidronato/uso terapêutico , Resultado do Tratamento
12.
Bone ; 158: 115901, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33631354

RESUMO

Bone metastatic disease may lead to serious adverse events in patients with cancer. Bone-directed therapies, including bisphosphonates such as pamidronate and zoledronic acid and the human monoclonal antibody denosumab, are currently approved for the prevention of bone-related adverse events. However, despite the benefits of these drugs, they may cause side effects that are mostly associated with dosages and treatment durations. These side effects range from more frequent, mostly mild, and generally self-limited side effects-such as fever, myalgias, arthralgias, and electrolyte imbalances-to less frequent and more severe side effects such as medication-related osteonecrosis of the jaw and atypical femoral fractures. The purpose of this review is to familiarize clinicians with the literature regarding adverse events associated with bone-directed therapies in patients with cancer. It is important to be aware of these possible adverse events and to educate patients about the predisposing factors associated with side effects from bone-directed therapies and the preventive measures necessary to decrease the risk of occurrence.


Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Anticorpos Monoclonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Humanos , Pamidronato/uso terapêutico , Ácido Zoledrônico/uso terapêutico
13.
Lymphat Res Biol ; 20(2): 118-124, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34435889

RESUMO

Background: Complex lymphatic anomalies (CLA) are a group of conditions that pose diagnostic and therapeutic challenges due to their rarity and overlapping clinical findings. This case series describes the complex pathology and novel combination therapies of three patients diagnosed with various types of CLA. Methods and Results: A retrospective review of medical records was performed for three patients treated for CLA between 2011 and 2019. Diagnostics, imaging, treatment, and follow-up were reviewed in the electronic medical record and combined with the literature review within the analysis. One patient had involvement of her skull base and ear canals, diagnosed after ear canal abnormalities were detected on computed tomography following meningitis. The second patient had involvement of her posterior ribs and T7-T12 vertebral bodies, with thoracic instability requiring a back brace. The third patient had involvement of his left lower extremity and hemipelvis, necessitating a left above the knee amputation. Case 1 progressed on sirolimus and pamidronate but responded to zoledronic acid (ZA). She developed flares of coagulopathy and cellulitis that required reinforcement with vincristine and steroid pulses. Similarly, case 2 progressed on sirolimus and ZA alone, but achieved stable disease with added vincristine. Upon further disease progression, stabilization was obtained by the reinforcement of ZA. Case 3 required a combination of surgery as well as medical management with sirolimus and pamidronate. All three patients now have stable disease. Conclusion: This case series depicts a multidisciplinary and multiagent approach to the management of CLA with severe bony involvement using sirolimus, bisphosphonates, vincristine, and steroids.


Assuntos
Doenças Ósseas , Anormalidades Linfáticas , Doenças Ósseas/induzido quimicamente , Doenças Ósseas/tratamento farmacológico , Feminino , Humanos , Anormalidades Linfáticas/complicações , Anormalidades Linfáticas/diagnóstico por imagem , Anormalidades Linfáticas/tratamento farmacológico , Pamidronato/uso terapêutico , Sirolimo/uso terapêutico , Vincristina/uso terapêutico
14.
J Clin Endocrinol Metab ; 106(11): e4593-e4602, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34157125

RESUMO

CONTEXT: Bisphosphonates are effective for hypercalcemia of malignancy (HOM). Efficacy and safety data for bisphosphonates in parathyroid hormone-related hypercalcemia (PTHRH) are rare, including pamidronate (Pam), which is not indicated for this condition. OBJECTIVE: This work aims to evaluate the efficacy and safety of Pam for moderate-to-severe PTHRH. METHODS: This retrospective case-control study was conducted at a tertiary care medical center. Patients included adults hospitalized with serum calcium levels greater than 12 mg/dL, from October 29, 2013 to December 17, 2019. Etiology was categorized as PTHRH or PTH-independent. Clinical and laboratory data of PTHRH patients treated with Pam (PTHRH-Pam+) were compared to Pam-untreated counterparts (PTHRH-Pam-). RESULTS: Thirty-four patients with 37 hospitalizations for PTHRH (Pam-treated and -untreated) met the inclusion criteria. Pam was given in 24 of 37 cases (64.8%). Admission serum calcium levels for the PTHRH-Pam+ group were higher than for PTHRH-Pam- group (14.4 mg/dL vs 13.0 mg/dL, P = .005). Median total Pam dose was 60 mg (range, 30-180 mg) in the treated group. Serum calcium decreased 3.5 mg/dL for PTHRH-Pam+ vs 1.6 mg/dL for PTHRH-Pam- (P = .003). No PTHRH-Pam+ patients developed hypocalcemia or acute kidney injury. Nadir serum phosphorus levels were lower in the PTHRH-Pam+ vs PTHRH-Pam- group (1.7 mg/dL vs 2.4 mg/dL, respectively, P = .004). Three PTHRH-Pam+ patients developed severe hypophosphatemia; all resolved with intravenous and oral supplementation. Seventeen patients underwent parathyroidectomy, of whom 10 received Pam within 28 days preoperatively. Postoperatively, 4 developed hypocalcemia and 3 hypophosphatemia. CONCLUSION: This study demonstrates that Pam is effective and safe for treating PTHRH, while ensuring close laboratory monitoring of calcium and phosphorus metabolism. Larger, prospective studies are needed to establish the role of Pam and other potent bisphosphonates in moderate-to-severe PTHRH.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Cálcio/sangue , Hospitalização/estatística & dados numéricos , Hipercalcemia/tratamento farmacológico , Pamidronato/uso terapêutico , Hormônio Paratireóideo/metabolismo , Administração Intravenosa , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Hipercalcemia/metabolismo , Hipercalcemia/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Sultan Qaboos Univ Med J ; 21(1): e127-e131, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33777435

RESUMO

Paget's disease of bone (PDB) is a focal disorder of accelerated skeletal remodelling that is uncommon in patients under the age of 40 years; it is more prevalent in older individuals. We report two cases of PDB diagnosed in early adulthood at the Mohamed Kassab Institute of Orthopedics, La Manouba, Tunisia. The first case was a 35-year-old male patient who presented in 2011 with a seven-month history of hip pain. The second case was a 39-year-old female patient who presented 2014 with chronic lower back pain. The PDB diagnosis was confirmed with clinical, biological and radiological investigations. Both patients were doing well on follow-up. Some previous cases have been reported in the literature, differing from the presented cases in some aspects; data of PDB features at differing ages is still insufficient. Early recognition of this clinical entity in young patients is important as early treatment can affect the progression of the disease.


Assuntos
Adenocarcinoma , Osteíte Deformante/diagnóstico , Adulto , Fosfatase Alcalina/sangue , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Osteíte Deformante/diagnóstico por imagem , Pamidronato/uso terapêutico , Cintilografia , Tomografia Computadorizada por Raios X
16.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542026

RESUMO

Osteogenesis imperfecta (OI) consists of a group of genetically and phenotypically heterogeneous diseases characterised by bone fragility. Recent improvement in gene sequencing methods has helped us identify rare forms of OI that are inherited in an autosomal recessive manner. Paediatric endocrinology was consulted on a newborn girl with multiple fractures and wavy thin ribs noted on X-rays. In addition to the bone phenotype, she also has short stature and recurrent acute liver failure (ALF) episodes triggered by intercurrent illness. Whole exome sequencing revealed two novel compound heterozygous variants in neuroblastoma amplified sequence (NBAS) gene. NBAS gene codes for a protein that is involved in nonsense-mediated decay pathway and retrograde transport of proteins from Golgi to endoplasmic reticulum. Recognition of pathogenic variants in this gene as a rare cause of autosomal recessive OI and recurrent ALF has important therapeutic implications.


Assuntos
Heterozigoto , Falência Hepática Aguda/genética , Proteínas de Neoplasias/genética , Osteogênese Imperfeita/genética , Conservadores da Densidade Óssea/uso terapêutico , Nanismo/genética , Feminino , Humanos , Lactente , Recém-Nascido , Osteogênese Imperfeita/tratamento farmacológico , Pamidronato/uso terapêutico , Fenótipo , Recidiva , Sequenciamento do Exoma
17.
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
18.
Indian Pediatr ; 57(1): 75-76, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31937708

RESUMO

Juvenile dermatomyositis is a rare systemic autoimmune disease wth calcinosis as its hallmark sequelae. We report three patients with juvenile dermatomyositis with calcinosis, who were treated with pamidronate. There was complete clearance of calcinosis in one child.


Assuntos
Calcinose , Dermatomiosite/complicações , Pamidronato/uso terapêutico , Calcinose/tratamento farmacológico , Calcinose/etiologia , Calcinose/patologia , Criança , Pré-Escolar , Feminino , Dedos/patologia , Humanos , Masculino
19.
Pediatr Rheumatol Online J ; 18(1): 4, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941491

RESUMO

BACKGROUND: Studies evaluating treatment responses for chronic nonbacterial osteomyelitis (CNO) are lacking. We aimed to measure and compare response rates of medical treatments, time to response of medical treatments among patients with CNO of the mandible, and describe bacterial contamination rates from biopsy. METHODS: We conducted a retrospective chart review of all patients diagnosed with CNO of mandible between 2003 and 2017 and extracted demographic, clinical, laboratory, imaging and surgical data. Detailed medication use and response to medications were recorded. The primary outcome was response to medical treatments defined as improvement of presenting symptoms, inflammatory markers, and imaging if available. Medical treatments included nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti rheumatic drugs (DMARDs), anti-tumor necrosis factor (TNF) therapy, and pamidronate. Descriptive analysis was performed when appropriate. Multivariable logistic regression and Kaplan-Meier curves were applied to compare the responses to medical treatments and time to full response. RESULTS: We identified 22 patients with a median age of 11 and 36% were female. Four patients (18%) had multifocal bone lesions. CT findings (n = 21) showed lytic lesions (62%) and sclerosis (90%). MRI (n = 14) revealed hyperintensity within bone marrow (100%), soft tissue (71%) and bony expansion (71%). Non-antibiotic treatments including NSAIDs (n = 18), glucocorticoids (n = 10), DMARDs (n = 9), anti-TNF therapy (n = 5) and pamidronate (n = 6) were applied. Rates of full responses to anti-TNF therapy (60%) and pamidronate (67%) were higher than that to NSAIDs (11%) (p < 0.05). Patients receiving pamidronate responded more rapidly than those receiving anti-TNF therapy (median two vs 17 months, p = 0.01) when there was a full response. All had bone biopsies. Intraoral biopsy was performed in 12 of 13 operated in our center and the most common contaminants were Neisseria spp and Streptococcus viridians. CONCLUSION: Both anti-TNF and pamidronate appeared superior to NSAIDs alone in treating mandibular CNO. Patients receiving pamidronate responded faster than those receiving anti-TNF therapy.


Assuntos
Doenças Mandibulares/tratamento farmacológico , Osteomielite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças Mandibulares/diagnóstico , Doenças Mandibulares/diagnóstico por imagem , Doenças Mandibulares/patologia , Osteomielite/diagnóstico , Osteomielite/diagnóstico por imagem , Osteomielite/patologia , Pamidronato/uso terapêutico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
20.
BMJ Case Rep ; 12(1)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30674496

RESUMO

This is a case of a 67-year-old woman, known to have multiple medical problems, mainly papillary thyroid cancer status post-total thyroidectomy and cervical neck dissection in addition to radioactive iodine currently in remission for 1 year, who presented to the hospital with severe weakness and fatigue. The initial workup showed significant hypercalcaemia and suppressed Parathyroid hormone (PTH). The patient was treated with hydration and pamidronate and her hypercalcaemia and symptoms improved. The differential was wide, however, a CT scan of the chest, abdomen and pelvis did show multiple liver and splenic nodular lesions; therefore, malignancy was the highest possible diagnosis. Biopsy of the splenic lesion confirmed the diagnosis of sarcoidosis. Therefore, the patient was diagnosed with primary isolated nodular hepatosplenic sarcoidosis mimicking malignancy and causing significant symptomatic hypercalcaemia.


Assuntos
Hipercalcemia/etiologia , Neoplasias/diagnóstico por imagem , Sarcoidose/complicações , Assistência ao Convalescente , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/tratamento farmacológico , Hepatopatias/complicações , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Pamidronato/administração & dosagem , Pamidronato/uso terapêutico , Sarcoidose/diagnóstico por imagem , Sarcoidose/patologia , Sarcoidose/terapia , Esplenopatias/complicações , Esplenopatias/diagnóstico por imagem , Esplenopatias/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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