RESUMO
OBJECTIVES: To compare the correlations of histological class inferences based on clinical manifestations and laboratory tests between rheumatologists and nephrologists, to determine the associations of clinical and laboratory data with histological classes and to develop an instrument that can assist histological class identification in lupus nephritis (LN). METHODS: Retrospective study based on medical records of 80 systemic lupus erythematosus patients (SLICC criteria classification, 2012) who underwent kidney biopsy between 2010 and 2017. Two rheumatologists and two nephrologists received clinical and laboratory data and answered questions regarding which histological class was expected on kidney biopsy. Kappa (K) coefficient was used to assess agreement between evaluators. A decision tree was constructed using the chi-square interaction detector and logistic regression was performed for the development of the proliferative histological class predictor instrument. RESULTS: The mean age and disease duration were 33 ± 10.3 years and 11.5 ± 6.7 years, respectively. The level of agreement between the evaluators and kidney biopsy was poor (global K 0.364 ± 0.029; p < .001). Analyzing clinical and laboratory variables as predictors of proliferative histological class, patients with abnormal urinary sediment and positive anti-dsDNA antibodies presented 13.96 and 4.96 times higher risks of presenting class III or IV, respectively (p < 0.001). Our instrument has a sensitivity of 87.8% and specificity of 80%, using abnormal urinary sediment, anti-dsDNA antibodies, and serum creatinine as variables. CONCLUSIONS: Rheumatologists and nephrologists with experience in treating LN generated evaluations that correlated weakly with kidney biopsy. When kidney biopsy is unavailable or is contraindicated for medical reasons, instruments based on clinical and laboratory predictors may be helpful.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Lúpus Eritematoso Sistêmico/patologia , Estudos Retrospectivos , Biópsia , Rim/patologiaRESUMO
OBJECTIVES: To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study-"The ReumaCoV Brazil"-designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post-COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04-5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12-96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10-16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97-15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12-0.88], p = 0.02). CONCLUSION: Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.
Assuntos
COVID-19 , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Estudos Transversais , Brasil/epidemiologia , Índice de Gravidade de Doença , SARS-CoV-2 , Ciclofosfamida/uso terapêuticoRESUMO
BACKGROUND: Myostatin is a protein in the TGF-ß family that negatively regulates muscle mass, and follistatin is a myostatin antagonist. OBJECTIVE: The aim of this study was to measure serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients and correlate these levels with muscle strength, fatigue, functional capacity, damage, and serum levels of muscle enzymes. METHODS: This was a multicenter cross-sectional study including 50 patients (34 dermatomyositis and 16 polymyositis [PM]) and 52 healthy individuals (control group [CG]). The disease status was evaluated according to the International Myositis Assessment & Clinical Studies. Fatigue was rated according to the Fatigue Severity Scale, and body composition was measured using dual-energy x-ray emission densitometry. Myostatin and follistatin were measured using enzyme-linked immunosorbent assays. RESULTS: Mean age was 50.9 ± 14.0 years, and mean disease duration was 89.2 ± 80.9 months. There were no differences in levels of myostatin (14.15 ± 9.65 vs. 10.97 ± 6.77 ng/mL; p = 0.131) or follistatin (0.53 ± 0.71 vs. 0.49 ± 0.60 ng/mL; p = 0.968) between patients and the CG. However, myostatin levels were higher in PM than CG (16.9 ± 12.1 vs. 11.0 ± 6.8 ng/mL; p = 0.036). There was no difference in serum myostatin among patients with and without low lean mass. Patients not treated with corticosteroids had higher serum levels of myostatin than the CG. There was a weak negative correlation between follistatin and Manual Muscle Testing and a Subset of Eight Muscles and a weak positive correlation between follistatin and Healthy Assessment Questionnaire. CONCLUSIONS: Serum levels of myostatin and follistatin did not differ between dermatomyositis and PM patients and control subjects. The assessment of serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients seems not to be helpful in clinical practice.
Assuntos
Dermatomiosite , Folistatina/sangue , Miostatina/sangue , Polimiosite , Adulto , Estudos Transversais , Dermatomiosite/diagnóstico , Humanos , Pessoa de Meia-Idade , Polimiosite/diagnósticoRESUMO
BACKGROUND: Vessel wall inflammation, atherosclerosis and hypercoagulability may be responsible for ischemic events in Takayasu arteritis (TA). No study has evaluated the effect of antiplatelet therapy for the prevention of ischemic events in TA. METHODS AND RESULTS: Forty-eight patients who met the ACR Classification Criteria for TA under follow-up at the Vasculitis Unit of Universidade Federal de São Paulo were evaluated retrospectively for clinical manifestations, therapy and arterial ischemic events. The mean age at study was 38.0 years and the mean age at TA diagnosis was 29.1 years. Women comprised for 89.6% of patients and 60.4% were Caucasian. Risk factors for cardiovascular disease were found in 44 patients (91.7%) The most common comorbidities for TA patients were hypertension (77.1%), high low-density lipoprotein (45.8%) and obesity (16.7%). Antiplatelet therapy was used by 62.5% of patients whereas anticoagulants were used by 12.5%. Acute ischemic events occurred in 29.2% of patients. TA patients with ischemic events used significantly less antiplatelet agents (14.3%) than those without ischemic events (82.4%), P<0.0001. No difference concerning ischemic events was observed in patients on anticoagulant therapy (P=0.339). The 3 deaths of TA patients were observed only in those who had presented ischemic events (P=0.021). Antiplatelet agents had a protective effect against ischemic events (hazard ratio =0.055, 95% confidence interval: 0.06-0.514; P=0.011). CONCLUSIONS: Antiplatelet therapy is associated with a lower frequency of ischemic events in patients with TA.
Assuntos
Artérias/patologia , Isquemia/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Adolescente , Adulto , Anticoagulantes/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Comorbidade , Feminino , Humanos , Isquemia/tratamento farmacológico , Masculino , Estudos Retrospectivos , Fatores de Risco , Arterite de Takayasu/patologia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This study included 99 patients diagnosed with RA American College of Rheumatology, 1987), on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T) or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28) occurred (inadequate response: IR). In case of IR, the patient was considered as primary failure (PF). Secondary failure (SF) was defined as loss of response after initial improvement. Remission (DAS28 < 2.6), low disease activity (between 2.61 and 3.2), and functional improvement [increase in the initial Health Assessment Questionnaire (HAQ) > 0.2] were assessed by use of linear regression analysis. The significance level adopted was P < 0.05. RESULTS: Switching was performed in 39 (39.4%) patients, especially due to PF (24.3%), SF (35.1%) and T (40.5%). The retention rate of the first agent was 60.1%, and the mean time for switching was 14.2 ± 10.9 months. After switching, a tendency towards a decrease in DAS28 was observed (4.7 ± 1.4; P = 0.08), but not in the HAQ (1.2 ± 0.77; P = 0.11). Around 43% of the patients achieved good/moderate EULAR response. The major determinant of switching was a higher initial DAS28, independent of age, duration of disease, and functional capacity. CONCLUSION: Switching between anti-TNF-alpha agents is a valid strategy to control disease activity, despite the low likelihood of remission and no significant improvement in functional capacity.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Substituição de Medicamentos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
TNF blockers have been used in the treatment of several types of chronic inflammatory arthritis, especially rheumatoid arthritis. However, many doubts regarding the safety and high risk of infectious diseases in these patients remain. The main objective of this report was to present a case of lepromatous leprosy in a rheumatoid arthritis patient using TNF blockers. The development of adverse events should be rigorously observed, especially those related to infectious agents. Thus, appropriate investigation of skin lesions in patients receiving anti-TNFα therapy is recommended, as the initial clinical manifestation may be unusual, particularly in endemic regions in Brazil.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Hanseníase Virchowiana/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Anticorpos Monoclonais Humanizados , Humanos , MasculinoRESUMO
OBJECTIVE: To estimate the prevalence and analyze risk factors associated to osteoporosis and low-trauma fracture in women. METHODS: Cross-sectional study including a total of 4,332 women older than 40 attending primary care services in the Greater São Paulo, Southeastern Brazil, between 2004 and 2007. Anthropometrical and gynecological data and information about lifestyle habits, previous fracture, medical history, food intake and physical activity were obtained through individual quantitative interviews. Low-trauma fracture was defined as that resulting from a fall from standing height or less in individuals 50 years or older. Multiple logistic regression models were designed having osteoporotic fracture and bone mineral density (BMD) as the dependent variables and all other parameters as the independent ones. The significance level was set at p<0.05. RESULTS: The prevalence of osteoporosis and osteoporotic fractures was 33% and 11.5%, respectively. The main risk factors associated with low bone mass were age (OR=1.07; 95% CI: 1.06;1.08), time since menopause (OR=2.16; 95% CI: 1.49;3.14), previous fracture (OR=2.62; 95% CI: 2.08;3.29) and current smoking (OR=1.45; 95% CI: 1.13;1.85). BMI (OR=0.88; 95% CI: 0.86;0.89), regular physical activity (OR=0.78; 95% CI: 0.65;0.94) and hormone replacement therapy (OR=0.43; 95% CI: 0.33;0.56) had a protective effect on bone mass. Risk factors significantly associated with osteoporotic fractures were age (OR=1.05; 95% CI: 1.04;1.06), time since menopause (OR=4.12; 95% CI: 1.79;9.48), familial history of hip fracture (OR=3.59; 95% CI: 2.88;4.47) and low BMD (OR=2.28; 95% CI: 1.85;2.82). CONCLUSIONS: Advanced age, menopause, low-trauma fracture and current smoking are major risk factors associated with low BMD and osteoporotic fracture. The clinical use of these parameters to identify women at higher risk for fractures might be a reasonable strategy to improve the management of osteoporosis.
Assuntos
Densidade Óssea , Fraturas Ósseas/etiologia , Osteoporose/complicações , Brasil/epidemiologia , Estudos Transversais , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Prevalência , Fatores de Risco , População UrbanaRESUMO
OBJETIVOS: Avaliar a resposta clínica após a estratégia de troca entre agentes antifator de necrose tumoral alfa (anti-TNF-alfa) em pacientes com artrite reumatoide (AR). PACIENTES E MÉTODOS: Foram incluídos 99 pacientes com diagnóstico de AR (American College of Rheumatology, 1987), em uso de terapia anti-TNF-alfa, para avaliação da resposta terapêutica após 24 semanas. A estratégia de troca foi feita se, após 12 a 24 semanas, houvesse relato de evento adverso sério (T: toxicidade) ou se não ocorresse redução maior que 0,6 do índice de atividade da doença (DAS28) inicial (RI: resposta inadequada). Nesse último caso, o paciente foi considerado como falência primária (FP). Falência secundária (FS) foi definida se houvesse perda de resposta após melhora inicial. Remissão (DAS28 < 2,6), baixa atividade de doença (2,61 < 3,2) e melhora funcional [aumento > 0,2 do questionário de avaliação da saúde (HAQ) inicial] foram avaliadas por análise de regressão linear. P < 0,05 foi considerado significante. RESULTADOS: A estratégia de troca foi realizada em 39 (39,4 por cento) pacientes, especialmente por FP (24,3 por cento), FS (35,1 por cento) e T (40,5 por cento). A taxa de retenção ao primeiro agente foi de 60,1 por cento, e o tempo médio para a troca foi de 14,2 ± 10,9 meses. Após a troca, houve tendência à queda do DAS28 (4,7 ± 1,4; P = 0,08), mas não do HAQ (1,2 ± 0,77; P = 0,11). Cerca de 43 por cento deles alcançaram boa/moderada resposta EULAR. O principal determinante da troca foi o DAS28 inicial mais elevado, independente de idade, tempo de doença e capacidade funcional. CONCLUSÃO: A estratégia de troca entre agentes anti-TNF-alfa é válida para o controle da atividade de doença, embora com baixa probabilidade de remissão e sem melhora significativa da capacidade funcional.
OBJECTIVES: To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This study included 99 patients diagnosed with RA American College of Rheumatology, 1987), on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T) or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28) occurred (inadequate response: IR). In case of IR, the patient was considered as primary failure (PF). Secondary failure (SF) was defined as loss of response after initial improvement. Remission (DAS28 < 2.6), low disease activity (between 2.61 and 3.2), and functional improvement [increase in the initial Health Assessment Questionnaire (HAQ) > 0.2] were assessed by use of linear regression analysis. The significance level adopted was P < 0.05. RESULTS: Switching was performed in 39 (39.4 percent) patients, especially due to PF (24.3 percent), SF (35.1 percent) and T (40.5 percent). The retention rate of the first agent was 60.1 percent, and the mean time for switching was 14.2 ± 10.9 months. After switching, a tendency towards a decrease in DAS28 was observed (4.7 ± 1.4; P = 0.08), but not in the HAQ (1.2 ± 0.77; P = 0.11). Around 43 percent of the patients achieved good/moderate EULAR response. The major determinant of switching was a higher initial DAS28, independent of age, duration of disease, and functional capacity. CONCLUSION: Switching between anti-TNF-alpha agents is a valid strategy to control disease activity, despite the low likelihood of remission and no significant improvement in functional capacity.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Substituição de Medicamentos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A terapia anti-TNFα tem sido amplamente utilizada em diversas artropatias inflamatórias crônicas, em especial artrite reumatoide (AR). No entanto, há preocupações quanto à segurança e ao risco de doenças infecciosas nos pacientes. O objetivo deste artigo é descrever um caso de hanseníase, forma virchowiana, em paciente com AR em uso de terapia anti-TNFα. Dessa forma, a vigilância dos eventos adversos deve ser rigorosa, especialmente no que diz respeito às doenças infecciosas. É recomendada investigação apropriada de lesões cutâneas em paciente recebendo terapia anti-TNFα, visto que o quadro clínico inicial pode ser inespecífico, especialmente em regiões endêmicas como o Brasil.
TNF blockers have been used in the treatment of several types of chronic inflammatory arthritis, especially rheumatoid arthritis. However, many doubts regarding the safety and high risk of infectious diseases in these patients remain. The main objective of this report was to present a case of lepromatous leprosy in a rheumatoid arthritis patient using TNF blockers. The development of adverse events should be rigorously observed, especially those related to infectious agents. Thus, appropriate investigation of skin lesions in patients receiving anti-TNFa therapy is recommended, as the initial clinical manifestation may be unusual, particularly in endemic regions in Brazil.
Assuntos
Adulto , Humanos , Masculino , Anticorpos Monoclonais/efeitos adversos , Hanseníase Virchowiana/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVE: To estimate the prevalence and analyze risk factors associated to osteoporosis and low-trauma fracture in women. METHODS: Cross-sectional study including a total of 4,332 women older than 40 attending primary care services in the Greater São Paulo, Southeastern Brazil, between 2004 and 2007. Anthropometrical and gynecological data and information about lifestyle habits, previous fracture, medical history, food intake and physical activity were obtained through individual quantitative interviews. Low-trauma fracture was defined as that resulting from a fall from standing height or less in individuals 50 years or older. Multiple logistic regression models were designed having osteoporotic fracture and bone mineral density (BMD) as the dependent variables and all other parameters as the independent ones. The significance level was set at p<0.05. RESULTS: The prevalence of osteoporosis and osteoporotic fractures was 33 percent and 11.5 percent, respectively. The main risk factors associated with low bone mass were age (OR=1.07; 95 percent CI: 1.06;1.08), time since menopause (OR=2.16; 95 percent CI: 1.49;3.14), previous fracture (OR=2.62; 95 percent CI: 2.08;3.29) and current smoking (OR=1.45; 95 percent CI: 1.13;1.85). BMI (OR=0.88; 95 percent CI: 0.86;0.89), regular physical activity (OR=0.78; 95 percent CI: 0.65;0.94) and hormone replacement therapy (OR=0.43; 95 percent CI: 0.33;0.56) had a protective effect on bone mass. Risk factors significantly associated with osteoporotic fractures were age (OR=1.05; 95 percent CI: 1.04;1.06), time since menopause (OR=4.12; 95 percent CI: 1.79;9.48), familial history of hip fracture (OR=3.59; 95 percent CI: 2.88;4.47) and low BMD (OR=2.28; 95 percent CI: 1.85;2.82). CONCLUSIONS: Advanced age, menopause, low-trauma fracture and current smoking are major risk factors associated with low BMD and osteoporotic fracture. The clinical use of these parameters to identify women at higher risk for...
OBJETIVO: Estimar a prevalência e analisar os fatores de risco associados com osteoporose e fratura por baixo impacto entre mulheres. MÉTODOS: Estudo transversal realizado com 4.332 mulheres acima de 40 anos de idade provenientes de atendimento primário de saúde na área metropolitana da Grande São Paulo, SP, entre 2004 e 2007. Dados antropométricos e ginecológicos e relativos a hábitos de vida, fratura prévia, antecedentes pessoais, ingestão alimentar e atividade física foram avaliados por meio de entrevista individual e quantitativa. Fratura por baixo impacto foi definida como decorrente de queda da própria altura ou menos em indivíduos com mais de 50 anos de idade. Modelos de regressão multivariada e logística analisaram, respectivamente, a densidade óssea e a fratura por osteoporose como variáveis dependentes e todas as outras como independentes. O nível de significância estatística estabelecido foi p < 0,05. RESULTADOS: A prevalência de osteoporose e de fraturas por fragilidade óssea foi de 33 por cento e 11,5 por cento, respectivamente. Os principais fatores de risco associados com baixa densidade óssea foram idade (OR = 1,07; IC 95 por cento: 1,06;1,08), menopausa (OR = 2,16; IC 95 por cento: 1,49;3,14), fratura prévia (OR = 2,62; IC 95 por cento: 2,08;3,29) e tabagismo atual (OR = 1,45; IC 95 por cento: 1,13;1,85). Por outro lado, elevado IMC (OR = 0,88; IC 95 por cento: 0,86;0,89), atividade física regular (OR = 0,78; IC 95 por cento: 0,65;0,94) e terapia hormonal atual (OR = 0,43; IC 95 por cento: 0,33;0,56) desempenharam papel protetor. Os fatores de risco significativamente relacionados com fratura por osteoporose foram idade (OR = 1,05; IC 95 por cento: 1,04;1,06), menopausa (OR = 4,12; IC 95 por cento: 1,79;9,48), história familiar de fratura de quadril (OR = 3,59; IC 95 por cento: 2,88;4,47) e baixa densidade óssea (OR = 2,28; IC 95 por cento: 1,85;2,82). CONCLUSÕES: Idade avançada, menopausa, fratura prévia por baixo impacto...
OBJETIVO: Estimar la prevalencia y analizar los factores de riesgo asociados con osteoporosis y fractura por bajo impacto entre mujeres. MÉTODOS: Estudio transversal realizado con 4.332 mujeres encima de 40 años de edad provenientes de atención primaria de salud en el área metropolitana de la gran Sao Paulo, SP, entre 2004 2007. Datos antropométricos y ginecológico y relativos a hábitos de vida, fractura previa, antecedentes personales, ingestión alimentaria y actividad física fueron evaluados por medio de entrevista individual y cuantitativa. Fractura por bajo impacto fue definida como decurrente de caída de la propia altura o menos en individuos con más de 50 años de edad. Modelos de regresión multivariada y logística analizaron, respectivamente, la densidad ósea y la fractura por osteoporosis, como variables dependientes y todas las otras como independientes. El nivel de significancia estadística establecido fue p<0,05. RESULTADOS: La prevalencia de osteoporosis y de fracturas por fragilidad ósea fue de 33 por ciento y 11,5 por ciento, respectivamente. Los principales factores de riesgo asociados con baja densidad ósea fueron edad (OR=1,07; IC 95 por ciento: 1,06;1,08), menopausia (OR=2,16; IC 95 por ciento: 1,49;3,14), fractura previa (OR=2,62; IC 95 por ciento: 2,08;3,29) y tabaquismo actual (OR=1,45; IC 95 por ciento: 1,13;1,85). Por otro lado, elevado IMC (OR=0,88; IC 95 por ciento: 0,86;0,89), actividad física regular (OR=0,78; IC 95 por ciento: 0,65;0,94) y terapia hormonal actual (OR=0,43; IC 95 por ciento: 0,33;0,56) desempeñaron papel protector. Los factores de riesgo significantemente relacionados con fractura por osteoporosis fueron edad (OR=1,05; IC 95 por ciento: 1,04;1,06), menopausia (OR=4,12; IC 95 por ciento: 1,79;9,48), historia familiar de fractura de cuadril (OR=3,59; IC 95 por ciento: 2,88;4,47) y baja densidad ósea (OR=2,28; IC 95 por ciento: 1,85;2,82). CONCLUSIONES: Edad avanzada, menopausia, fractura previa...