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.

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.

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.

Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion / 中国骨伤

OBJECTIVE@#To observe the cage subsidence after oblique lateral interbody fusion (OLIF) for lumbar spondylosis, summarize the characteristics of the cage subsidence, analyze causes, and propose preventive measures.@*METHODS@#The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively analyzed. There were 43 males and 101 females, and the age ranged from 20 to 81 years old, with an average of (60.90±10.06) years old. Disease types:17 patients of lumbar intervertebral disc degenerative disease, 12 patients of giant lumbar disc herniation, 5 patients of discogenic low back pain, 33 patients of lumbar spinal stenosis, 26 patients of lumbar degenerative spondylolisthesis, 28 patients of lumbar spondylolisthesis with spondylolisthesis, 11 patients of adjacent vertebral disease after lumbar internal fixation, 7 patients of primary spondylitis in the inflammatory outcome stage, and 5 patients of lumbar degenerative scoliosis. Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis, and 87 patients of normal bone density. The number of fusion segments:124 patients of single-segment, 11 patients of two-segment, 8 patients of three-segment, four-segment 1 patient. There were 40 patients treated by stand-alone OLIF, and 104 patients by OLIF combined with posterior pedicle screw. Observed the occurrence of fusion cage settlement after operation, conducted monofactor analysis on possible risk factors, and observed the influence of fusion cage settlement on clinical results.@*RESULTS@#All operations were successfully completed, the median operation time was 99 min, and the median intraoperative blood loss was 106 ml. Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients. The mean follow-up was (14.57±7.14) months from 6 to 30 months. During the follow-up, except for the patients of primary lumbar interstitial inflammation and some patients of lumbar spondylolisthesis with spondylolisthesis, the others all had different degrees of cage subsidence. Cage subsidence classification:119 patients were normal subsidence, and 25 patients were abnormal subsidence (23 patients were gradeⅠ, and 2 patients were gradeⅡ). There was no loosening or rupture of the pedicle screw system. The height of the intervertebral space recovered from the preoperative average (9.48±1.84) mm to the postoperative average (12.65±2.03) mm, and the average (10.51±1.81) mm at the last follow-up. There were statistical differences between postoperative and preoperative, and between the last follow-up and postoperative. The interbody fusion rate was 94.4%. The low back pain VAS decreased from the preoperative average (6.55±2.2 9) to the last follow-up (1.40±0.82), and there was statistically significant different. The leg pain VAS decreased from the preoperative average (4.72±1.49) to the final follow-up (0.60±0.03), and the difference was statistically significant (t=9.13, P<0.000 1). The ODI index recovered from the preoperative average (38.50±6.98)% to the latest follow-up (11.30±3.27)%, and there was statistically significant different. The complication rate was 31.3%(45/144), and the reoperation rate was 9.72%(14/144). Among them, 8 patients were reoperated due to fusion cage subsidence or displacement, accounting for 57.14%(8/14) of reoperation. The fusion cage subsidence in this group had obvious characteristics. The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group, Stand-alone OLIF group, 2 or more segments fusion group, and endplate injury group was higher than that in the normal bone mass group, OLIF combined with pedicle screw fixation group, single segment fusion group, and no endplate injury group, and the comparison had statistical differences.@*CONCLUSION@#Cage subsidence is a common phenomenon after OLIF surgery. Preoperative osteopenia or osteoporosis, Stand-alone OLIF, 2 or more segments of fusion and intraoperative endplate injury may be important factors for postoperative fusion cage subsidence. Although there is no significant correlation between the degree of cage subsidence and clinical symptoms, there is a risk of cage migration, and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence, including reoperation.

Treatment with Raloxifene Induces the Expression of Kisspeptin, Insulin, and Androgen Receptors in Bones of Castrated Adult Female Rats / Tratamento com raloxifeno induz à expressão dos receptores de kisspeptina, insulina e androgênio em ossos de ratas adultas castradas

Abstract Objective To evaluate the effects of estrogen, raloxifene and genistein on the expression of KISS1 (kisspeptin), KISS1R (kisspeptin receptor), AR (androgen receptor) and INSR (insulin receptor) in the bones of ovariectomized rats. Methods Forty-eight adult rats were randomly divided into 6 groups, containing 8 animals each: G1-nonovariectomized control; G2-ovariectomized and treated with conjugated equine estrogens (50 µg/Kg/day); G3-ovariectomized and treated with raloxifene (0.75 mg/kg/day); G4-ovariectomized animal that received soy extract with genistein (300 mg/kg/day); G5-ovariectomized animal that received estrogen and genistein; and G6-ovariectomized animal that received estrogen and raloxifene. Three months after surgery, the castrated animals received the drugs orally daily for 120 days. All animals were sacrificed after this period, by deepening the anesthesia. The left tibia was removed for total RNA extraction and analysis of gene expression of KISS1, KISS1R, AR and INSR, by quantitative real-time polymerase chain reaction (qRT-PCR). Results KISS1 was not detected in any of the treated groups. KISS1R, INSR and AR showed higher expression in the G3 group (p < 0.001), while lower levels of transcripts for these genes were observed in G4 and G5. G2 animals showed hypoexpression of the evaluated genes. Conclusion The results indicate that raloxifene, alone or combined with estrogen, was able to induce the expression of genes associated with the recovery of bone tissue homeostasis in ovariectomized rats.

Resumo Objetivo Avaliar os efeitos do estrogênio, raloxifeno e genisteína na expressão de KISS1 (kisspeptina), KISS1R (receptor da kisspeptina), AR (receptor de androgênio) e INSR (receptor de insulina) nos ossos de ratas ovariectomizadas. Métodos Quarenta e oito ratas adultas foram divididas aleatoriamente em 6 grupos, contendo 8 animais cada: G1-controle não ovariectomizado); G2-ovariectomizado e tratado com estrogênios conjugados equinos (50 µg/Kg/dia); G3-ovariectomizado e tratado com raloxifeno (0,75 mg/kg/dia); G4-ovariectomizado que recebeu extrato de soja com genisteína (300 mg/kg/dia); G5-ovariectomizado que recebeu estrogênio e genisteína; e G6-ovariectomizado que recebeu estrogênio e raloxifeno. Após 3 meses da cirurgia, os animais castrados receberam os fármacos diariamente por via oral, durante 120 dias. Todos os animais foram sacrificados após esse período, por aprofundamento da anestesia. A tíbia esquerda foi removida para extração de RNA total e análise da expressão gênica de KISS1, KISS1R, AR e INSR, por reação de cadeia de polimerase quantitativa em tempo real (quantitative real-time polymerase chain reaction, qRT-PCR, em inglês). Resultados KISS1 não foi detectado em nenhum dos grupos tratados. KISS1R, INSR e AR mostraram maior expressão no grupo G3 (p < 0,001), enquanto menores níveis de transcritos para esses genes foram observados em G4 e G5. Os animais de G2 apresentaram hipoexpressão dos genes avaliados. Conclusão Os resultados indicam que o raloxifeno, isolado ou combinado com estrogênio, foi capaz de induzir a expressão de genes associados à recuperação da homeostase do tecido ósseo em ratas ovariectomizadas.

Antiosteoporosis effect of bryodulcosigenin on ovariectomy-induced osteoporosis in experimental rats

Purpose: Osteoporosis is a bone disease which commonly occurred in postmenopausal women. Almost 10 percent of world population and approximately 30% of women (postmenopausal) suffer from this disease. Alternative medicine has great success in the treatment of osteoporosis disease. Bryodulcosigenin, a potent phytoconstituent, already displayed the anti-inflammatory and antioxidant effect. In this study, we made effort to analyze the antiosteoporosis effect of bryodulcosigenin against ovariectomy (OVX) induced osteoporosis in rats. Methods: Swiss albino Wistar rats were grouped into fIve groups and given an oral dose of bryodulcosigenin (10, 20 and 30 mg/kg) for eight weeks. Body weight, uterus, bone mineral density, cytokines, hormones parameters, transforming growth factor (TGF)-ß, insulin-like growth factor (IGF), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL), and its ratio were estimated. Results: Bryodulcosigenin significantly (p < 0.001) suppressed the body weight and enhanced the uterine weight and significantly (p < 0.001) increased the bone mineral density in whole femur, caput femoris, distal femur and proximal femur. Bryodulcosigenin significantly (P < 0.001) altered the level of biochemical parameters at dose dependent manner, significantly (P < 0.001) improved the level of estrogen and suppressed the level of follicle stimulating hormone and luteinizing hormone. Bryodulcosigenin significantly (P < 0.001) improved the level of OPG and suppressed the level of RANKL. Conclusions: Bryodulcosigenin reduced the cytokines level and suppressed the TGF-ß and IGF. We concluded that bryodulcosigenin is an antiosteoporosis medication based on the findings.

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.

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.

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.

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.

Mechanism of active components of "Notoginseng Radix et Rhizoma-Drynariae Rhizoma" in treatment of osteoporosis based on network pharmacology and in vitro cell experiment / 中国中药杂志

The present study aimed to explore the main active components and potential mechanisms of Panax notoginseng saponins(PNS) and osteopractic total flavone(OTF) in the treatment of osteoporosis(OP) through network pharmacology, molecular docking and in vitro cell experiments, which was expected to provide a theoretical basis for clinical applications. The blood-entering components of PNS and OTF were obtained from literature search and online database, and their potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The OP targets were obtained by means of searching Online Mendelian Inheritance in Man(OMIM) and GeneCards. The common targets of the drug and disease were screened by Venn. Cytoscape was used to construct a "drug-component-target-disease" network, and the core components were screened according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened according to the node degree. GO and KEGG enrichment analysis of potential therapeutic targets were carried out by R language. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock Vina. Finally, HIF-1 signaling pathway was selected for in vitro experimental verification according to the results of KEGG pathway analysis. Network pharmacology showed that there were 45 active components such as leachianone A, kurarinone, 20(R)-protopanaxatriol, 20(S)-protopanaxatriol, and kaempferol, and 103 therapeutic targets such as IL6, AKT1, TNF, VEGFA and MAPK3 involved. PI3K-AKT, HIF-1, TNF and other signaling pathways were enriched. Molecular docking revealed that the core components had good binding ability to the core targets. In vitro experiments found that PNS-OTF could up-regulate the mRNA expression levels of HIF-1α, VEGFA and Runx2, indicating that the mechanism of PNS-OTF in treating OP may be related to the activation of HIF-1 signaling pathway, and thus PNS-OTF played a role in promoting angiogenesis and osteogenic differentiation. In conclusion, this study predicted the core targets and pathways of PNS-OTF in treating OP based on network pharmacology and carried out in vitro experimental verification, which reflected the characteristics of multi-component, multi-target and multi-pathway synergy of PNS-OTF, and provided new ideas for the future clinical treatment of OP.

A study on the Charlson comorbidity index and health-related quality of life in the middle-aged and elderly osteoporosis population / 中国骨伤

OBJECTIVE@#To explore the characteristics of comorbidities in patients with osteoporosis(OP) and factors associated health-related quality of life, so as to provide decision-making reference for improving the ability of disease co-prevention and co-treatment and the patient's life-cycle quality of life.@*METHODS@#From November 2017 to July 2018, clinical information and biological samples from residents in 10 communities in Chaoyang District and Fengtai Distric of Beijing were collected, and bone density testing was conducted. Based on the Charlson comorbidity index (CCI), the comorbidity of the population was quantified, and grouped according to factors such as gender, age, and the differences between the groups were explored. Combined with the clinical information of patients, the difference characteristics of comorbidity and non-comorbidity population were analyzed. Pearson/Spearman correlation analysis and binary Logistic regression analysis were used to explore the factors affecting the health-related quality of life in patients with OP.@*RESULTS@#Among the 521 OP patients, 121 patients had no comorbidities, and there were 153, 106, 65, and 30 patients with one, two, three, and four comorbidities, respectively, 46 patients with 5 or more kinds of comorbidites. Hypertension was the most common comorbidity in OP patients, accounting for 21.60%;followed by hyperlipidemia, accounting for 13.51%. The most common combination of the two diseases was hypertension plus hyperlipidemia (64 cases, 12.28%). Through the analysis of differences between age groups, it was found that the older patients, showed higher the CCI, and the difference between groups was statistically significant(Z=1.93, P=0.05). There were significant differences in the total EQ-5D score and the dimensions of anxiety and depression between patients with comorbidities (CCI≠0) and non-comorbidities (CCI=0) (Z=-2.67, P=0.01;Z=-2.44, P=0.02). Correlation analysis found that CCI, history of fracture, history of falls, hip bone mineral density T value and parathyroid hormone were all related to the health-related quality of life in OP patients (P<0.05). Binary Logistic regression analysis suggested that the right hip bone mineral density T value (P=0.02), CCI (P=0.01), fracture history (P=0.03) and fall history (P=0.01) were the risk factors that affect the health-related quality of life in OP patients.@*CONCLUSION@#The burden of comorbidities among middle-aged and elderly OP populations in Beijing is relatively heavy, and the health management of such populations should be further strengthened, specifically the combination of multiple comorbidities should be given high priority. Comorbid factors are of great importance for the diagnosis and treatment strategy of OP patients, which could further improve the quality of life.

Resveratrol Modulates Bone Mineral Density and Bone Mineral Content in A Rat Model of Male Hypogonadism / 中国结合医学杂志

OBJECTIVE@#To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism.@*METHODS@#Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed.@*RESULTS@#ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05).@*CONCLUSION@#Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.

Telecarers improve osteoporosis treatment and compliance rates in secondary osteoporosis prevention for elderly hip fracture patients

INTRODUCTION@#A significant treatment gap has been observed in patients with osteoporosis. Our previous audit found a 31.5% rate of anti-osteoporosis medication initiation after fragility fractures at one year. We piloted the use of telecarers to monitor osteoporosis treatment and compliance.@*METHODS@#From January 2017 to January 2018, all hip fracture patients at Changi General Hospital, Singapore, were automatically enrolled into the Health Management Unit valued care hip fracture programme. Telecarer calls were scheduled at discharge, 3, 6 and 12 months. We assessed the acceptability, completion and treatment rates of patients enrolled in this programme.@*RESULTS@#A total of 537 patients with a hip fracture were enrolled in the telecarer programme over one year. Their average age was 79.8 ± 8.23 years, and 63.1% of them were female. A total of 341 patients completed 12 months of follow-up, of which 251 (73.6%) patients were on treatment at 12 months. The most common cause of lack of initiation of secondary osteoporosis treatment was patient or family rejection (34.4%), followed by physician failure to prescribe (24.4%) and renal impairment (24.4%). 16.7% of patients were deemed to have advanced dementia with a life-limiting illness and were, thus, deemed unsuitable for treatment.@*CONCLUSION@#Telecarers may be a useful adjunct in the monitoring of osteoporosis treatment after hip fractures in an elderly population. The main limitations are patient or family rejection and physician inertia. Further studies should focus on a combination of interventions for both patients and physicians to increase awareness of secondary fracture prevention.

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.