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.

Periodontitis and osteoporosis: a two-sample Mendelian randomization analysis

Abstract The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.

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.

Integrative analyses of genetic characteristics associated with skeletal endothelial cells

Abstract The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.

Ozone therapy improves early stages of osseointegration in ovariectomized rats

Abstract Objective the aim of this study was to analyze the influence of ozone therapy (OZN) on peri-implant bone repair in critical bones by installing osseointegrated implants in the tibia of ovariectomized rats. Methodology ovariectomy was performed on 30 Wistar rats, aged six months (Rattus novergicus), and, after 90 days, osseointegrated implants were installed in each tibial metaphysis. The study groups were divided into the animals that received intraperitoneal ozone at a concentration of 700 mcg/kg — OZ Group (n=15) — and a control group that received an intraperitoneal saline solution and, for this reason, was named the SAL group (n=15). The applications for both groups occurred during the immediate post-operative period on the 2nd, 4th, 6th, 8th, 10th, and 12th day post-surgery. At various stages (14, 42, and 60 days), the animals were euthanized, and tests were performed on their tibiae. These tests include histomorphometric and immunohistochemical analyses, computerized microtomography, sampling in light-cured resin for calcified sections, and confocal microscopy. The obtained data were then analyzed using One-way ANOVA and the Shapiro-Wilk, Kruskal-Wallis, and student t-tests (P<0.05). Results our findings indicate that the OZ group (3.26±0.20 mm) showed better cellular organization and bone neoformation at 14 days (SAL group, 0.90±1.42 mm) (P=0.001). Immunohistochemistry revealed that osteocalcin labeling was moderate in the OZ group and mild in the SAL group at 14 and 42 days post-surgery. The data from the analysis of calcified tissues (microtomography, histometric, and bone dynamism analysis) at 60 days showed no statistically significant differences between the groups (P=0.32). Conclusion it was concluded that ozone therapy anticipated the initial phases of the peri-implant bone repair process.

Long-term consequences of osteoporosis therapy with bisphosphonates

ABSTRACT Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.

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

ABSTRACT 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)-β, 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-β and IGF. We concluded that bryodulcosigenin is an antiosteoporosis medication based on the findings.

Valoración de la densidad mineral ósea en personas transgénero posicionamiento de la Sociedad Argentina de Osteoporosis / Evaluation of bone health in transgender people. Position of the Argentine Osteoporosis Society

Resumen La Sociedad Argentina de Osteoporosis convocó a especialistas reconocidos en la atención de personas transgénero para la elaboración del primer posiciona miento local sobre la evaluación de la salud ósea en esta población. La ley 26.743 de "Identidad de género" reco noce todas las identidades y garantiza su atención de manera gratuita en el sistema de salud. El impacto de los diferentes tratamientos de afirmación de género sobre la masa ósea ha sido tópico de debate internacional. Hasta la fecha la evidencia sigue siendo limitada y diferentes sociedades han emitido sugerencias y recomendaciones. Por tal motivo, creemos relevante mencionar nuestra experiencia plasmando mediante este documento una serie de sugerencias para ser utilizadas en la atención médica.

Abstract The Argentine Osteoporosis Society convened renowned specialists in the care of transgender people to prepare the first local position on the evaluation of bone health in this population. Law 26.743 on "Gender Identity" recognize all identities and guarantees free care throughout the health system. The impact of different gender affirmation treatments on bone mass has been topic of international debate. To date the evidence remains limited and different societies have issued suggestions and recommendations. For this reason, we believe it is relevant to mention our experience, capturing through this document a series of suggestions to be used in medical care.

Accuracy of an artificial intelligence algorithm for detecting moderate-to-severe vertebral compression fractures on abdominal and thoracic computed tomography scans / Acurácia de um algoritmo de inteligência artificial na detecção de fraturas compressivas moderadas a graves na tomografia computadorizada abdominal e torácica

Abstract Objective: To describe the accuracy of HealthVCF, a software product that uses artificial intelligence, in the detection of incidental moderate-to-severe vertebral compression fractures (VCFs) on chest and abdominal computed tomography scans. Materials and Methods: We included a consecutive sample of 899 chest and abdominal computed tomography scans of patients 51-99 years of age. Scans were retrospectively evaluated by the software and by two specialists in musculoskeletal imaging for the presence of VCFs with vertebral body height loss > 25%. We compared the software analysis with that of a general radiologist, using the evaluation of the two specialists as the reference. Results: The software showed a diagnostic accuracy of 89.6% (95% CI: 87.4-91.5%) for moderate-to-severe VCFs, with a sensitivity of 73.8%, a specificity of 92.7%, and a negative predictive value of 94.8%. Among the 145 positive scans detected by the software, the general radiologist failed to report the fractures in 62 (42.8%), and the algorithm detected additional fractures in 38 of those scans. Conclusion: The software has good accuracy for the detection of moderate-to-severe VCFs, with high specificity, and can increase the opportunistic detection rate of VCFs by radiologists who do not specialize in musculoskeletal imaging.

Resumo Objetivo: Descrever a acurácia do software HealthVCF na detecção incidental de fraturas compressivas de corpos vertebrais moderadas a graves em exames de tomografia computadorizada do tórax e abdome. Materiais e Métodos: Foram incluídos 899 exames consecutivos de pacientes com idades entre 51 e 99 anos. As imagens foram retrospectivamente avaliadas pelo software e por dois radiologistas especializados em musculoesquelético que investigaram fraturas compressivas de corpos vertebrais com perda da altura somática > 25%. A análise comparativa foi realizada entre o software e um radiologista geral, usando a avaliação do especialista como referência. Resultados: O software apresentou uma acurácia de 89,6% (IC 95%: 87,4-91,5%) para fraturas compressivas moderadas a graves, com sensibilidade de 73,8%, especificidade de 92,7% e valor preditivo negativo de 94,8%. Entre as 145 tomografias positivas detectadas pelo software, o radiologista geral deixou de relatar as fraturas em 62 (42,8%) e o algoritmo detectou fraturas adicionais em 38 dessas tomografias. Conclusão: O software possui boa acurácia na detecção de fraturas compressivas moderadas a graves, com alta especificidade, podendo aumentar a taxa de detecção oportunística dessas fraturas por radiologistas não especializados em musculoesquelético.

Association between hepatitis A seropositivity and bone mineral density in adolescents and adults: a cross-sectional study using NHANES data

ABSTRACT BACKGROUND: Osteoporosis, characterized by decreased bone density and increased fracture risk, imposes significant physical, psychosocial, and financial burdens. Early detection and prevention are crucial for managing osteoporosis and reducing the risk of fractures. OBJECTIVES: To investigate the relationship between Hepatitis A seropositivity and bone mineral density (BMD) in adolescents and adults and to explore the potential link between Hepatitis A infection and osteoporosis risk. DESIGN AND SETTING: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 to evaluate the association between hepatitis A seropositivity and BMD in 15,693 participants. METHODS: Multivariable regression analysis was used to calculate the mean BMD and standard error for adolescents and adults, followed by an independent z-test to determine whether there was a significant difference between the seropositive and seronegative groups. RESULTS: Hepatitis A seropositive adolescents and adults had lower BMD than their seronegative counterparts, with significant differences in lumber spine (mean difference = -0.03 g/cm2, P < 0.01 for both age groups) and pelvis BMDs (mean difference = -0.02 g/cm2, P < 0.01 for the adult age groups), after adjusting for various covariates. CONCLUSIONS: This study confirmed that both adolescent and adult individuals seropositive for Hepatitis A antibodies had reduced BMD among both adolescents and adults, especially in the adult group. This finding suggests a possible link between Hepatitis A infection and risk of osteoporosis.

Meta-analysis of Distribution Frequency of Traditional Chinese Medicine Syndrome in Primary Osteoporosis / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the distribution of traditional Chinese medicine（TCM） syndromes of primary osteoporosis（POP） in China by using evidence-based medicine methods， and to understand the distribution law of the syndromes. MethodChina National Knowledge Infrastructure（CNKI）， VIP Chinese Science and Technology Journal Database（VIP）， WanFang Data Knowledge Service Platform（WanFang） and China Biology Medicine（CBM） were searched to obtain representative literature， and each database was searched from the 1994 World Health Organization defined diagnostic criteria for osteoporosis until May 1， 2023. Two researchers independently screened literature according to the criteria， extracted data， and cross-checked them. Meta analysis was conducted using R4.1.3， and subgroup analysis was performed. ResultA total of 56 Chinese papers were included， involving 14 415 patients. After standardized classification of syndromes， 11 articles were excluded， and Meta analysis results of the ultimately included 45 Chinese articles showed that the distribution frequencies of liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome in 12 723 patients were 27%［95% confidence interval（CI） 0.24-0.31］， 32%（95% CI 0.29-0.36）， 36%（95% CI 0.30-0.42）. Subgroup analysis showed that there was a statistically significant difference in the distribution of the three TCM syndromes in the north and south（P<0.05）. In addition， the incidence of TCM syndrome fractures in different types of POP was 15%（95% CI 0.09-0.24） for liver-kidney Yin deficiency syndrome， 20%（95% CI 0.12-0.30） for spleen-kidney Yang deficiency syndrome， and 31%（95% CI 0.25-0.39） for kidney deficiency and blood stasis syndrome. ConclusionThe distribution of syndromes in POP patients is mainly kidney deficiency， accompanied by liver and spleen dysfunction. Liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome are all the main syndromes of POP and osteoporotic fractures， and kidney deficiency and blood stasis syndrome is most closely related to the development of osteoporotic fractures. The reference standards for syndrome determination among the included studies are inconsistent， and in the future， it is necessary to focus on their determination standards to obtain consensus research results， at the same time， conduct large-scale syndrome research to obtain representative research results， providing a basis for clinical practice and research.

Effect and Mechanism of Chinese Medicine in Treatment of Osteoporosis / 中国实验方剂学杂志

Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.

Mechanism of Youguiwan Regulating BMP-2/Smad Signaling Pathway to Promote Bone Formation in Postmenopausal Rats with Osteoporosis / 中国实验方剂学杂志

ObjectiveTo observe the effects of Youguiwan on bone metabolism and bone morphogenetic protein-2 （BMP-2）/Smad signaling pathway in ovaries-removed rats with osteoporosis and study the mechanism of Youguiwan in the prevention and treatment of osteoporosis. MethodA postmenopausal rat model of osteoporosis was prepared by bilateral ovariectomy. The 40 female SD rats were randomly divided into five groups， including sham operation group， model group， alendronate sodium group （0.1 mg·kg-1）， and high-dose and low-dose （5.36 and 2.68 g·kg-1） groups of Youguiwan. The drug was given seven days after modeling， once a day for 12 weeks. After the treatment， the changes in femur tissue structure were observed by micro-CT， including bone mineral density （BMD）， bone volume/total volume （BV/TV）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， bone surface/bone volume （BS/BV）， and trabecular separation （Tb.Sp）. Ossification was observed by saffrane-solid green staining， and serum levels of bone metabolism markers， including bone alkaline phosphatase （BALP）， osteocalcin （BGP）， type Ⅰ procollagen amino terminal propeptide （PINP）， and tartrate-resistant acid phosphatase 5b （TRACP-5b）， were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression levels of Runx2， BMP-2， and Smad1 in rat femur were detected by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the sham operation group， bone trabecula in the model group was sparse. BMD， BV/TV， Tb.N， and Tb.Th were decreased （P<0.05， P<0.01）. BS/BV （P<0.05） and Tb.Sp were increased. The content of BGP， BALP， PINP， and TRACP-5b in serum was significantly increased （P<0.01）. The mRNA and protein expressions of Runx2， BMP-2， and Smad1 in rat femur were significantly decreased （P<0.05， P<0.01）. Compared with the model group， the number of bone trabeculae in the high-dose and low-dose groups of Youguiwan was increased， and the bone microstructure was improved. BMD， BV/TV， Tb.N， and Tb.Th were increased significantly （P<0.05， P<0.01）， and BS/BV and Tb.Sp were increased. The content of bone metabolic markers decreased （P<0.05， P<0.01）. ConclusionYouguiwan has certain preventive and therapeutic effects on postmenopausal osteoporosis， and its mechanism may be related to promoting bone formation by regulating the BMP-2/Smad signaling pathway.

Effect of Osteoking on Inflammatory Injury and NF-κB/NFATc1 Signaling Pathway in Model Mice with Postmenopausal Osteoporosis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of Osteoking （OK） on postmenopausal osteoporosis （PMOP）. MethodForty adult female mice were randomly divided into a sham operation （Sham） group， osteoporosis model （OVX） group， estradiol intervention （E2） group， and OK group， with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy， and the corresponding drugs were given one week later. After 12 weeks， the body mass and uterine index of mice were measured， and the pathological changes of bone tissue and the number of osteoclasts （OCs） were determined by hematoxylin-eosin （HE） and tartrate-resistant acid phosphatase （TRAP） staining， respectively. Bone mineral density （BMD）， trabecular number （Tb.N）， trabecular separation （Tb.Sp）， and bone volume fraction （BV/TV） were measured by microcomputed tomography （Micro-CT）. The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α （TNF-α） and bone resorption marker C-terminal telopeptide of type Ⅰ collagen （CTX-1） were measured by enzyme linked immunosorbent assay （ELISA）. The protein expression levels of nuclear factor-kappa B p65 （NF-κB p65）， phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65）， nuclear factor kappa B inhibitor alpha （IκBα）， phosphorylated nuclear factor kappa B alpha （p-IκBα）， nuclear factor of activated T cells 1 （NFATc1）， and proto-oncogene （c-Fos） were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 （MMP-9）， NFATc1， TRAP， cathepsin K （CTSK）， and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the Sham group， the uterine index decreased significantly in the OVX group， and the body mass （BMI） increased significantly. The structure of bone trabeculae was completely damaged， and the number of OCs increased. BMD， Tb.N， BV/TV， and maximum load decreased， while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were up-regulated （P<0.05， P<0.01）. Compared with the OVX group， the body mass of the OK and E2 groups decreased， and the uterine index increased. The bone trabeculae increased， and the number of OCs decreased. BMD， Tb.N， BV/TV， and maximum load increased， while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were decreased， and the mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were decreased （P<0.05， P<0.01）. ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice， which is one of the mechanisms for treating PMOP.

Morin Mediates Protective Effects on Bone in Aged Rats by Inhibiting ERK1/2-p38 Signaling Pathway / 中山大学学报(医学科学版)

ObjectiveTo investigate the effects of morin treatment on bone metabolism and bone mass in aged rats， and to clarify the possible mechanism. MethodsTen young female Sprague-Dawley rats （3 months old） and 20 old female Sprague-Dawley rats （24 months old） were randomly divided into three groups： Control group （CON， 10 young rats）； Model group （MOD， 10 young rats）； 10 old rats and SangHuangSu Group （SSS， 10 old rats）. During the experiment， the SSS group received intraperitoneal injection of morin （10 mg / kg） daily. The treatment lasted for 12 weeks. After treatment， Micro-CT， HE stained sections， serological tests and Western blot were used to observe the treatment effect and possible mechanism. ResultsAfter 12 weeks of treatment， compared with MOD group， the number and density of bone trabeculae in SSS group were significantly improved. The BMD， Conn. D， Tb. N， Tb.Th and Tb.Sp of the left femur in the SSS group were significantly better than those in the MOD group（P <0.05）. After 12 weeks of treatment， the levels of CTX-1， osteocalcin， TRACP-5b and PINP in SSS group were significantly lower than those in MOD group（P <0.05）. Compared with the MOD group， the ERK1/2-p38 signal pathway was significantly inhibited and the levels of ERK1/2 and p38 were significantly decreased in the SSS group（P <0.05）. ConclusionMorin pigment mediates the protective effect on the bones of aged rats by inhibiting the ERK1/2-p38 signaling pathway and reducing bone turnover.

Risk analysis of re⁃fracture after percutaneous kyphoplasty in elderly patients with osteoporotic thoracolumbar compression fractures and construction of a columnar graph prediction model / 解剖学报

Objective To investigate the risk factors for re-fracture after percutaneous kyphoplasty (PKP) in elderly patients with osteoporotic thoracolumbar compression fractures and to construct a line graph prediction model. Methods One hundred and eighty-two elderly patients with osteoporotic thoracolumbar compression fractures treated with PKP from January 2016 to November 2019 were selected for the study‚ and the patients were continuously followed up for 3 years after surgery. Clinical data were collected from both groups; Receiver operating characteristic (ROC) curve analysis was performed on the measures; Logistic regression analysis was performed to determine the independent risk factors affecting postoperative re-fracture in PKP; the R language software 4. 0 “rms” package was used to construct a predictive model for the line graph‚ and the calibration and decision curves were used to internally validate the predictive model for the line graph and for clinical evaluation of predictive performance. Results The differences between the two groups were statistically significant (P0. 22‚ which could provide a net clinical benefit‚ and the net clinical benefit was higher than the independent predictors. Conclusion BMD‚ number of injured vertebrae‚ single-segment cement injection‚ cement leakage‚ pre-and post-PKP vertebral height difference‚ and posterior convexity angle change are independent risk factors affecting the recurrent fracture after PKP in elderly patients with osteoporotic thoracolumbar compression fracture‚ and this study constructs a column line graph model to predict the recurrent fracture after PKP in elderly patients with osteoporotic thoracolumbar compression fracture as a predictor for clinical. This study provides an important reference for clinical prevention and treatment‚ and has clinical application value.

Curcumin plays an anti-osteoporosis role by inhibiting NF-κB signaling pathway to reduce oxidative stress damage to osteogenesis / 中国药理学通报

Aim To investigate the mechanism of curcumin inhibition of oxidative stress on osteogenic differentiation and its dose-dependent anti-osteoporosis effect. Methods Cellular oxidative stress models were used, different concentrations of curcumin were added to determinethebone formation markers, and the potential signaling pathways involvedwere detected. Meanwhile, the mouse model of osteoporosis ( ovariecto- mized, 0VX) was used to confirm its effect against osteoporosis. Results In vitro experiments found that low concentrations of curcumin (1-10 μmol · L

Research progress on bone metabolism and molecular mechanisms in accelerated aging SAMP6 mice / 中国药理学通报

Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. The pathogenesis of SOP is complex and not well understood. Currently, the rapid aging model mouse, senescence accelerated mouse prone 6 (SAMP6), is an ideal model for studying the mechanisms of SOP development and exploring its prevention and treatment. This model exhibits characteristics including increased bone fragility, degradation of bone microstructure, loss of bone matrix, and abnormal metabolism and dysfunction of bone cells, faithfully replicating the process of SOP occurrence and progression at both macroscopic and microscopic levels.

Mechanism of Wen Shen Xuan Bi Tang in treatment of osteoporosis based on network pharmacology and animal experimental verification / 中国药理学通报

Aim To predict and validate the mechanism of wenshen xuanbi tang(WSXBT) in treatment of osteoporosis (OP) based on network pharmacology, molecular docking techniques and in vivo experimental techniques. Methods Network pharmacology was used to screen the key ingredients and core targets of WSXBT for the treatment of osteoporosis. Metascape database was used for gene ontology (GO) biological process enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis of core targets. AutoDockTools 1. 5. 7 software was applied in molecular docking to simulate the binding activity of key active ingredients to core targets. To study the efficacy of WSXBT on rats with osteoporosis and to verify the related targets and pathways, rat models of osteoporosis were established by excising the bilateral ovaries of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum OPG, PINP and RANKL content. Biomechanical tester was applied to test the biomechanics of rat femurs. Micro-CT was applied to detect the femoral bone density. Then, Western blot was employed to measure the protein expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt). Results A total of 156 active ingredients of WSXBT were screened, involving 229 potential targets, 23 core targets and 145 signaling pathways. The molecular docking results showed that five key ingredients, including quercetin, kaempferol, naringenin, isobavachin and licochalcone a, possessed good binding ability to the core targets of PIK3R1 and AKT1. The results of in vivo experiments showed that WSXBT could significantly increase bone density, improve bone tissue microstructure, enhance femur biomechanics and increase PINP expression and OPG/RANKL ratio in rats with osteoporosis. Results of WB showed that WSXBT significantly increased p-PI3K/PI3K and p-Akt/Akt ratios. Conclusions WSXBT could improve bone mineral density in postmenopausal osteoporotic rats through PI3K/ Akt signaling pathway and increasing OPG/RANKL ratio.

Role of Wnt signaling Pathway in Diabetic Osteoporosis and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Diabetic osteoporosis （DOP） is a kind of bone complication caused by diabetes， which is characterized by the decrease of bone mineral density， the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose， insulin resistance， oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β（GSK-3β）phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling， which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis， but also promotes the expression of osteopontin， osteocalcin and type Ⅰ collagen， and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years， the research of traditional Chinese medicine （TCM） in the prevention and treatment of DOP has gradually increased， and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism， bone metabolism and DOP worldwide in the past decade， as well as the related literature on the intervention of DOP by TCM compounds （classical and other compounds）， single Chinese medicine and TCM monomers based on the Wnt pathway， in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.