Lineamientos para la prevención y el tratamiento de la osteoporosis inducida por glucocorticoides en pediatría / Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis in pediatrics

Objetivo. Proporcionar un marco para profesionales de la salud que tratan a pacientes pediátricos bajo terapia con glucocorticoides (GC) y desarrollar recomendaciones para la prevención y el tratamiento de la osteoporosis inducida por GC en la población pediátrica. Métodos. Un panel de expertos en enfermedades óseas y pediátricas generó una serie de preguntas PICO que abordan aspectos relacionados con la prevención y el tratamiento de osteoporosis en pacientes bajo tratamiento con GC. Siguiendo la metodología GRADE, se realizó una revisión sistemática de la literatura, se resumieron las estimaciones del efecto y se calificó la calidad de la evidencia. Luego se procedió a la votación y a la formulación de las recomendaciones. Resultados. Se desarrollaron 7 recomendaciones y 6 principios generales para osteoporosis inducida por GC en población pediátrica. Conclusión. Estas recomendaciones proporcionan orientación para los médicos que deben tomar decisiones en pacientes pediátricos bajo tratamiento con GC.

Objective. To provide a framework for healthcare professionals managing pediatric patients who are on active glucocorticoid (GC) therapy and to develop recommendations for the prevention and treatment of GC-induced osteoporosis in the pediatric population. Methods. A panel of experts on bone and pediatric diseases developed a series of PICO questions that address issues related to the prevention and treatment of osteoporosis in patients on GC therapy. In accordance with the GRADE approach, we conducted a systematic review of the literature, summarized effect estimations, and classified the quality of the evidence. Then, voting and the formulation of recommendations followed. Results. Seven recommendations and six general principles were developed for GC-induced osteoporosis in the pediatric population. Conclusion. These recommendations provide guidance for clinicians who must make decisions concerning pediatric patients undergoing treatment with GC.

Resveratrol Alleviates Osteoporosis by Promoting Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells via SITR1/PI3K/AKT Pathway / El Resveratrol Alivia la Osteoporosis al Promover la Diferenciación Osteogénica de las Células Madre Mesenquimales de la Médula Ósea a Través de la Vía SITR1/PI3K/AKT

SUMMARY: Senile osteoporosis is mainly caused by reduced osteoblast differentiation and has become the leading cause of fractures in the elderly worldwide. Natural organics are emerging as a potential option for the prevention and treatment of osteoporosis. This study was designed to study the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis mice. A mouse model of osteoporosis was established by subcutaneous injection of dexamethasone and treated with resveratrol administered by gavage. In vivo and in vitro, we used western blot to detect protein expression, and evaluated osteogenic differentiation of BMSCs by detecting the expression of osteogenic differentiation related proteins, calcium deposition, ALP activity and osteocalcin content. Resveratrol treatment significantly increased the body weight of mice, the level of serum Ca2+, 25(OH)D and osteocalcin, ration of bone weight, bone volume/total volume, trabecular thickness, trabecular number, trabecular spacing and cortical thickness in osteoporosis mice. In BMSCs of osteoporosis mice, resveratrol treatment significantly increased the expression of Runx2, osterix (OSX) and osteocalcin (OCN) protein, the level of calcium deposition, ALP activity and osteocalcin content. In addition, resveratrol treatment also significantly increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT in BMSCs of osteoporosis mice. In vitro, resveratrol increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT, Runx2, OSX and OCN protein, the level of calcium deposition, ALP activity and osteocalcin content in BMSCs in a concentration-dependent manner, while SIRT1 knockdown significantly reversed the effect of resveratrol. Resveratrol can attenuate osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells, and the mechanism may be related to the regulation of SIRT1/PI3K/AKT pathway.

La osteoporosis senil es causada principalmente por una diferenciación reducida de osteoblastos y se ha convertido en la principal causa de fracturas en las personas mayores en todo el mundo. Los productos orgánicos naturales están surgiendo como una opción potencial para la prevención y el tratamiento de la osteoporosis. Este estudio fue diseñado para estudiar el efecto del resveratrol en la diferenciación osteogénica de las células madre mesenquimales de la médula ósea (BMSC) en ratones con osteoporosis. Se estableció un modelo de osteoporosis en ratones mediante inyección subcutánea de dexametasona y se trató con resveratrol administrado por sonda. In vivo e in vitro, utilizamos Western blot para detectar la expresión de proteínas y evaluamos la diferenciación osteogénica de BMSC detectando la expresión de proteínas relacionadas con la diferenciación osteogénica, la deposición de calcio, la actividad de ALP y el contenido de osteocalcina. El tratamiento con resveratrol aumentó significativamente el peso corporal de los ratones, el nivel sérico de Ca2+, 25(OH)D y osteocalcina, la proporción de peso óseo, el volumen óseo/ volumen total, el espesor trabecular, el número trabecular, el espaciado trabecular y el espesor cortical en ratones con osteoporosis. En BMSC de ratones con osteoporosis, el tratamiento con resveratrol aumentó significativamente la expresión de las proteínas Runx2, osterix (OSX) y osteocalcina (OCN), el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina. Además, el tratamiento con resveratrol también aumentó significativamente la expresión de SIRT1, p-PI3K/PI3K y p-AKT/AKT en BMSC de ratones con osteoporosis. In vitro, el resveratrol aumentó la expresión de las proteínas SIRT1, p-PI3K/PI3K y p- AKT/AKT, Runx2, OSX y OCN, el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina en BMSC de manera dependiente de la concentración, mientras que La caída de SIRT1 revirtió significativamente el efecto del resveratrol. El resveratrol puede atenuar la osteoporosis al promover la diferenciación osteogénica de las células madre mesenquimales de la médula ósea, y el mecanismo puede estar relacionado con la regulación de la vía SIRT1/PI3K/AKT.

Estudo retrospectivo de estimativa de idade óssea através da maturação cervical por meio de tomografia computadorizada de feixe cônico (TCFC) / Retrospective study of bone age estimation through cervical maturation using cone-beam computed tomography (CBCT)

Estimar idade óssea em pacientes é de suma importância para estabelecer um protocolo de tratamento adequado e ainda subsidiar outras análises e mesmo decisões de natureza administrativa, policial ou forense. A tomografia computadorizada por feixe cônico TCFC, dentre várias aplicações, pode ser um meio de obtenção de dados para estimativa de idade óssea em pacientes jovens. O objetivo do estudo foi, além de avaliar a acurácia do método de Baccetti et al. (2005) para obtenção do índice de maturação cervical (IMC) das vértebras cervicais C2, C3 e C4, obter por meio de medidas de área vertebral e intervertebral C2-C4 em plano sagital de tomografia computadorizada por feixe cônico (TCFC), uma fórmula de regressão que possa ser utilizada amplamente para a estimativa da idade entre 10 e 18 anos completos. Foram analisadas tomografias de 73 pacientes no intervalo etário de interesse, obtidas medidas de área em corpo de vértebra e espaços intervertebrais e estabelecidos índices IMC para cada um. Regressão linear simples foi realizada e duas fórmulas foram obtidas com poder explicativo de 59% da distribuição (R2) considerado o erro padrão de 1,3 anos (NC 95%). Em pós-teste considerada a margem de erro de 1,5 anos verificou-se um índice de acerto de 74% na predição da idade cronológica. Os dados de IMC obtidos neste estudo não foram satisfatórios e não demonstraram boa correlação com a progressão etária entre 10 e 18 anos de idade. Observados os propósitos e os limites deste trabalho, concluímos que a TCFC pode e deve ser utilizada para estimativa de idade óssea em indivíduos em crescimento.

Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

Climatério e lúpus eritematoso sistêmico / Climacteric and systemic lupus erythematosus

O lúpus eritematoso sistêmico é uma doença crônica, complexa e multifatorial que apresenta manifestações em vários órgãos. O seu acometimento ocorre 10 vezes mais no sexo feminino do que no masculino. É uma doença com uma clínica variada e com graus variados de gravidade, causando fadiga, manifestações cutâneas, como rash malar, fotossensibilidade, queda de cabelo e manifestações musculoesqueléticas, como artralgia, mialgia e atrite. Podem ocorrer flares (crises), que se caracterizam por aumento mensurável na atividade da doença. No climatério, no período da pré-menopausa, o lúpus eritematoso sistêmico ocorre com mais frequência, podendo ocorrer também na pós-menopausa. Algumas doenças são mais frequentes na fase do climatério, e a presença do lúpus pode influenciar na sua evolução, como a doença cardiovascular, osteoporose e tromboembolismo venoso. A terapia hormonal oral determina aumento do risco de tromboembolismo venoso no climatério, e na paciente com lúpus eritematoso sistêmico há aumento dos riscos de flares e de trombose. Em vista disso, a terapia hormonal é recomendada apenas para pacientes com lúpus eritematoso sistêmico estável ou inativo, sem história de síndrome antifosfolípides e com anticorpos antifosfolípides negativa, devendo-se dar preferência para a terapia estrogênica transdérmica, em menor dose e de uso contínuo. Na paciente com lúpus eritematoso sistêmico ativo ou com história de síndrome antifosfolípides ou com anticorpos antifosfolípides positiva, recomenda-se a terapia não hormonal, como os antidepressivos. (AU)

Systemic lupus erythematosus is a chronic, complex, multifactorial disease that manifests in several organs. Its involvement occurs 10 times more in females than in males. It is a disease with a varied clinic and varying degrees of severity, causing fatigue, skin manifestations such as malar rash, photosensitivity, hair loss and musculoskeletal manifestations such as arthralgia, myalgia and arthritis. Flare may occur, which are characterized by measurable increase in disease activity. In the climacteric, in the premenopausal period, systemic lupus erythematosus occurs more frequently, and may also occur in the postmenopausal period. Some diseases are more frequent in the Climacteric phase and the presence of lupus can influence its evolution, such as cardiovascular disease, osteoporosis and venous thromboembolism. Oral hormone therapy determines an increased risk of venous thromboembolism in the climacteric and in patients with systemic lupus erythematosus there is an increased risk of flares and thrombosis. In view of this, hormone therapy is only recommended for patients with stable or inactive systemic lupus erythematosus, without a history of antiphospholipid syndrome and with antiphospholipid antibodies, giving preference to transdermal estrogen therapy, at a lower dose and for continuous use. In patients with active systemic lupus erythematosus or with a history of antiphospholipid syndrome or positive antiphospholipid antibodies, non-hormonal therapy, such as antidepressants, is recommended. (AU)

Comparative Analysis of TNF-alpha, TNF-R1, and TNF-R2 in Patients with Low-impact Fractures Due to Osteoporosis / Análise comparativa de TNF-alfa, TNF-R1 e TNF-R2 em pacientes com fraturas de baixo impacto decorrentes de osteoporose

Abstract Objective To analyze the serum levels of TNF-alpha and its TNF-R1 and TNF-R2 receptors in the blood of patients with low-impact fractures due to osteoporosis, comparing between genders and with healthy patients. Methods The present study was conducted with a blood sample of 62 patients, divided into patients with osteoporosis and healthy patients. The results were obtained using the ELISA method. Cytokine concentrations were determined based on the absorbance values obtained. Results Serum TNF-alpha levels were undetectable in female patients, while in males they were found only in one patient, with no significant difference. Similar results were found in the analyses of TNF-R1 and TNF-R2 levels, a significant increase in levels of TNF-alpha receptors in the groups of patients with osteoporosis compared with the control groupinbothsexes.There wasnosignificant difference between the sexes in the dosage of both receptors within the group with osteoporosis. There was also a positive and significant correlation in the levels of TNF-R1 and TNF-R2 only in women. Conclusion The significant increase in TNF-R1 and TNF-R2 levels in women with osteoporosis suggest that the release and expression of these receptors may be contributing differently to the development of osteoporosis in men and women.

Resumo Objetivo Analisar os níveis séricos de TNF-alfa e de seus receptores TNF-R1 e TNF-R2 no sangue de pacientes com fraturas de baixo impacto, decorrentes de osteoporose, comparando entre os sexos e com pacientes saudáveis. Métodos Oestudofoi realizadocom amostradesanguede 62 pacientes,divididos em pacientes com osteoporose e pacientes saudáveis. Os resultados foram obtidos através do método de ELISA. As concentrações de citocinas foram determinadas com base nos valores de absorbância obtidos. Resultados Os níveis séricos de TNF-alfa foram indetectáveis nos pacientes do sexo feminino, enquanto no masculino encontrou-se somente em um paciente, não havendo diferença significativa. Encontrou-se resultados semelhantes nas análises dos níveis de TNF-R1 e TNF-R2, aumento significativo nos níveis dos receptores de TNF-alfa nos grupos de pacientes com osteoporose em comparação com o grupo controle, em ambos os sexos. Não houve diferença significativa entre os sexos na dosagem de ambos os receptores dentro do grupo com osteoporose. Houve ainda correlação positiva e significativa nos níveis de TNF-R1 e TNF-R2 apenas nas mulheres. Conclusão O aumento significativo nos níveis de TNF-R1 e TNF-R2 em mulheres com osteoporose sugerem que a liberação e expressão destes receptores pode estar contribuindo de maneira distinta no desenvolvimento da osteoporose em homens e mulheres.

Participação plurissocial para aumentar a inclusão e a assertividade nas tomadas de decisão em saúde relacionadas a tratamentos da osteoporose / Pluri-social participation to increase inclusion and assertiveness in health decision-making related to osteoporosis treatments

Embora as fraturas por fragilidade sejam importantes detratoras de qualidade de vida relacionada à saúde, aumentando a morbimortalidade e acarretando alto impacto clínico, psicossocial e econômico, elas são pouco valorizadas e negligenciadas por médicos e até mesmo por pacientes. Além disso, os critérios de priorização para avaliação de novas tecnologias, em geral, não consideram critérios além dos financeiros para uma tomada de decisão mais inclusiva e assertiva para o tratamento da população de mais alto risco de fratura. Assim, este artigo visa revisitar alguns diferentes pontos de vista e trazer uma reflexão sobre critérios e prioridades na osteoporose. Para isso, foi considerada a perspectiva de múltiplos atores no processo de tomada de decisão em saúde, bem como analisadas as falhas na atenção a uma doença de alta prevalência e que, além do grande impacto econômico gerado para a sociedade, causa repercussões emocionais, incapacidade gerada por fraturas e medo de novas quedas ou pequenos traumas.

Although fragility fractures are important detractors of health-related quality of life, increasing morbidity and mortality and causing a high clinical, psychosocial, and economic impact, they are undervalued and neglected by physicians and even patients. In addition, prioritization criteria for evaluating new technologies, in general, do not consider criteria other than financial ones for a more inclusive and assertive decision-making for the treatment of the population at higher risk of fracture. Thus, this article aims to revisit some different points of view and bring a reflection on criteria and priorities in osteoporosis. For this, the perspective of multiple stakeholders in the health decision-making process was considered, as well as the failures in the care of this highly prevalent disease that, in addition to the great economic impact generated for society, causes emotional repercussions, disability generated by fractures and fear of further falls or minor trauma.

The Relationship between Bone Mineral Densitometry and Visceral Adiposity Index in Postmenopausal Women / A relação entre a densitometria mineral óssea e o índice de adiposidade visceral em mulheres na pós-menopausa

Abstract Objective It was aimed to compare visceral adiposity index (VAI) levels in patients with normal bone mineral density (BMD), osteopenia, and osteoporosis. Methods One hundred twenty postmenopausal women (40 with normal BMD, 40 with osteopenia, and 40 with osteoporosis) between the ages of 50 to 70 years were included in the study. For females, the VAI was calculated using the formula (waist circumference [WC]/[36.58 + (1.89 x body mass index (BMI))]) x (1.52/High-density lipoprotein [HDL]-cholesterol [mmol/L]) x (triglyceride [TG]/0.81 [mmol/L]). Results The time of menopause from the beginning was similar in all groups. Waist circumference was found to be higher in those with normal BMD than in the osteopenic and osteoporotic groups (p = 0.018 and p < 0.001, respectively), and it was also higher in the osteopenic group than in the osteoporotic group (p = 0.003). Height and body weight, BMI, blood pressure, insulin, glucose, HDL-cholesterol, and homeostasis model assessment-insulin resistance (HOMA-IR) levels were similar in all groups. Triglyceride levels were found to be higher in the normal BMD group, compared with the osteoporotic group (p = 0.005). The level of VAI was detected as higher in those with normal BMD, compared with the women with osteoporosis (p = 0.002). Additionally, the correlation analysis showed a positive correlation between dual-energy X-ray absorptiometry (DXA) spine T-scores, WC, VAI, and a negative correlation between DXA spine T-scores and age. Conclusion In our study, we found higher VAI levels in those with normal BMD, compared with women with osteoporosis. We consider that further studies with a larger sample size will be beneficial in elucidating the entity.

Resumo Objetivo O objetivo foi comparar os níveis de índice de adiposidade visceral (IVA) em pacientes com densidade mineral óssea (DMO) normal osteopenia e osteoporose. Métodos Cento e vinte mulheres na pós-menopausa (40 com DMO normal 40 com osteopenia e 40 com osteoporose) com idades entre 50 e 70 anos foram incluídas no estudo. Para o sexo feminino o VAI foi calculado pela fórmula (circunferência da cintura [CC]/[36 58 + (1 89 x índice de massa corporal (IMC))]) x (1 52/lipoproteína de alta densidade [HDL]-colesterol [mmol/L]) x (triglicerídeo [TG]/0 81 [mmol/L]). Resultados O tempo de menopausa desde o início foi semelhante em todos os grupos. A circunferência da cintura foi maior naqueles com DMO normal do que nos grupos osteopênicos e osteoporóticos (p = 0 018 e p < 0 001 respectivamente) e também foi maior no grupo osteopênico do que no grupo osteoporótico (p = 0 003) . Altura e peso corporal IMC pressão arterial insulina glicose HDL-colesterol e os níveis de avaliação do modelo de homeostase-resistência à insulina (HOMA-IR) foram semelhantes em todos os grupos. Os níveis de triglicerídeos foram maiores no grupo DMO normal em comparação com o grupo osteoporótico (p = 0 005). O nível de VAI foi detectado como maior naquelas com DMO normal em comparação com as mulheres com osteoporose (p = 0 002). Além disso a análise de correlação mostrou uma correlação positiva entre a absorciometria de raios-X de dupla energia (DXA) nas pontuações T da coluna CC VAI e uma correlação negativa entre as pontuações T da coluna DXA e a idade. Conclusão Em nosso estudo encontramos níveis mais elevados de VAI naquelas com DMO normal em comparação com mulheres com osteoporose. Consideramos que novos estudos com maior tamanho amostral serão benéficos na elucidação da entidade.

Use of the SARC-F Score as an Aid in Fragility Fractures Prevention / O uso do escore SARC-F como auxiliar na prevenção de fraturas por fragilidade

Abstract Objective The present study aimed to relate the strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) score with the presence or absence of fragility fracture in the population over 60 years of age. Methods The risk of sarcopenia was determined through the application of the SARC-F questionnaire, and the patients were divided into 2 groups, according to the occurrence or not of fragility fracture (n = 100). Results Thirty-two cases of distal radius fractures and eighteen cases of proximal femur fractures were identified. A higher score on the SARC-F is determinant between having or not a fragility fracture, estimating that for each point in the score there is a 70% increase in the chance of a patient having a fracture, regardless of age, gender, and body mass index (BMI). Conclusion There was a direct correlation between a higher score on the SARC-F and an increase in the chance of fragility fracture.

Resumo Objetivo O presente estudo teve como objetivo relacionar o escore strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) com a presença ou não de fratura por fragilidade na população acima de 60 anos. Métodos O risco de sarcopenia foi determinado por meio da aplicação do questionário SARC-F, sendo os pacientes divididos em 2 grupos, de acordo com a ocorrência ou não de fratura por fragilidade (n = 100). Resultados Foram levantados 32 casos de fratura de rádio distal e 18 casos de fratura de fêmur proximal. Uma maior pontuação no SARC-F determina bem entre ter ou não ter fratura por fragilidade, estimando que a cada ponto a mais no escore há um acréscimo de 70% na chance de o paciente ter fratura, independentemente da idade, sexo e índice de massa corporal (IMC). Conclusão Houve correlação direta entre uma maior pontuação no SARC-F e aumento na chance de fratura por fragilidade.

Association of blood heavy metal levels with osteocalcin abnormality and incidence of osteoporosis in Saudi subjects / Associação de anormalidades de osteocalcina nos níveis de metais pesados no sangue e incidência de osteoporose em indivíduos sauditas

Abstract Serum toxic metals have been implicated in development of many diseases. This study investigated the association between blood levels of lead and cadmium with abnormal bone mineral density (BMD) and incidence of osteoporosis. Sixty Saudi male adults age matching were assigned into two groups: A healthy control group (n = 30) and osteoporosis patients diagnosed according to T-score (n = 30). Serum calcium, vitamin D, osteocalcin, lead, cadmium were measured. Osteoporotic group showed a highly significant elevation of blood lead and cadmium levels compared to the control group (p <0.001). BMD was negatively correlated with serum osteocalcin level compared with control. There was a significant negative correlation between the cadmium and lead levels (r=-0.465 and p-value = 0.01) and calcium (p < 0.004). Our findings suggested that high cadmium and lead were negative correlated to BMD and increased the risk factor for osteoporosis.

Resumo Os metais tóxicos do soro têm sido implicados no desenvolvimento de muitas doenças. Este estudo investigou a associação entre os níveis sanguíneos de chumbo e cádmio com densidade mineral óssea anormal (DMO) e incidência de osteoporose. Sessenta adultos sauditas do sexo masculino com idades iguais foram divididos em dois grupos: um grupo de controle saudável (n = 30) e pacientes com osteoporose diagnosticados de acordo com o T-score (n = 30). Cálcio sérico, vitamina D, osteocalcina, chumbo, cádmio foram medidos. O grupo osteoporótico apresentou elevação altamente significativa dos níveis de chumbo e cádmio no sangue em comparação ao grupo controle (p < 0,001). A DMO foi negativamente correlacionada com o nível de osteocalcina sérica em comparação com o controle. Houve correlação negativa significativa entre os níveis de cádmio e chumbo (r = -0,465 ep = 0,01) e cálcio (p < 0,004). Nossos achados sugeriram que cádmio e chumbo elevados foram correlacionados negativamente à DMO e aumentaram o fator de risco para osteoporose.

Guidelines for diagnosis and treatment of glucocorticoid-induced osteoporosis / 中华内科杂志

Glucocorticoid-induced osteoporosis (GIOP) is a skeletal disease characterized by decreased bone strength and increased fracture risk associated with long-term glucocorticoid use. GIOP is the most common secondary osteoporosis that critically affects the quality of life of patients. Currently, the incidence of GIOP in China remains high, with insufficient awareness and lack of prevention and treatment norms. Therefore, the Chinese Rheumatology Association has established this standard based on domestic and international experience, with the aim of raising awareness of prevention and treatment among clinicians, guiding the standardized diagnosis and treatment of this disease, and improving the overall prognosis of patients with GIOP.

Identification of core pathogenic genes and pathways in elderly osteoporosis based on bioinformatics analysis / 中华预防医学杂志

Objective: Using bioinformatics methods to analyze the core pathogenic genes and related pathways in elderly osteoporosis. Methods: From November 2020 and August 2021, eight elderly osteoporosis patients who received treatment and five healthy participants who underwent physical examinations in Beijing Jishuitan Hospital were selected as subjects. The expression level of RNA in the peripheral blood of eight elderly osteoporosis patients and five healthy participants was collected for high-throughput transcriptome sequencing and analysis. The gene ontology (GO) analysis Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed for the differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was constructed using the STRING website and Cytoscape software, and the most significant modules and hub genes were screened out. Results: Among the eight elderly osteoporosis patients, there were seven females and one male, with an average age of 72.4 years (SD=4.2). Among the five healthy participants, there were four females and one male, with an average age of 68.2 years (SD=5.7). A total of 1 635 DEGs (847 up-regulated and 788 down-regulated) were identified. GO analysis revealed that the molecular functions of DEGs were mainly enriched in structural constituents of the ribosome, protein dimerization activity, and cellular components were mainly enriched in the nucleosome, DNA packaging complex, cytosolic part, protein-DNA complex and the cytosolic ribosome. KEGG pathway analysis showed that DEGs were mainly enriched in systemic lupus erythematosus and ribosome. Gene UBA52, UBB, RPS27A, RPS15, RPS12, RPL13A, RPL23A, RPL10A, RPS25 and RPS6 were selected and seven of them could encode ribosome proteins. Conclusion: The pathogenesis of elderly osteoporosis may be associated with ribosome-related genes and pathways.

Adjuvant rice optimization of rice-steamed Rehmanniae Radix and its anti-osteoporosis effect / 中国中药杂志

The present study aimed to investigate the effect of various adjuvant rice on the quality of rice-steamed Rehmanniae Radix(RSRR) with Japonica rice, millet, yellow rice, black rice, and glutinous rice as raw materials, and analyze the anti-osteoporosis effect of RSRR by the optimal adjuvant rice. On the basis of the established UPLC-MS/MS method for the determination of the content of catalpol and rehmannioside D, comprehensive weighted scoring method was employed to evaluate the effect of various auxiliary rice on the quality of RSRR with the content of catalpol and rehmannioside D, character score, and taste score as indicators to optimize adjuvant rice. The osteoporosis model was induced by ovariectomy in rats. SD rats were randomly divided into a sham operation group, a model group, a positive control group, and low-dose and high-dose groups of Rehmanniae Radix, RSRR, steamed Rehmanniae Radix, and Epimedii Folium-RSRR. After treatment for 12 weeks, body weight, bone calcium content, and bone mineral density were mea-sured. The results showed that Japonica rice was selected as the optimal adjuvant due to the highest comprehensive score of RSRR steamed by Japonica rice. Rehmanniae Radix, RSRR, steamed Rehmanniae Radix, as well as Epimedii Folium-RSRR, could improve osteoporosis by increasing bone calcium content and bone mineral density. RSRR was superior to Rehmanniae Radix in improving osteo-porosis. However, there was no significant difference between RSRR and steamed Rehmanniae Radix. This study confirmed that Japo-nica rice was the optimal adjuvant rice of RSRR and verified the anti-osteoporosis effect of RSRR, which laid a foundation for further research on the pharmacological action and mechanism of RSRR.

Iron accumulation and its impact on osteoporotic fractures in postmenopausal women / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.

miR-877-3p causes osteoporosis in mice by inhibiting MCP-1 secretion from mouse bone marrow mesenchymal stem cells and the migration and apoptosis of T lymphocytes / 细胞与分子免疫学杂志

Objective To investigate the effects of miR-877-3p on migration and apoptotic T lymphocytes of bone mesenchymal stem cells (BMSCs). Methods The model of osteoporosis induced by bilateral ovariectomy (OVX) and sham operation was established. At 8 weeks after operation, the bone parameters of the two groups were detected by micro-CT. The levels of monocyte chemotactic protein 1(MCP-1) in BMSCs were detected by ELISA. BMSC in OVX group and sham group were co-cultured with T lymphocytes, respectively. The migration ability of T lymphocytes in the two groups was observed by TranswellTM assay with PKH26 staining and apoptosis of T lymphocytes were detected by flow cytometry. Reverse transcription PCR was used to detect the expression of miR-877-3p in BMSCs. miR-877-3p was overexpressed or down-regulated by cell transfection. The level of MCP-1 secreted by BMSCs in each group was detected by ELISA. The migration and apoptosis of T lymphocytes were detected by the above methods. Results The number of trabecular bone and bone mineral density in OVX group were lower than those in sham group. The levels of MCP-1 secretion, chemotactic and apoptotic T lymphocyte ability of BMSCs in OVX group were also lower than those in sham group. The expression level of miR-877-3p in BMSC in OVX group was higher than that in sham group. After overexpression of BMSC miR-877-3p, the levels of MCP-1 secreted from BMSCs, and apoptotic T lymphocytes decreased, while the results were opposite after down-regulation of miR-877-3p. Conclusion miR-877-3p may be one of the causes of osteoporosis by inhibiting MCP-1 secretion of BMSCs and the migration and apoptosis of T lymphocytes.

Advances on pentraxin 3 in osteoporosis and fracture healing / 中国骨伤

Pentaxin 3 (PTX3), as a multifunctional glycoprotein, plays an important role in regulating inflammatory response, promoting tissue repair, inducing ectopic calcification and maintaining bone homeostasis. The effect of PTX3 on bone mineral density (BMD) may be affected by many factors. In PTX3 knockout mice and osteoporosis (OP) patients, the deletion of PTX3 will lead to decrease of BMD. In Korean community "Dong-gu study", it was found that plasma PTX3 was negatively correlated with BMD of femoral neck in male elderly patients. In terms of bone related cells, PTX3 plays an important role in maintaining the phenotype and function of osteoblasts (OB) in OP state;for osteoclast (OC), PTX3 in inflammatory state could stimulate nuclear factor κ receptor activator of nuclear factor-κB ligand (RANKL) production and its combination with TNF-stimulated gene 6(TSG-6) could improve activity of osteoclasts and promote bone resorption;for mesenchymal stem cells (MSCs), PTX3 could promote osteogenic differentiation of MSCs through PI3K/Akt signaling pathway. In recent years, the role of PTX3 as a new bone metabolism regulator in OP and fracture healing has been gradually concerned by scholars. In OP patients, PTX3 regulates bone mass mainly by promoting bone regeneration. In the process of fracture healing, PTX3 promotes fracture healing by coordinating bone regeneration and bone resorption to maintain bone homeostasis. In view of the above biological characteristics, PTX3 is expected to become a new target for the diagnosis and treatment of OP and other age-related bone diseases and fracture healing.

Study on correlation between bone marrow edema and osteoporosis in patients with severe knee osteoarthritis / 中国骨伤

OBJECTIVE@#To explore relationship between bone marrow edema(BME) and osteoporosis in patients with severe knee osteoarthritis.@*METHODS@#Unmatched case-control study was conducted. Totally 160 patients with severe knee osteoarthritis who had undergone knee magnetic resonance imaging (MRI) and bone mineral density examination (BMD) from January 2020 to March 2021 were included. Eighty patients complicated with BME were included in BME group, and 80 patients without BME were selected as NBME group. In BME group, there were 12 males and 68 females, aged from 51 to 80 years old with an average of(66.58±8.10) years old;the courses of disease ranged from 5 to 40 months with an average of (15.61±9.25) months;body mass index(BMI) ranged from 21.81 to 34.70 with an average of (27.79±3.00) kg·m-2;25 patients classified to grade Ⅲ and 55 patients grade Ⅳ according to Kellgren- Lawrence(K-L). In NBME group, there were 15 males and 65 females, aged from 50 to 80 years old with an average of(67.82±8.05) years old;the course of disease ranged from 6 to 37 months with an average of(15.75±8.18) months;BMI ranged from 21.39 to 34.46 with an average of (28.26±3.13) kg·m-2;25 patients were K-L Ⅲ and 55 patients with K-L Ⅳ. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score(WORMS). Osteoporosis was diagnosed and BMD was evaluated by DXA T value. To explore the relationship between bone marrow edema and osteoporosis by comparing prevalence rate of osteoporosis between two groups, and to further explore relationship between BME and BMD by Spearman correlation analysis of BME WORMS score and DXA T value in BME group.@*RESULTS@#The complete case data were obtained on the first diagnosis, and there was no significant difference in sex, age, courses of disease and BMI between two groups (P>0.05). The proportion of K-L Ⅳ in BME group was significantly higher than that in NBME (P<0.05). The prevalence rate of osteoporosis in BME group was significantly higher than in NBME group with the same K-L grade (P<0.001), and there was a strong negative correlation between BME WORMS score and DXA BMD T value (r=-0.812, |r|=0.812 >0.8, P<0.001).@*CONCLUSION@#Osteoporosis is one of the risk factors of bone marrow edema in patients with severe knee osteoarthritis, and the lower the bone mineral density is, the easier it is to be complicated with bone marrow edema.

Regulatory function and mechanism of autophagy on osteoclast / 中国骨伤

Osteoclast (OC) is multinucleated, bone-resorbing cells originated from monocyte/macrophage lineage of cells, excessive production and abnormal activation of which could lead to many bone metabolic diseases, such as osteoporosis, osteoarthritis, etc. Autophagy, as a highly conserved catabolic process in eukaryotic cells, which plays an important role in maintaining cell homeostasis, stress damage repair, proliferation and differentiation. Recent studies have found that autophagy was also involved in the regulation of osteoclast generation and bone resorption. On the one hand, autophagy could be induced and activated by various factors in osteocalsts, such as nutrient deficiency, hypoxia, receptor activator of nuclear factor(NF)-κB ligand(RANKL), inflammatory factors, wear particles, microgravity environment, etc, different inducible factors, such as RANKL, inflammatory factors, wear particles, could interact with each other and work together. On the other hand, activated autophagy is involved in regulating various stages of osteoclast differentiation and maturation, autophagy could promote proliferation of osteoclasts, inhibiting apoptosis, and promoting differentiation, migration and bone resorption of osteoclast. The classical autophagy signaling pathway mediated by mammalian target of rapamycin complex 1(mTORC1) is currently a focus of research, and it could be regulated by upstream signalings such as phosphatidylinositol 3 kinase(PI-3K)/protein kinase B (PKB), AMP-activated protein kinase(AMPK). However, the paper found that mTORC1-mediated autophagy may play a bidirectional role in regulating differentiation and function of osteoclasts, and its underlying mechanism needs to be further ciarified. Integrin αvβ3 and Rab protein families are important targets for autophagy to play a role in osteoclast migration and bone resorption, respectively. In view of important role of osteoclast in the occurrence of various bone diseases, it is of great significance to elucidate the role of autophagy on osteoclast and its mechanism for the treatment of various bone diseases. The autophagy pathway could be used as a new therapeutic target for the treatment of clinical bone diseases such as osteoporosis.