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1.
Int. j. morphol ; 38(3): 683-688, June 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1098307

RESUMO

The aim was to evaluate bone repair and gingival tissue repair in osteopenic rats. Fifteen female wistar rats were included; in all of them ovariectomy was realized to induce osteopenia; after 45 days, the animals were submitted to 2 surgical techinques 1) dental extraction of the upper central incisor with no socket preservation and 2) 5 mm cranial defect in the calvarium; 5 rats were included in the control group (G1) withput alendronate application; in the group 2 (G2) was used subcutenous alendronate (0.5 mg/kg) once for three weeks and then was realizd the both surgical techniques. In group 3 (G3), after ovariectomy was realized the both dental extraction and the calvarium defect and after that was realized the alendronate protocol. In each group, after six week was realized euthanasia and descriptive histological analysis of the surgical areas involved. In bone formation of the 5 mm cranial defect was observed with good progression in the 3 experimental models and no modification in quality of bone repair was observed. For the gingival tissue in the extraction socket, no differences were observed between G1 and G3. On other hand, in G2 a thinner and reduced gingival epithelium was found. Our results showed that alendronate was not an obstacle for bone repair; deficiencies in re-epithelialization of oral mucosa show the impact of alendronate before dental extraction.


El objetivo fue evaluar la reparación ósea y gingival en ratas con osteopenia. Quince ratas wistar hembras fueron incluidas; en todas ellas se realizo ovarectomia y fue realizada la inducción de osteopenia; después de 45 días, los animales fueron sometidos a dos técnicas quirúrgicas 1) extracciones dentales del incisivo central superior sin preservación alveolar y 2) creación de un defecto craneano de 5 mm en la calota; 5 animales fueron incluidos como grupo control (G1) sin la aplicación de alendronato; en el grupo 2 (G2) se utilizó alendronato subcutáneo (0,5 mg/kg) una vez a la semana durante 3 semanas. En el grupo 3 (G3), después de la ovarectomia se realizó la exodoncia y el defecto en el cráneo y después de ello se inicio el protocolo con alendronato. En cada grupo, después de seis semanas se realizó la eutanasia con descripción histológica de los hallazgos. En el hueso formado en el defecto craneano de 5 mm se observó una adecuada progresión de reparación en los 3 modelos experimentales y no se observó cambios importantes en el modelo de reparación. Para el tejido gingival en el sitio de extracción, no se observaron diferencias entre el grupo G1 y G3. Por otra parte, el G2 presentó un tejido mas delgado con reducción del epitelio gingival; nuestros resultados demuestran que el alendronato no fue un obstáculo en la reparación ósea; deficiencias en la re epitelización de la mucosa oral muestran el impacto del alendronato después de la exodoncia.


Assuntos
Animais , Feminino , Ratos , Doenças Ósseas Metabólicas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Alendronato/administração & dosagem , Gengiva/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Osteoporose/tratamento farmacológico , Doenças Ósseas Metabólicas/complicações , Ovariectomia , Ratos Wistar , Difosfonatos/administração & dosagem
2.
Med. clín (Ed. impr.) ; 154(12): 512-518, jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-195679

RESUMO

INTRODUCCIÓN: La osteogénesis imperfecta (OI) es una enfermedad genética heterogénea manifestada como fragilidad ósea y fracturas. PACIENTES Y MÉTODOS: Estudio descriptivo retrospectivo analizando características clínicas, genéticas y tratamiento de pacientes diagnosticados de OI (1989-2017) en el Hospital Universitario Miguel Servet, Zaragoza (Endocrinología Pediátrica y Reumatología). RESULTADOS: Incluidos 40 pacientes; 32,5% varones, 67,5% mujeres; 29 niños, 11 adultos. Media de fracturas al diagnóstico en OI leve 4,6±6,4 (edad media al diagnóstico 7,8±12,8años), en OI moderada 1,7±2,4 (edad media al diagnóstico 0,04±0,3años), en OI grave 3,7±2,1 y en OI muy grave 12,5±7,8, ambos grupos diagnosticados al nacimiento. Estudio genético en 32 pacientes, 25 con variante patogénica/probablemente patogénica, siendo COL1A1 el gen más frecuentemente afectado. En 7 pacientes no fue encontrada la variante responsable, 5 con confirmación diagnóstica (estudio bioquímico colágenoI). Tratamiento con bifosfonatos 19 pacientes; 7 asociando hormona de crecimiento. Los tratados con bifosfonatos han presentado mejoría clínica (reducción de dolor óseo y/o irritabilidad) y reducción del número de fracturas. CONCLUSIONES: El gen COL1A1 es el más frecuentemente afectado en nuestros pacientes. El tratamiento debe ser multidisciplinar y el uso de bifosfonatos proporciona mejoría


INTRODUCTION: Osteogenesis imperfecta (OI) is a heterogeneous genetic disease manifesting as bone fragility and fractures. PATIENTS AND METHODS: Retrospective descriptive study analysing clinical and genetic features, and treatment of patients with OI. RESULTS: Forty patients were included; 32.5% males, 67.5% females; 29 children, 11 adults. Number of fractures at diagnosis with mild OI was 4.6±6.4 (average age at diagnosis 7.8±12.8years), with moderate OI 1.7±2.4 (age at diagnosis .04±.3years), in severe OI 3.7±2.1 and in extremely severe forms 12.5±7.8, both groups diagnosed at birth. Genetic study in 32 patients, 25 with a positive genetic study (pathogenic/probably pathogenic variant). COL1A1 gene was the most frequently affected. In 7 patients, no pathogenic or probably pathogenic variant was found (5 diagnosed by biochemical study of typeI collagen). Nineteen patients were treated with bisphosphonates; 7 combined with growth hormone. The patients treated with bisphosphonates showed clinical improvement (reduction of bone pain and/or irritability) and reduction of fractures. CONCLUSIONS: The COL1A1 gene is the most frequently affected. OI patients should receive multidisciplinary management and bisphosphonates can improve their quality of life


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Adulto , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/genética , Difosfonatos/administração & dosagem , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/complicações , Estudos Retrospectivos , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/tratamento farmacológico
3.
Orv Hetil ; 161(21): 867-872, 2020 05.
Artigo em Húngaro | MEDLINE | ID: mdl-32427571

RESUMO

INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaw is a condition that severely affects the quality of life, therefore an early diagnosis is of utmost importance (both from a general and a surgical point of view), alongside with an accurate assessment of the risk of emergence of the disease. AIM: Estimation of the prognosis is not resolved; among several radiological options those used in dentistry seem the most fit for the purpose, with cone-beam computed tomography (CBCT) being superior in this task. Assessment of the risk of BRONJ developed following orally applied bisphosphonate is unemphatic in most case studies - these focus more on the intravenous application carrying a greater risk of BRONJ. METHOD: In contrast with the studies published so far, we performed our measurements on preoperative CBCT scans, thereby directly studying the possibility of risk assessment. Our measurements were conducted through evaluating CBCT scans. We chose the frontal section in the midline of the mental foramen as the representative area. We measured density and thickness of the cortical bone on several given points; the diameter of the mental foramen was also measured. In the first group, we examined patients suffering from osteoporosis who had developed BRONJ following oral bisphosphonate treatment. In the second group, we looked at patients suffering from osteoporosis, who had received oral bisphosphonate therapy for this condition but did not develop BRONJ after oral surgery. As control group, we chose patients suffering from osteoporosis who had not received any of the medications known to cause BRONJ. RESULTS: Based on our results, it is clear that there is no significant difference in the bone density of those patients who developed BRONJ and those who did not, examining the preoperative CBCT scans. CONCLUSIONS: Using CBCT scans (and thereby submitting the patient to radiation exposure) in order to estimate the possibility of BRONJ following oral bisphosphonate treatment for osteoporosis is not recommended. It is important not to expose patients to more radiation than strictly necessary to predict BRONJ following oral bisphosphonate treatment in accordance with the ALARA (as low as reasonably achievable) principle. Orv Hetil. 2020; 161(21): 867-872.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Conservadores da Densidade Óssea/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Difosfonatos/efeitos adversos , Medição de Risco/métodos , Tomografia Computadorizada de Feixe Cônico Espiral , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/psicologia , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/administração & dosagem , Humanos , Qualidade de Vida
4.
Ann R Coll Surg Engl ; 102(5): 363-368, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32233846

RESUMO

INTRODUCTION: Hypercalcaemic crisis is a rare manifestation of hyperparathyroidism and occurs in 1.6-6% of patients with primary hyperparathyroidism (pHPT). Although such high serum calcium levels (>14mg/dl) are attributed to malignancy, it is also associated with benign disease of the parathyroid glands. The aim of this study was to evaluate the clinical features and treatment modalities of patients with severe hypercalcaemia who underwent surgery for pHPT. METHODS: The medical records of 537 patients who underwent parathyroidectomy in our department for pHPT between 2005 and 2019 were reviewed retrospectively. Twenty-four (4.4%) of the patients were described as having severe hypercalcaemia. RESULTS: Among 24 patients, 71% were female and the mean age was 55.7 years (range: 40-71 years). The mean serum calcium level at time of diagnosis was 15.9mg/dl (range: 14-22.7mg/dl). According to postoperative pathology reports, solitary adenoma, parathyroid cancer and parathyromatosis were diagnosed with the rates of 87.5%, 8.3% and 4.1% respectively. The mean weight of the solitary parathyroid lesions was 14.9g (standard deviation: 8.9g, range: 4-38g). The mean longest diameter was 2.87cm (standard deviation: 1.4cm, range: 1-5.5cm). Serum calcium levels were within the normal range on the first postoperative day in 75% of the cases. CONCLUSIONS: Severe hypercalcaemia is a rare but urgent condition of pHPT and requires prompt management. Accelerated surgery after adequate medical treatment should be performed. It is important to emphasise that giant adenoma, which is a benign disease, may be a more common cause of severe hypercalcaemia than carcinoma, unlike previously thought.


Assuntos
Adenoma/complicações , Carcinoma/complicações , Hipercalcemia/etiologia , Hiperparatireoidismo Primário/etiologia , Neoplasias das Paratireoides/complicações , Adenoma/sangue , Adenoma/cirurgia , Adulto , Idoso , Cálcio/sangue , Carcinoma/sangue , Carcinoma/cirurgia , Difosfonatos/administração & dosagem , Feminino , Furosemida/administração & dosagem , Humanos , Hipercalcemia/sangue , Hipercalcemia/diagnóstico , Hipercalcemia/terapia , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Neoplasias das Paratireoides/sangue , Paratireoidectomia , Período Pós-Operatório , Diálise Renal , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Sci Rep ; 10(1): 5889, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32246003

RESUMO

Platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks. Herein, we aimed to design radioactive bisphosphonate-functionalized platinum (195mPt-BP) complexes to confirm preferential accumulation of these Pt-based drugs in metabolically active bone. In vitro NMR studies revealed that release of Pt from Pt BP complexes increased with decreasing pH. Upon systemic administration to mice, Pt-BP exhibited a 4.5-fold higher affinity to bone compared to platinum complexes lacking the bone-seeking bisphosphonate moiety. These Pt-BP complexes formed less Pt-DNA adducts compared to bisphosphonate-free platinum complexes, indicating that in vivo release of Pt from Pt-BP complexes proceeded relatively slow. Subsequently, radioactive 195mPt-BP complexes were synthesized using 195mPt(NO3)2(en) as precursor and injected intravenously into mice. Specific accumulation of 195mPt-BP was observed at skeletal sites with high metabolic activity using micro-SPECT/CT imaging. Furthermore, laser ablation-ICP-MS imaging of proximal tibia sections confirmed that 195mPt BP co-localized with calcium in the trabeculae of mice tibia.


Assuntos
Antineoplásicos/administração & dosagem , Osso e Ossos/metabolismo , Difosfonatos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Compostos de Platina/administração & dosagem , Animais , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Osso e Ossos/efeitos dos fármacos , Difosfonatos/uso terapêutico , Injeções Intravenosas , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos de Platina/uso terapêutico , Radioisótopos , Tíbia/metabolismo , Peixe-Zebra
6.
Reumatol. clín. (Barc.) ; 16(2,pt.2): 165-168, mar.-abr. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-194341

RESUMO

La osteogénesis imperfecta (OI) es un trastorno hereditario del tejido conectivo generalmente relacionado con mutaciones de los genes del colágeno tipoI. El diagnóstico se basa en los hallazgos clínicos y radiológicos. El manejo clínico de la OI en adultos no está del todo establecido y comprende desde la rehabilitación física y los procedimientos quirúrgicos hasta el uso de tratamientos antirresortivos y osteoformadores. El objetivo del presente trabajo ha sido analizar las características clínicas y analíticas de estos pacientes en la edad adulta, así como evaluar los diferentes tratamientos administrados. Se han revisado los casos de OI diagnosticados en nuestro centro en los últimos 12 años (2005-2017). Se describen 15 pacientes adultos con OI


Osteogenesis imperfecta (OI) is an inherited connective tissue disease. The disease has been linked to mutations in one of the type I collagen genes. The diagnosis is based on clinical and radiologic findings. The management of OI in adults is not well-established and includes physical rehabilitation, surgical procedures, the use of antiresorptive therapy and anabolic agents. The aim of the present work was to analyze the clinical and analytical characteristics of these patients in adulthood, as well as to evaluate the different treatments administered. We reviewed the cases of OI diagnosed in our center over the last 12 years (2005-2017). We describe 15 adult patients with OI


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/tratamento farmacológico , Difosfonatos/administração & dosagem , Densitometria/métodos , Osteogênese Imperfeita/fisiopatologia , Pró-Colágeno/uso terapêutico , Estudos Retrospectivos , Esclerose/complicações , Dentinogênese , Osteoporose/complicações , Doenças Ósseas Metabólicas/complicações
8.
J Oncol Pharm Pract ; 26(5): 1180-1189, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32122232

RESUMO

While bone-modifying agents such as bisphosphonates and denosumab are crucial to preventing skeletal-related events in patients with bone metastases, the optimal duration remains undefined. Extended duration may be associated with adverse effects such as osteonecrosis of the jaw and atypical femoral fracture. Although uncommon, atypical femoral fracture represents a serious consequence of prolonged bone-modifying agent use and are characterized by a prodrome and distinct radiographic findings. The oncology setting encompasses a unique set of atypical femoral fracture risk factors and considerations, with hormonal therapy in early stage disease, bone metastases in the advanced setting, and new targeted agents that may affect bone homeostasis. As outcomes in cancer treatment continue to improve, the questions of risks versus benefits of long-term bone-modifying agents and how to mitigate atypical femoral fracture risk become increasingly pertinent.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/administração & dosagem , Fraturas do Fêmur/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Denosumab/administração & dosagem , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Humanos , Osteonecrose/induzido quimicamente , Osteonecrose/prevenção & controle , Fatores de Risco
9.
J Manag Care Spec Pharm ; 26(2): 197-202, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32011964

RESUMO

BACKGROUND: Few studies have examined factors that determine bisphosphonate (BP) continuation beyond 5 years in clinical practice. OBJECTIVE: To investigate factors associated with BP continuation among women who completed 5 years of BP therapy. METHODS: Women who received 5 consecutive years of oral BP treatment entered the cohort during 2002-2014 and were followed up to 5 additional years. Multivariable logistic regression was used to evaluate the association of demographic and clinical factors with adherent treatment continuation. RESULTS: The cohort included 19,091 women with a median age of 72 years. Baseline and time-varying factors associated with increased odds of BP continuation after 5 years were (a) most recent bone mineral density (BMD) T-score -2 to -2.4 (OR = 1.31, 95% CI = 1.25-1.38), T-score -2.5 to -2.9 (OR = 1.48, 95% CI = 1.39-1.57), and T-score ≤ -3.0 (OR = 1.57, 95% CI = 1.47-1.68) versus T-scores above -2.0; (b) index date before 2008 (OR =1.35, 95% CI = 1.29-1.41); and (c) diabetes mellitus (OR = 1.08, 95% CI = 1.01-1.16). In contrast, factors associated with decreased odds of BP continuation were (a) recent hip (OR = 0.61, 95% CI = 0.52-0.71) or humerus (OR = 0.79, 95% CI = 0.66-0.94) fracture or fracture other than hip, wrist, spine, or humerus (OR = 0.90, 95% CI = 0.84-0.97); (b) Charlson Comorbidity Index score > 2 (OR = 0.91, 95% CI = 0.84-0.98); (c) history of rheumatoid arthritis (OR = 0.89, 95% CI = 0.80-0.99); (d) Hispanic (OR = 0.89, 95% CI=0.85-0.94) or Asian (OR = 0.90, 95% CI = 0.85-0.94) race/ethnicity; and (e) use of proton pump inhibitors (OR = 0.65, 95% CI = 0.59-0.71). Patient age and fracture before BP initiation were not associated with treatment continuation. CONCLUSIONS: Clinical factors predicting continued BP treatment beyond 5 years include low BMD T-score, absence of recent fracture, and earlier era of treatment. Use of proton pump inhibitors was associated with lower likelihood of BP continuation. Other clinical and demographic factors were also noted to have variable effects on BP treatment continuation. DISCLOSURES: This study was supported by a grant from the National Institute on Aging and National Institute of Arthritis, Musculoskeletal and Skin Diseases at the National Institutes of Health (NIH; R01AG047230, S1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Kaiser Permanente. Lo has received previous research funding from Amgen and Sanofi, unrelated to the current study. Adams has received previous research funding from Merck, Amgen, Otsuka, and Radius Health, unrelated to the current study. Ettinger has served as an expert witness for Teva Pharmaceuticals, unrelated to the current study. Ott previously attended a scientific advisory meeting for Amgen but declined the honorarium. The other authors have nothing to disclose. These data were presented at the 2018 Annual Meeting of the American Society of Bone and Mineral Research (ASBMR), September 28-October 1, 2018, Montreal, Quebec, Canada.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/complicações , Fraturas por Osteoporose/epidemiologia , Inibidores da Bomba de Prótons/administração & dosagem , Fatores de Tempo
10.
Niger J Clin Pract ; 23(2): 154-158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32031088

RESUMO

Background: There are a lot study confirmed the relationship of bone serum markers changes and skeletal irregularities. But there is no sufficient case control studies about the role of these markers on bisphosphonate induced osteonecrosis of jaws (BRONJ). Aims: The aim of this study is to find out if there is any derangement of bone markers in bisphosphonate-treated patients with ONJ. Methods: We obtained serum bone markers and other relevant endocrine assays on 20 patients with osteonecrosis of the jaw (ONJ) and 20 randomized healthy volunteers. All of the ONJ group treated with zoledronic acid and had been withdrawn from bisphosphonate for at least 6 months. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. The biochemical assays were performed on N-Telopeptides of type I collagen (NTX), bone-specific alkaline phosphatase (ALP), calcitonin, osteocalcin, intact parathyroid hormone (PTH), T3, T4, TSH, and Vitamin D 25 hydroxy (Vit-D). Results: In ONJ group, PTH level is statistically higher and TSH, Vit-D, osteocalcin and NTX levels statistically lower compared to control group. Conclusion: We conclude that these changes in PTH, Vit-D, TSH, osteocalcin and NTX levels maybe have a role in the pathophysiology of BRONJ. But the data need to be confirmed by future studies.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/sangue , Conservadores da Densidade Óssea/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Colágeno Tipo I/sangue , Difosfonatos/efeitos adversos , Hormônio Paratireóideo/sangue , Vitamina D/sangue , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Conservadores da Densidade Óssea/administração & dosagem , Estudos de Casos e Controles , Difosfonatos/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina , Peptídeos , Ácido Zoledrônico/uso terapêutico
11.
Support Care Cancer ; 28(11): 5223-5233, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32086567

RESUMO

PURPOSE: Bisphosphonates and denosumab prevent bone complications in patients with bone metastases from solid tumours. This retrospective, longitudinal, cohort study provides data on their real-world use in this setting in Germany. METHODS: Adults with bone metastases from breast, prostate or lung cancer who were newly initiated on a bisphosphonate or denosumab between 1 July 2011 and 31 December 2015 were identified from a German healthcare insurance claims database. Primary outcomes included persistence, compliance, discontinuation and switch rates at 12 months. RESULTS: This study included 1130 patients with bone metastases: 555 (49%) had breast cancer, 361 (32%) prostate cancer and 242 (21%) lung cancer. Mean age was 65 years for patients with breast or lung cancer and 74 years for those with prostate cancer. Across all tumour types, compared with any bisphosphonate, 12-month persistence was higher with denosumab (breast cancer 78% vs 54-58%, prostate cancer 58% vs 50%, lung cancer 68% vs 34-60%), median time to discontinuation was longer with denosumab and switch rates were lower for denosumab (breast cancer 5% vs 14-19%, prostate cancer 2% vs 11%, lung cancer 3% vs 7-12%). Compliance at 12 months was longer for denosumab than for any bisphosphonate in breast cancer (75% vs 42-48%) and in prostate cancer (47% vs 36%). CONCLUSIONS: Patients initiated on denosumab following a diagnosis of bone metastases from breast, prostate or lung cancer had greater medication persistence, longer time to discontinuation, improved compliance and lower switch rates than those initiated on a bisphosphonate.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Denosumab/administração & dosagem , Difosfonatos/administração & dosagem , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Alemanha , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Adesão à Medicação , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Estudos Retrospectivos
12.
Support Care Cancer ; 28(6): 2533-2540, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32060705

RESUMO

BACKGROUND: Bisphosphonates are wildly used in breast cancer patients with bone metastasis and generally administrated every 4 weeks to lessen the risk of subsequent skeletal-related events. Bisphosphonates administration every 12 weeks is also recommended in some guidelines. Recent clinical trials suggested that bisphosphonate treatment with reduced frequency (every 12 weeks) to be non-inferior to standard therapy. The object of this analysis was to contrast the efficacy and safety of these two treatment strategies. METHOD: We systematically retrieved databases such as MEDLINE, PubMed, Embase, and Cochrane library from 1947 to present for clinical trials comparing the efficacy between standard (every 4 weeks) and de-escalation (every 12 weeks) treatment of bisphosphates. RESULTS: We identified 4 articles with available data from 4 randomized clinical trials (n = 1721). Administration of bisphosphate every 12 weeks was non-inferior to administration every 4 weeks. There existed no significant difference in on-study skeletal-related events, renal dysfunction, and osteonecrosis of jaw. In the exploratory study, patients who received intravenous bisphosphates before enrollment experienced less on-study skeletal-related events and significant difference was observed between groups. CONCLUSION: This analysis suggested that de-escalation treatment with bisphosphates may be superior to standard treatment in terms of efficacy, safety, and economic costs. But it would be better that all the patients receive bisphosphates every 4 weeks for several months before de-escalation.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Difosfonatos/administração & dosagem , Feminino , Humanos , Padrão de Cuidado
14.
Med Care ; 58(5): 419-426, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31985584

RESUMO

BACKGROUND: Discontinuation of bisphosphonates (BP) or a "drug holiday" after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. OBJECTIVES: We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. RESEARCH DESIGN: Observational cohort study using US Medicare data 2006-2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. SUBJECTS: Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥80%) to alendronate, risedronate, or zoledronate for ≥3 years. MEASURES: Hip, humerus, distal forearm, and clinical vertebral fracture. RESULTS: Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for >2 years was 13.2 per 1000 person-years. Risk was increased (aHR=1.3, 1.1-1.4) versus continuing therapy (IR=8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR=1.3, 1.1-1.66) and for clinical vertebral fracture with discontinuation >2 years (aHR=1.2, 1.1-1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. CONCLUSION: Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Fraturas do Quadril/epidemiologia , Fraturas do Úmero/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Estudos de Coortes , Difosfonatos/efeitos adversos , Esquema de Medicação , Feminino , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/prevenção & controle , Humanos , Medicare , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Fatores de Tempo , Estados Unidos/epidemiologia , Suspensão de Tratamento
15.
J Womens Health (Larchmt) ; 29(2): 177-186, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31895627

RESUMO

Background: Recommendations for using menopausal hormone therapy (MHT) and bisphosphonates for postmenopausal osteoporosis management have changed over time. After the release of the Women's Health Initiative (WHI) trial results in 2002, new evidence on risks and benefits of MHT became available, and newer guidelines generally specify that MHT should not be prescribed for prevention of chronic disease, including osteoporosis. This raises the question of whether bisphosphonate prescribing changed over time to compensate for the decrease in MHT use. Materials and Methods: We examined trends in dispensed prescriptions in Australia (national) and Canada (province of Manitoba) in relation to prescribing recommendations. Administrative data were used to describe dispensing patterns and changes for persons of all ages from 1996 to 2008, and for women aged 50 to ≥80 years from 2003 to 2008 in Australia and 1996 to 2008 in Canada. Results: In both geographic settings, MHT dispensing increased 1996-2001, peaked in 2001, and declined substantially thereafter (67% reduction in MHT prescriptions for Australia; 64% reduction for Manitoba, Canada to 2008). From 2003 to 2008, the number of MHT prescriptions declined among all age groups in both settings, with the highest declines among women in their 50s. Concurrently, bisphosphonate dispensing increased until 2005 (2001-2005: 260% increase in the number of prescriptions in Australia; 125% increase in Manitoba) and stabilized thereafter, in both settings. Annual bisphosphonate dispensing rates increased 4.1-10.9% for women in their 70s and 80s in Australia and Manitoba during the period studied. Conclusions: Based on dispensed prescriptions data, more recent guidelines for MHT and bisphosphonates use for postmenopausal osteoporosis, which were updated during the study period (and are still consistent with the current guidelines), appear to have been broadly adhered to in both settings.


Assuntos
Difosfonatos/administração & dosagem , Terapia de Reposição Hormonal/tendências , Osteoporose Pós-Menopausa/tratamento farmacológico , Padrões de Prática Médica/tendências , Idoso , Austrália , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/uso terapêutico , Estrogênios/administração & dosagem , Feminino , Fidelidade a Diretrizes , Humanos , Manitoba , Pessoa de Meia-Idade , Progestinas/administração & dosagem
16.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634910

RESUMO

CONTEXT: Intravenous aminobisphosphonates (N-BPs) can induce an acute phase reaction (APR) in up to 40% to 70% of first infusions, causing discomfort and often requiring intervention with analgesics or antipyretics. OBJECTIVE: Our aim was to explore the risk factors of APR in a large sample of patients with Paget's disease of bone (PDB) and to assess the possible preventive effects of vitamin D administration. METHODS: An observational analysis was performed in 330 patients with PDB at the time of N-BP infusion. Then, an interventional study was performed in 66 patients with active, untreated PDB to evaluate if vitamin D administration (oral cholecalciferol 50 000 IU/weekly for 8 weeks before infusion) may prevent APR. RESULTS: In a retrospective study, APR occurred in 47.6% and 18.3% of naive or previously treated patients, respectively. Its prevalence progressively increased in relation to the severity of vitamin D deficiency, reaching 80.0% in patients with 25-hydroxyvitamin D (25OHD) levels below 10 ng/mL (relative risk (RR) = 3.7; 95% confidence interval (CI) 2.8-4.7, P < .0001), even in cases previously treated with N-BPs. Moreover, APR occurred more frequently in patients who experienced a previous APR (RR = 2.8; 95% CI 1.5-5.2; P < .001) or in carriers of SQSTM1 mutation (RR = 2.3; 95% CI 1.3-4.2; P = .005). In the interventional study, vitamin D supplementation prevented APR in most cases, equivalent to a RR of 0.31 (95% CI 0.14-0.67; P < .005) with respect to prevalence rates of the observational cohort. A similar trend was observed concerning the occurrence of hypocalcemia. CONCLUSIONS: The achievement of adequate 25OHD levels is recommended before N-BP infusion in order to minimize the risk of APR or hypocalcemia in PDB.


Assuntos
Reação de Fase Aguda/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Colecalciferol/administração & dosagem , Difosfonatos/efeitos adversos , Osteíte Deformante/tratamento farmacológico , Deficiência de Vitamina D/dietoterapia , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/epidemiologia , Reação de Fase Aguda/imunologia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/administração & dosagem , Suplementos Nutricionais , Difosfonatos/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/sangue , Osteíte Deformante/complicações , Prevalência , Estudos Retrospectivos , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/imunologia
17.
Surgery ; 167(1): 144-148, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31582307

RESUMO

BACKGROUND: Parathyroidectomy (PTX) increases bone mineral density and decreases fracture risk in patients with primary hyperparathyroidism. This study examined the effect of adding bisphosphonates either before or after PTX on skeletal outcomes. METHODS: A retrospective cohort study of bisphosphonate-naïve patients (1995-2016) with osteoporosis and primary hyperparathyroidism (calcium >10.5 mg/dL; PTH >65) was performed. Time-varying Cox regression was used to estimate an adjusted risk of any fracture in 5 comparison groups: observation, bisphosphonates alone, PTX alone, bisphosphonates then PTX, and PTX then bisphosphonates. The secondary outcome was change in bone mineral density of the hip. RESULTS: The cohort comprised 1,737 patients, of whom 303 underwent PTX (17%), 433 received bisphosphonates only (25%), 125 had bisphosphonates then PTX (7%), and 69 had PTX then bisphosphonates (4%). PTX was associated with a decrease in fracture risk (HR 0.55, 95% CI 0.35-0.84), as was bisphosphonates then PTX (HR 0.46, 95% CI 0.25-0.83). In contrast, the fracture risks associated with PTX then bisphosphonates (HR 1.09, 95% CI 0.65-1.81) and bisphosphonates alone (HR 0.82, 95% CI 0.62-1.08) were similar to observation. Hip bone mineral density increased after both PTX (5.50%, 95% CI 3.39-7.61) and PTX then bisphosphonates (6.30%, 95% CI 2.53-10.07). CONCLUSION: Bisphosphonate initiation after PTX may interfere with the beneficial effects of PTX on fracture risk in osteoporotic patients with primary hyperparathyroidism.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Hiperparatireoidismo Primário/terapia , Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Paratireoidectomia , Absorciometria de Fóton , Idoso , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Terapia Combinada/métodos , Difosfonatos/administração & dosagem , Feminino , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/complicações , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/prevenção & controle , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Hormônio Paratireóideo/sangue , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
18.
J Clin Pharm Ther ; 45(1): 45-51, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31608489

RESUMO

WHAT IS KNOWN AND OBJECTIVE: There have been concerns about a potential link between long-term use of bisphosphonates (BPs) for the treatment of osteoporosis and rare serious adverse effects, such as atypical femoral fractures. However, many reviews exist with conflicting conclusions about this issue. The aim of this overview of reviews was to systematically evaluate the risk of rare serious adverse effects of long-term use of BPs for the treatment of osteoporosis. METHODS: We identified systematic reviews with meta-analyses of randomized controlled trials (RCTs) and (or) observational studies published in English or Chinese that evaluated the safety of BPs through to December 2018. The Cochrane library, PubMed, Web of Science and hand-searching of reference lists and clinical practice guidelines were electronically searched for data sources. Carcinogenicity, atypical fracture, osteonecrosis of jaw (ONJ) and fracture union time were specified as the primary outcomes. The methodological quality of each systematic review was assessed by two reviewers using the Assessment of Multiple Systematic Reviews (AMSTAR) tool, and the quality of evidence for key outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS AND DISCUSSION: In total, 1376 potentially relevant citations were identified, of which only 8 systematic reviews with meta-analyses met the eligibility criteria. All the included reviews were published between 2012 and 2015 and documented the pooled estimates of effect size (relative risk [RR], odds ratio [OR] or hazard ratio [HR] and their 95% confidence intervals [95% CI]) for the incidence of adverse events. All included systematic reviews were of moderate or high quality. The median AMSTAR score was 7.5 (interquartile range, 5-10). However, evidence of the key outcomes was mainly of very low or moderate quality. BP treatment only increased the risk of atypical fracture and ONJ, and prolonged union time compared with placebo or other anti-osteoporosis drugs (P ï¼œ .05). WHAT IS NEW AND CONCLUSION: This study indicated that long-term use of BPs could increase the risk of rare serious adverse effects, but the relationship between long-term use of BPs and carcinogenicity was often uncertain. Therefore, high-quality research and more complete inclusion criteria are needed.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Osteoporose/tratamento farmacológico , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
19.
Am J Epidemiol ; 189(3): 224-234, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31673702

RESUMO

Studies have shown that accounting for time-varying confounding through time-dependent Cox proportional hazards models may provide biased estimates of the causal effect of treatment when the confounder is also a mediator. We explore 2 alternative approaches to addressing this problem while examining the association between vitamin D supplementation initiated after breast cancer diagnosis and all-cause mortality. Women aged 50-80 years were identified in the National Cancer Registry Ireland (n = 5,417) between 2001 and 2011. Vitamin D use was identified from linked prescription data (n = 2,570). We sought to account for the time-varying nature of vitamin D use and time-varying confounding by bisphosphonate use using 1) marginal structural models (MSMs) and 2) G-estimation of structural nested accelerated failure-time models (SNAFTMs). Using standard adjusted Cox proportional hazards models, we found a reduction in all-cause mortality in de novo vitamin D users compared with nonusers (hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.73, 0.99). Additional adjustment for vitamin D and bisphosphonate use in the previous month reduced the hazard ratio (HR = 0.45, 95% CI: 0.33, 0.63). Results derived from MSMs (HR = 0.44, 95% CI: 0.32, 0.61) and SNAFTMs (HR = 0.45, 95% CI: 0.34, 0.52) were similar. Utilizing MSMs and SNAFTMs to account for time-varying bisphosphonate use did not alter conclusions in this example.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Modelos Estatísticos , Sistema de Registros , Vitamina D/uso terapêutico , Idoso , Neoplasias da Mama/mortalidade , Fatores de Confusão Epidemiológicos , Difosfonatos/administração & dosagem , Feminino , Humanos , Irlanda/epidemiologia , Pessoa de Meia-Idade , Fatores de Tempo
20.
Eur J Epidemiol ; 35(1): 37-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734885

RESUMO

The use of bisphosphonates has been associated with a decrease in the risk of colorectal cancer (CRC) in observational studies, but with controversial results and difficult to interpret because of routine concomitant use of calcium and vitamin D. We aimed to assess the association between CRC risk and outpatient exposure to antiosteoporotic drugs using a large cohort with prescription data in Catalonia. A case-control study was performed using the Information System for Development of Primary Care Research (SIDIAP) which is a primary care medical record database that has linked data on reimbursed medication. The study included 25,836 cases with an incident diagnosis of CRC between 2010 and 2015 and 129,117 matched controls by age (± 5 years), sex and healthcare region. A multivariable model was built adjusting for known risk factors and comorbidities that were significantly associated to CRC in the dataset, and a propensity score for bisphosphonates. Tests for interaction for multiple drug use and stratified analysis for tumour location were prospectively planned. Overall 18,230 individuals (11.5%) were users of bisphosphonates. A significant but modest protective effect on CRC was observed for bisphosphonates (OR 0.95, 95% CI 0.91-0.99), that was no longer significant when adjusted for calcium and vitamin D (OR 0.98, 95% CI 0.93-1.03). Bisphosphonates, however, showed a dose-response effect with duration of use even when adjusted for calcium and vitamin D (OR for use > 40 months: 0.90, 95% CI 0.81-1.00, P value for trend: 0.018). The use of bisphosphonates was associated with a modest decrease in the risk of CRC, but this effect was essentially explained by concomitant use of calcium or vitamin D. The observed protective effect was stronger for long durations of use, which deserves further study.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Difosfonatos/uso terapêutico , Registros Eletrônicos de Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/administração & dosagem , Estudos de Casos e Controles , Quimioprevenção , Difosfonatos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Adulto Jovem
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