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BACKGROUND: Recent studies have highlighted multicolumn spinal cord stimulation (SCS) efficacy, hypothesizing that optimized spatial neural targeting provided by new-generation SCS lead design or its multicolumn programming abilities could represent an opportunity to better address chronic back pain (BP). OBJECTIVE: To compare multicolumn vs. monocolumn programming on clinical outcomes of refractory postoperative chronic BP patients implanted with SCS using multicolumn surgical lead. MATERIALS AND METHODS: Twelve centers included 115 patients in a multicenter, randomized, double-blind, controlled trial. After randomization, leads were programmed using only one or several columns. The primary outcome was change in BP visual analogic scale (VAS) at six months. All patients were then programmed using the full potential of the lead up until 12-months follow-up. RESULTS: At six months, there was no significant difference in clinical outcomes whether the SCS was programmed using a mono or a multicolumn program. At 12 months, in all patients having been receiving multicolumn SCS for at least six months (n = 97), VAS decreases were significant for global pain (45.1%), leg pain (55.8%), and BP (41.5%) compared with baseline (p < 0.0001). CONCLUSION: The ESTIMET study confirms the significant benefit experienced on chronic BP by patients implanted with multicolumn SCS, independently from multicolumn lead programming. These good clinical outcomes might result from the specific architecture of the multicolumn lead, giving the opportunity to select initially the best column on a multicolumn grid and to optimize neural targeting with low-energy requirements. However, involving more columns than one does not appear necessary, once initial spatial targeting of the "sweet spot" has been achieved. Our findings suggest that this spatial concept could also be transposed to cylindrical leads, which have drastically improved their capability to shape the electrical field, and might be combined with temporal resolution using SCS new modalities.
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Síndrome Pós-Laminectomia , Estimulação da Medula Espinal , Dor nas Costas/terapia , Humanos , Medição da Dor , Estudos Prospectivos , Medula Espinal , Resultado do TratamentoRESUMO
Over the past 50years, increasing experimental evidences have established that connexins (Cxs) and gap junctional intercellular communication (GJIC) ensure an important role in both the onset and development of cancerous processes. In the present review, we focus on the impact of Cxs and GJIC during the development of prostate cancer (PCa), from the primary growth mainly localized in acinar glands and ducts to the distant metastasis mainly concentrated in bone. As observed in several other types of solid tumours, Cxs and especially Cx43 exhibit an ambivalent role with a tumour suppressor effect in the early stages and, conversely, a rather pro-tumoural profile for most of invasion and dissemination steps to secondary sites. We report here the current knowledge on the function of Cxs during PCa cells migration, cytoskeletal dynamics, proteinases activities and the cross talk with the surrounding stromal cells in the microenvironment of the tumour and the bones. In addition, we discuss the role of Cxs in the bone tropism even if the prostate model is rarely used to study the complete sequence of cancer dissemination compared to breast cancer or melanoma. Even if not yet fully understood, these recent findings on Cxs provide new insights into their molecular mechanisms associated with progression and bone targeted behaviour of PCa. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve.
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Conexina 43 , Junções Comunicantes , Proteínas de Neoplasias , Neoplasias da Próstata , Microambiente Tumoral , Animais , Conexina 43/genética , Conexina 43/metabolismo , Junções Comunicantes/genética , Junções Comunicantes/metabolismo , Junções Comunicantes/patologia , Humanos , Masculino , Metástase Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
Hypophosphatasia (HPP) is a rare inherited metabolic bone disease due to a deficiency of the tissue nonspecific alkaline phosphatase isoenzyme (TNSALP) encoded by the ALPL gene. Patients have consistently low serum alkaline phosphatase (AP), so that this parameter is a good hallmark of the disease. Adult HPP is heterogeneous, and some patients present only mild nonpathognomonic symptoms which are also common in the general population such as joint pain, osteomalacia and osteopenia, chondrocalcinosis, arthropathy and musculoskeletal pain. Adult HPP may be recessively or dominantly inherited; the latter case is assumed to be due to the dominant negative effect (DNE) of missense mutations derived from the functional homodimeric structure of TNSALP. However, there is no biological argument excluding the possibility of other causes of dominant HPP. Rheumatologists and endocrinologists are increasingly solicited for patients with low AP and nonpathognomonic symptoms of HPP. Many of these patients are heterozygous for an ALPL mutation and a challenging question is to determine if these symptoms, which are also common in the general population, are attributable to their heterozygous ALPL mutation or not. In an attempt to address this question, we reviewed a cohort of 61 adult patients heterozygous for an ALPL mutation. Mutations were distinguished according to their statistical likelihood to show a DNE. One-half of the patients carried mutations predicted with no DNE and were slightly less severely affected by the age of onset, serum AP activity and history of fractures. We hypothesized that these mutations result in another mechanism of dominance or are recessive alleles. To identify other genetic factors that could trigger the disease phenotype in heterozygotes for potential recessive mutations, we examined the next-generation sequencing results of 32 of these patients for a panel of 12 genes involved in the differential diagnosis of HPP or candidate modifier genes of HPP. The heterozygous genotype G/C of the COL1A2 coding SNP rs42524 c.1645C > G (p.Pro549Ala) was associated with the severity of the phenotype in patients carrying mutations with a DNE whereas the homozygous genotype G/G was over-represented in patients carrying mutations without a DNE, suggesting a possible role of this variant in the disease phenotype. These preliminary results support COL1A2 as a modifier gene of HPP and suggest that a significant proportion of adult heterozygotes for ALPL mutations may have unspecific symptoms not attributable to their heterozygosity.
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Fosfatase Alcalina/genética , Predisposição Genética para Doença , Mutação/genética , Adolescente , Adulto , Idoso , Fosfatase Alcalina/sangue , Feminino , Genes Dominantes , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Adulto JovemRESUMO
Hypophosphatasia (HPP) is a rare inherited skeletal dysplasia due to loss of function mutations in the ALPL gene. The disease is subject to an extremely high clinical heterogeneity ranging from a perinatal lethal form to odontohypophosphatasia affecting only teeth. Up to now genetic diagnosis of HPP is performed by sequencing the ALPL gene by Sanger methodology. Osteogenesis imperfecta (OI) and campomelic dysplasia (CD) are the main differential diagnoses of severe HPP, so that in case of negative result for ALPL mutations, OI and CD genes had often to be analyzed, lengthening the time before diagnosis. We report here our 18-month experience in testing 46 patients for HPP and differential diagnosis by targeted NGS and show that this strategy is efficient and useful. We used an array including ALPL gene, genes of differential diagnosis COL1A1 and COL1A2 that represent 90% of OI cases, SOX9, responsible for CD, and 8 potentially modifier genes of HPP. Seventeen patients were found to carry a mutation in one of these genes. Among them, only 10 out of 15 cases referred for HPP carried a mutation in ALPL and 5 carried a mutation in COL1A1 or COL1A2. Interestingly, three of these patients were adults with fractures and/or low BMD. Our results indicate that HPP and OI may be easily misdiagnosed in the prenatal stage but also in adults with mild symptoms for these diseases.
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Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Adulto , Idoso , Displasia Campomélica/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Feminino , Feto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipofosfatasia/fisiopatologia , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Osteogênese Imperfeita/diagnóstico , Desmineralização do Dente/congênito , Desmineralização do Dente/fisiopatologiaRESUMO
INTRODUCTION: Hypophosphatasia (HPP) is a rare genetic disease caused by loss-of-function mutations in the ALPL gene encoding the tissue non-specific alkaline phosphatase (ALP). Mild HPP is usually misdiagnosed in adult age. While an elevated serum ALP value draws more attention than a low value, low serum ALP should be better recognised and may lead to HPP detection. METHODS: Patients were selected from the records of the biochemistry department of six University Hospitals in France. Patients were hospitalised in the departments of rheumatology and internal medicine between 2007 and 2017. RESULTS: 56 321 hospitalised patients had at least 2 serum ALP dosages and 664 of these patients had at least 2 low serum ALP≤35 UI/L. Among these 664 patients, 482 (72.6%) had fluctuating low values (mean age 62.9 years; 60% of women) and 182 patients (27.4%) had persistent low values below 35 IU/L (mean age 53.4 years; 67% of women). Among patients with persistent hypophosphatasaemia treated with bisphosphonates, 70.8% never had ALP measurement before treatment and 20.8% were treated despite an abnormal decrease of ALP. Genetic testing was performed in 18 patients and was positive in 11. Genetic diagnosis of HPP was at least 6.0% in persistent hypophosphatasaemia and at least 15.9% in patients with at least three symptoms suggestive of HPP. CONCLUSION: In this 10-year retrospective study, 0.32% of adult patients hospitalised in the rheumatology and internal medicine departments had persistently low serum ALP, and among them, 6% had genetically proven HPP. Reported hypophosphatasaemia represented only 3.6% of hospitalised patients.
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Hipofosfatasia , Reumatologia , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Hipofosfatasia/diagnóstico , Hipofosfatasia/epidemiologia , Hipofosfatasia/genética , Fosfatase Alcalina/genética , Estudos Retrospectivos , MutaçãoRESUMO
BACKGROUND: Pregnancy and breastfeeding are associated with bone density loss. Fracture occurrence during pregnancy and post-partum, and its determinants, remain poorly known in Osteogenesis Imperfecta (OI). The aim of this study was to characterize fractures that occurred during pregnancy and post-partum in OI patients. RESULTS: We conducted a retrospective multicentric study including a total of 50 previously pregnant OI women from 10 Bone Centers in France. Among these patients, 12 (24%) patients experienced fractures during pregnancy or in the 6 months following delivery, and 38 (76%) did not experience any fracture. The most frequent localizations were: proximal femur (25%), spine (25%), distal femur (12.5%), and pelvis (12.5%). Fractures during pregnancy occurred during the third trimester and post-partum fractures occurred with a mean delay of 2 months following delivery. No fractures occurred during childbirth. We next compared the 12 patients with pregnancy or post-partum fractures with the 38 patients without fractures. Mean age at pregnancy was 32.7 ± 3.1 years-old in the fractured group, vs 29.3 ± 5.0 years-old in the non-fractured group (p = 0.002). Breastfeeding was reported in 85.7% of patients in the fractured group, vs 47.1% in the non-fractured group (p = 0.03). All patients with post-partum fractures were breastfeeding. Bone mineral density was significantly lower in patients with pregnancy-related fractures compared with other patients: spine Z-score - 2.9 ± 1.6DS vs - 1.5 ± 1.7DS (p = 0.03), and total hip Z-score - 2.0 ± 0.7DS vs - 0.5 ± 1.4DS (p = 0.04). At least one osteoporosis-inducing risk factor or disease other than OI was identified in 81.8% vs 58.6% of fractured vs non-fractured patients (not significant). Fracture during pregnancy or post-partum was not associated with the severity of OI. Bisphosphonates before pregnancy were reported in 16.7% and 21.1% of patients with pregnancy-related fractures and non-fractured patients, respectively (not significant). CONCLUSIONS: OI management during pregnancy and post-partum should aim for optimal control of modifiable osteoporosis risk factors, particularly in patients with low BMD. Breastfeeding should be avoided.
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Conservadores da Densidade Óssea , Fraturas Ósseas , Osteogênese Imperfeita , Adulto , Densidade Óssea , Difosfonatos , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Osteogênese Imperfeita/epidemiologia , Período Pós-Parto , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The study aimed to describe the characteristics of women treated for recently-diagnosed osteoporosis, to identify variables associated with different treatment regimens and to assess impact on quality of life. METHODS: This is an observational, cross-sectional pharmacoepidemiological study performed in France. A random sample of 684 general practitioners, gynaecologists and rheumatologists included the first three post-menopausal osteoporotic women consulting in the previous six months on the basis of densitometry or fracture. Data on osteoporosis, fracture risk factors, treatments and comorbidities was collected with a physician questionnaire. Data on quality of life was collected using the SF-12. RESULTS: Data were analysed for 1,306 patients, of whom 1,117 (85.5%) had been evaluated by densitometry within the previous six months and 554 (42.4%) had experienced a fracture, most frequently of the spine or wrist within the previous six months. Osteoporotic fracture risk factors were reported in 1,028 women (78.7%). 746 women (57.1%) were currently receiving treatment, most frequently weekly or monthly bisphosphonates. Five variables were associated with prescription choice: age (p < 0.0001), physician speciality (p < 0.0001), previous fracture history (p = 0.0002), ongoing treatment at the time of consultation (p = 0.0091) and paraclinical investigations performed in the previous six months (p = 0.0060). SF-12 scores were lower in women complaining of pain, with recent fractures and with spine or hip fractures and in women consulting rheumatologists. CONCLUSIONS: A high proportion of women diagnosed with osteoporosis had been evaluated by densitometry, in agreement with national guidelines. Treatment choice varied between physician groups.
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Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/psicologia , Qualidade de Vida/psicologia , Idoso , Cadáver , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico por imagem , RadiografiaRESUMO
Bone is a dynamic tissue that undergoes a precise remodeling process involving resorptive osteoclastic cells and bone-forming osteoblastic (OB) cells. The functional imbalance of either of these cell types can lead to severe skeletal diseases. The proliferation and differentiation of OB cells play a major role in bone development and turnover. These cellular processes are coordinated by connexin43 (Cx43)-based gap-junctional intercellular communication (GJIC) and by soluble factors such as endothelin-1 (ET-1). We have used the Cx43 heterozygous (Cx43(+/-)) murine model to study the possible cross-talk between Cx43 and ET-1 in cultured calvarial OB cells. On microcomputed tomographic analysis of 3-day-old pups, Cx43(+/-) mice showed hypomineralized calvaria in comparison with their Cx43(+/+) littermates. Characterization of cultured OB cells clearly demonstrated the effect of the partial deletion of the Cx43 gene on its expression, on GJIC, and subsequently on OB differentiation. In this model, ET-1 (10(-8) M) lost its mitogenic action in Cx43(+/-) OB cells compared with Cx43(+/+) cells. Moreover, a correlation between the inhibition of cell differentiation by ET-1 and the decreased amount and function of Cx43 was found in Cx43(+/+) OB cells but not in their Cx43(+/-) counterparts. Thus, as Cx43 is linked to OB differentiation, our data indicate that this mitogenic ET-1 peptide has pronounced effects on fully differentiated OB cells. With respect to roles in mechanotransduction and OB differentiation, Cx43 might modulate osteoblastic sensitivity to soluble factors.
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Diferenciação Celular/genética , Conexina 43/metabolismo , Endotelina-1/metabolismo , Junções Comunicantes/metabolismo , Osteoblastos/metabolismo , Osteogênese/genética , Animais , Doenças Ósseas Metabólicas/genética , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/genética , Calcificação Fisiológica/genética , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/genética , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/genética , Proliferação de Células , Conexina 43/genética , Endotelina-1/farmacologia , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/genética , Inibidores do Crescimento/metabolismo , Inibidores do Crescimento/farmacologia , Mecanotransdução Celular/efeitos dos fármacos , Mecanotransdução Celular/fisiologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Crânio/diagnóstico por imagem , Crânio/metabolismo , Crânio/fisiopatologia , Microtomografia por Raio-XRESUMO
BACKGROUND: Adherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance. METHODS: This was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis. RESULTS: 785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (κ: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life. CONCLUSION: Compliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance.
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Conservadores da Densidade Óssea/administração & dosagem , Adesão à Medicação , Osteoporose Pós-Menopausa/tratamento farmacológico , Satisfação do Paciente , Idoso , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/psicologia , Osteoporose Pós-Menopausa/terapia , Farmacoepidemiologia , Caminhada/fisiologia , Caminhada/psicologiaRESUMO
Among the different interacting molecules implicated in bone metastases, connexin43 (Cx43) may increase sensitivity of prostate cancer (PCa) cells to bone microenvironment, as suggested by our in silico and human tissue samples analyses that revealed increased level of Cx43 expression with PCa progression and a Cx43 specific expression in bone secondary sites. The goal of the present study was to understand how Cx43 influences PCa cells sensitivity and aggressiveness to bone microenvironment. By means of Cx43-overexpressing PCa cell lines, we revealed a Cx43-dependent promigratory effect of osteoblastic conditioned media (ObCM). This effect on directional migration relied on the presence of Cx43 at the plasma membrane and not on gap junctional intercellular communication and hemichannel functions. ObCM stimulation induced Rac1 activation and Cx43 interaction with cortactin in protrusions of migrating PCa cells. Finally, by transfecting two different truncated forms of Cx43 in LNCaP cells, we determined that the carboxy terminal (CT) part of Cx43 is crucial for the responsiveness of PCa cells to ObCM. Our study demonstrates that Cx43 level and its membrane localization modulate the phenotypic response of PCa cells to osteoblastic microenvironment and that its CT domain plays a pivotal role.
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With intermittent vitamin D supplementation, serum 25-hydroxyvitamin D (25OHD) levels may remain stable only if the dosing interval is shorter than 3 months, the ideal perhaps being about 1 month. Recent data support moderate daily vitamin D doses instead of high intermittent doses, notably in elderly patients prone to falls. The level of evidence is low, however, with no head-to-head comparisons of clinical outcomes such as fractures and falls in groups given identical dosages daily versus intermittently. A challenge to daily vitamin D supplementation in France is the absence of a suitable pharmaceutical formulation. In addition, daily dosing carries a high risk of poor adherence. Until suitable vitamin D3 formulations such as tablets or soft capsules each containing 1000 or 1500 IU become available, we suggest intermittent supplementation according to 2011 GRIO guidelines. Among the available dosages, the lowest should be preferred, with the shortest possible interval, e.g., 50,000 IU monthly rather than 100,000 every two months.
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Osteoporose , Deficiência de Vitamina D , Idoso , Colecalciferol , Suplementos Nutricionais , França/epidemiologia , Humanos , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/prevenção & controle , Vitamina DRESUMO
BACKGROUND: Rheumatologists must contend with COVID-19 pandemic in the management of their patients and many questions have been raised on the use of both anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARD). The French Society of Rheumatology (SFR) selected the most critical ones to the daily practice of a rheumatologist and a group of 10 experts from SFR and Club Rheumatism and Inflammation (CRI) boards proposed responses based on the current knowledge of May 2020. METHODS: Following the availability of the first 18 questions and statements, 1400 individuals consulted the frequently asked questions between the March 31, 2020 and April 12, 2020. As a result, 16 additional questions were forwarded to the SFR, and answered by the board. An additional round of review by email and video conference was organized, which included updates of the previous statements. The scientific relevance of 5 of the questions led to their inclusion in this document. Each response received a final assessment on a scale of 0-10 with 0 meaning no agreement whatsoever and 10 being in complete agreement. The mean values of these votes for each question are presented as the levels of agreement (LoA) at the end of each response. This document was last updated on April 17, 2020. RESULTS: Based on current scientific literature already published, in most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. If signs suggestive of infection (coronavirus or other) occur, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms. Only, some signals suggest that people taking an immunosuppressive dose of corticosteroid therapy are at greater risk of developing severe COVID-19. Intra-articular injections of glucocorticoids are allowed when there is no reasonable therapeutic alternative, and providing that precautions to protect the patient and the practitioner from viral contamination are adopted, included appropriate information to the patient. CONCLUSIONS: Currently available data on managing patients with rheumatic diseases during the COVID-19 pandemic are reassuring and support continuing or initiating symptomatic as well as specific treatments of these diseases, the main target of their management remaining their appropriate control, even during this pandemic.
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Antirreumáticos/uso terapêutico , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Inquéritos e Questionários , COVID-19 , Infecções por Coronavirus/prevenção & controle , Técnica Delphi , Gerenciamento Clínico , Feminino , França/epidemiologia , Humanos , Controle de Infecções/métodos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Prognóstico , Estudos Retrospectivos , Doenças Reumáticas/diagnóstico , Reumatologia , Sociedades Médicas , Resultado do TratamentoRESUMO
The current health crisis caused by COVID-19 is a challenge for oncology treatment, especially when it comes to radiotherapy. Cancer patients are already known to be very fragile and COVID-19 brings about the risk of severe respiratory complications. In order to treat patients safely while protecting medical teams, the entire health care system must optimize the way it approaches prevention and treatment at a time when social distancing is key to stemming this pandemic. All indications and treatment modalities must be re-discussed. This is particularly the case for radiotherapy of bone metastases for which it is possible to reduce the number of sessions, the frequency of transport and the complexity of treatments. These changes will have to be discussed according to the organization of each radiotherapy department and the health situation, while medical teams must remain vigilant about the risks of complications of bone metastases, particularly spinal metastases. In this short piece, the members of the GEMO (the European Study Group of Bone Metastases) offer a number of recommendations to achieve the above objectives, both in general and in relation to five of the most common situations on radiation therapy for bone metastases.
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Standard adjuvant therapies for breast cancer such as chemotherapy or aromatase inhibitor and LH-RH agonist hormone therapy are associated with significant survival gains but also induce bone loss by aggravating the estrogen deprivation. The bone loss may be substantial, notably during early treatment, and occurs regardless of the baseline bone mineral density values. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on literature review, about osteoporosis prevention and treatment in these patients. The following scientific societies contributed to the work: Société Française de Rhumatologie (SFR), Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO), Groupe Européen d'Etudes des Métastases Osseuses (GEMO), Association Francophone pour les Soins Oncologiques de Support (AFSOS), Société Française de Sénologie et de Pathologie Mammaire (SFSPM), Société Française de Radiothérapie Oncologique (SFRO). Drug prescription and reimbursement modalities in France were taken into account. These recommendations apply to postmenopausal women taking systemic chemotherapy and/or aromatase inhibitor therapy, non-postmenopausal women taking LH-RH agonist therapy, and non-postmenopausal women with persistent amenorrhea 1 year after chemotherapy completion. All women in these three categories should undergo an evaluation of bone health and receive interventions to combat risk factors for bone loss. Patients with a history of severe osteoporotic fracture and/or a T-score value <-2.5 should receive osteoporosis drug therapy. The FRAX® score should be used to guide treatment decisions in patients whose T-score is between -1 and -2.5. General osteoporosis prevention measures should be applied in patients without criteria for osteoporosis drug therapy, who should undergo bone mineral density measurements 18-24 months later if the baseline T-score is<-1 and 3-5 years later if the baseline T-score is>-1. The anti-tumor effect of bisphosphonates and denosumab was not considered when establishing these recommendations.
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Adjuvantes Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Osteoporose/prevenção & controle , Guias de Prática Clínica como Assunto , Densidade Óssea , Quimioterapia Adjuvante/efeitos adversos , Feminino , França/epidemiologia , Humanos , Incidência , Osteoporose/induzido quimicamente , Osteoporose/epidemiologiaRESUMO
Androgen-deprivation therapy (ADT) in patients with prostate cancer can be achieved surgically or chemically, notably by prescribing LHRH analogs. Major bone loss occurs rapidly in both cases, due to the decrease in testosterone levels, and can increase the fracture risk. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on a literature review, about osteoporosis prevention and treatment in patients on ADT. The following scientific societies contributed to the work: Société française de rhumatologie (SFR), Groupe de recherche et d'information sur les ostéoporoses (GRIO), Groupe européen d'études des métastases osseuses (GEMO), Association francophone pour les soins de support (AFSOS), Association française d'urologie (AFU), Société française de radiothérapie oncologique (SFRO). Medication prescription and reimbursement modalities in France were taken into account. The recommendations state that a fracture-risk evaluation and interventions targeting risk factors for fractures should be provided to all patients on ADT. Those patients with a history of severe osteoporotic fracture and/or a T-score < -2.5 should receive osteoporosis therapy. Patients whose T-score is between -1.5 and -2.5 should be treated if they exhibit at least two other risk factors among the following: age ≥ 75 years, history of non-severe fracture after 50 years of age, body mass index < 19 kg/m2, at least three comorbidities (e.g., cardiovascular disease, depression, Parkinson's disease, and dementia), current glucocorticoid therapy, and repeated falls. When the decision is difficult, FRAX® score determination and an assessment by a bone disease specialist may be helpful. When osteoporosis therapy is not indicated, general measures should be applied, and bone mineral density measured again after 12-24 months. The anti-tumor effects of bisphosphonates and denosumab fall outside the scope of these recommendations.
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Antagonistas de Androgênios/efeitos adversos , Hormônio Liberador de Gonadotropina/uso terapêutico , Osteoporose/terapia , Fraturas por Osteoporose/terapia , Neoplasias da Próstata/terapia , Antagonistas de Androgênios/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/etiologia , Difosfonatos/uso terapêutico , França , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Masculino , Orquiectomia/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/etiologia , Osteoporose/prevenção & controle , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Medição de Risco , Fatores de RiscoRESUMO
A finding of high bone mineral density (BMD) from routine dual-energy X-ray absorptiometry (DXA) screening is not uncommon. No consensus exists about the definition of high BMD, and T-score and/or Z-score cutoffs of ≥+2.5 or ≥+4 have been suggested. The many disorders that can result in high BMD are usually classified based on whether the BMD changes are focal vs. generalized or acquired vs. constitutional. In over half the cases, careful interpretation of the DXA report and images identifies the cause as an artefact (e.g., degenerative spinal disease, vascular calcifications, or syndesmophytes) or focal lesion (e.g., sclerotic bone metastasis or Paget's disease). Generalized acquired high BMD may be secondary to a diverse range of disorders such as fluorosis, diffuse bone sclerosis related to renal osteodystrophy, hematological diseases, and hepatitis C. Identification of the cause may require additional investigations such as imaging studies, serum tryptase assay, or serological tests for the hepatitis C virus. Finally, high BMD is a feature of many genetic diseases, most notably osteopetrosis and the disorders caused by mutations in the sclerostin gene SOST (sclerosing bone dysplasia and van Buchem disease) or in the LRP5 gene encoding the low-density lipoprotein receptor-related protein 5 (which is the Wnt co-receptor).
Assuntos
Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Osteopetrose/diagnóstico , Absorciometria de Fóton , Adulto , Osso e Ossos/metabolismo , Saúde Global , Humanos , Incidência , Osteopetrose/epidemiologia , Osteopetrose/metabolismoRESUMO
OBJECTIVES: To update the 2012 recommendations on pharmacotherapy for postmenopausal osteoporosis, under the aegis of the Bone Task Force of the French Society for Rheumatology (SFR) and of the Osteoporosis Research and Information Group (GRIO), in collaboration with scientific societies (Collège national des généralistes enseignants, Collège national des gynécologues et obstétriciens français, Fédération nationale des collèges de gynécologie médicale, Groupe d'étude de la ménopause et du vieillissement hormonal, Société française de chirurgie orthopédique, Société française d'endocrinologie, and Société française de gériatrie et de gérontologie). METHODS: Updated recommendations were developed by a task force whose members represented the medical specialties involved in the management of postmenopausal osteoporosis. The update was based on a literature review and developed using the method advocated by the French National Authority for Health (HAS). DISCUSSION AND CONCLUSION: The updated recommendations place strong emphasis on the treatment of women with severe fractures, in whom the use of osteoporosis medications is recommended. All the available osteoporosis medications are suitable in patients with severe fractures; zoledronic acid deserves preference as the fist-line drug after a hip fracture. In patients with or without non-severe fractures, the decision to use osteoporosis medications is based on bone mineral density values and in challenging cases, on probabilities supplied by prediction tools such as FRAX®. All osteoporosis medications are suitable; raloxifene should be reserved for patients at low risk for peripheral fractures. The fracture risk should be reevaluated every 2 to 3 years to decide on the best follow-up treatment. These updated recommendations discuss the selection of first-line osteoporosis medications and treatment sequences.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Guias de Prática Clínica como Assunto , Absorciometria de Fóton/métodos , Idoso , Densidade Óssea , Gerenciamento Clínico , Feminino , Previsões , França , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/epidemiologia , Prognóstico , Medição de RiscoAssuntos
Oftalmopatia de Graves , Esclerite , Humanos , Esclerite/induzido quimicamente , Esclerite/diagnóstico , Esclerite/tratamento farmacológico , Ácido Zoledrônico/efeitos adversos , Oftalmopatia de Graves/induzido quimicamente , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/diagnóstico , ImunossupressoresRESUMO
OBJECTIVES: Long-term bisphosphonates exposure is a proven risk factor for atypical femoral fractures (AFF) but several cases occur in untreated patients. The identification of other risk factors for AFF is critical for the management of osteoporosis. We here assessed the genetic factors associated with AFF regardless of the treatment. METHODS: Cases were identified through ICD-10 codes in 3 academic centers. Medical records were analyzed by 2 investigators that adjudicated X-rays for typical or atypical fractures. Genetic screening for ALPL, SOX9, COL1A1 and COL1A2 variants was performed after patient's information and consent. RESULTS: A total of 389 cases were identified and 268 were ruled out according to the ASBMR Task Force recommendations. On the remaining 121, 14 (11.6%) were AFF. Anti-osteoporotic drugs were more frequent in the AFF group compared to the typical fracture group (35% vs 5%, P<0.001) but only 4 (28.6%) patients with AFF had been exposed to bisphosphonates. Genetic analysis performed in 5 patients found one with a heterozygous mutation in COL1A2 (rs72658163, NM_000089.3:c.2123G>A, p.Arg708Gln). This rare variant (Minor Allele Frequency=0.0008) causes a missense mutation that alters collagen fibrillogenesis. Eight heterozygous polymorphisms for ALPL were also found in 3 patients. CONCLUSION: Genetic screening for variants in only 4 genes and 5 patients with AFF resulted in the identification of genetic variants in 3 patients including a rare variant in COL1A2, suggesting a possible genetic susceptibility to AFF. This finding should encourage clinician to further genotype patients with AFF in a collaborative multicentric project.