Systemic Skeletal Disease Research Articles

Effects of Melandriumfirmum Rohrbach on RANKL‑induced osteoclast differentiation and OVX rats.

Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density (BMD), which results in an increased risk of fracture. Melandrium firmum (Siebold & Zucc.) Rohrbach (MFR), ‘Wangbulryuhaeng’ in Korean, is the dried aerial portion of Melandrii Herba Rohrbach, which is a member of the Caryophyllaceae family and has been used to treat several gynecological conditions as a traditional medicine. However, to the best of our knowledge, the effect of MFR on osteoclast differentiation and osteoporosis has not been assessed. To evaluate the effects of MFR on osteoclast differentiation, tartrate-resistant acid phosphatase staining, actin ring formation and bone resorption assays were used. Additionally, receptor activator of nuclear factor-κB ligand-induced expression of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) and c-Fos were measured using western blotting and reverse transcription-PCR. The expression levels of osteoclast-related genes were also examined. To further investigate the anti-osteoporotic effects of MFR in vivo, an ovariectomized (OVX) rat model of menopausal osteoporosis was established. Subsequently, the femoral head was scanned using micro-computed tomography. The results revealed that MFR suppressed osteoclast differentiation, formation and function. Specifically, MFR reduced the expression levels of osteoclast-related genes by downregulating transcription factors, such as NFATc1 and c-Fos. Consistent with the in vitro results, administration of MFR water extract to OVX rats reduced BMD loss, and reduced the expression levels of NFATc1 and cathepsin K in the femoral head. In conclusion, MFR may contribute to alleviate osteoporosis-like symptoms. These results suggested that MFR may exhibit potential for the prevention and treatment of postmenopausal osteoporosis.

Mesenchyme homeobox 1 mediated-promotion of osteoblastic differentiation is negatively regulated by mir-3064-5p

Human mesenchymal stem cells (hMSCs) are multipotent cells that can be differentiated into different cell types including osteoblasts. Herein we aimed to assess the regulation of transcription factor mesenchyme homeobox 1 (Meox1) in the osteogenic differentiation of hMSCs and to determine the microRNA which targets on Meox1. Total RNA was extracted from the isolated ligamentum flavum tissue samples and cultured hMSCs, and the expression of Meox1 was assessed by RT-PCR and Western blot assays. Cultured hMSCs were induced towards osteoblastic differentiation, and the osteoblast phenotype was determined by alkaline phosphatase activity and alizarin red staining. The microRNA targeting on the 3′-UTR of Meox1was predicted using bioinformatics tool, and the binding was validated by luciferase and RNA pulldown assays. The osteoblastic differentiation of hMSCs was checked with the knockdown of Meox1 and microRNA inhibitors. Higher expression of Meox1, and lower expression of miR-3064–5p in ossified ligamentum flavum (OLF) tissues were identified. In addition, increased expression along with the osteoblastic differentiation of hMSCs was found. Further research revealed that Meox was a direct target of miR-3064–5p, when the former promoted the differentiation of hMSCs into osteoblasts, the latter significantly suppressed the osteogenesis. The expression of Meox1 increased gradually with the osteoblastic differentiation of hMSCs, during which miR-3064–5p decreased. Meox1 is a direct target of miR-3064–5p, and they both play important roles in the osteogenesis. These findings provide potential target for the development of therapeutic drugs for skeletal system diseases.

DXA reference values of the humanoid sheep model in preclinical studies.

BackgroundMerino land sheep are a popular pre-clinical large animal model in research on systemic skeletal diseases such as osteoporosis. Interpretation of studies is difficult because many reference parameters are missing or not established. This study aims to determine the reference parameters of the skeletal system (peak bone mass = PBM, T-Score). A defined standard allows an easier comparison of the study data of the animal model with human studies (T-Score).Materials and methodsA total of 116 Dual Energy X-ray Absorptiometry DXA measurements were performed on 74 untreated sheep. The average age of the animals was 57 months. The BMD, BMC, and fat content of the sheep were determined by the relevant human region of interest (ROI). From this, the PBM and from this the T-score for each of the animals were calculated.ResultsUsing 682 DXA measurements BMD and BMC were determined to provide an indication to PBM. For BMD a significant correlation to the age of the animals was observed (p = 0.043). A significant correlation was also seen for BMC (B) (p ≤ 0.001). In the age-dependent analysis, a widespread of values above the linear regression line was measured for both BMD and BMC between the 50th and 90th months of life. From an age of about 90 months, a wider spread of values below the linear regression line was found, although the average values continued to rise.DiscussionThe evaluation of the 116 DXA measurements allowed the determination of the PBM for merino land sheep. With the help of the PBM, a T-score was calculated for each animal. The statistical analysis shows significant differences in BMD values between the different animal groups in each of the four ROIs investigated. Individual control or sham groups per study are therefore not sufficient. To improve comparability, an independent reference group should be established.ConclusionAn independent reference group for PBM and a T-score was established from four to six-year-old animals. The bone density increases with the age of the animals. Around the fourth year of life, a first peak could be observed. Also, after the seventh year of life, a further peak with the beginning plateau phase was observed. When compiling a group of animals for an osteoporosis model, animals from the age of seven years should, therefore, be used.

Timing, Dosage, and Adherence of Antiretroviral Therapy and Risk of Osteoporosis in Patients With Human Immunodeficiency Virus Infection in Taiwan: A Nested Case-Control Study.

The progression of acquired immunodeficiency syndrome is delayed in patients with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy (ART). However, long-term ART is associated with adverse effects. Osteoporosis is one of the adverse effects and is a multifactorial systemic skeletal disease associated with bone fragility and an increased risk of fracture. We performed a longitudinal, comprehensive, nested case-control study to explore the effect of ART on the risk of osteoporosis in 104 osteoporotic and 416 non-osteoporotic patients with HIV infection at their average age about 29 years old in Taiwan. Patients with history of ART, current exposure to ART, higher cumulative defined daily doses (DDDs), or higher ART adherence were at a higher risk of osteoporosis (p < 0.05). Patients receiving nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-containing regimen (zidovudine-lamivudine combination, lamivudine-abacavir combination, and abacavir alone) and protease inhibitor (PI)-containing regimen (lopinavir-ritonavir combination, ritonavir, and atazanavir) had a higher risk of osteoporosis (p < 0.05). Especially, patients receiving high doses of the PIs lopinavir-ritonavir combination had an increased risk of osteoporosis (p < 0.05). In conclusion, history of ART, current exposure to ART, higher cumulative DDDs, and higher ART adherence were associated with an increased risk of osteoporosis. Furthermore, NRTI- and PI-containing regimens and high doses of PIs lopinavir-ritonavir combination may be associated with an increased risk of osteoporosis in patients with HIV infection in Taiwan.

Integrating transcriptome-wide association study and mRNA expression profile identified candidate genes related to hand osteoarthritis

BackgroundOsteoarthritis (OA) is a common skeletal system disease that has been partially attributed to genetic factors. The hand is frequently affected, which seriously affects the patient’s quality of life. However, the pathogenetic mechanism of hand osteoarthritis (hand OA) is still elusive.MethodsA genome-wide association study (GWAS) summary of hand OA was obtained from the UK Biobank dataset, which contains data from a total of 452,264 White British individuals, including 37,782 OA patients. The transcriptome-wide association study (TWAS) of hand OA was performed using FUnctional Summary-based ImputatiON (FUSION) with the skeletal muscle and blood as gene expression references. The significant genes identified by TWAS were further subjected to gene set enrichment analysis (GSEA) with the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. Furthermore, we compared the genes and gene sets identified by our TWAS with that of a knee OA mRNA expression profile to detect the genes and gene sets shared by TWAS and mRNA expression profiles in OA. The mRNA expression profiles of 18 normal knee cartilages and 20 OA knee cartilages were acquired from the Gene Expression Omnibus database (accession number: GSE114007).ResultsTWAS identified 177 genes with P < 0.05 for the skeletal muscle, including ANKRD44 (P = 0.0001), RIC3 (P = 0.0003), and AC005154.6 (P = 0.0004). TWAS identified 423 genes with P < 0.05 for the blood, including CRIM1 (P = 0.0002), ZNF880 (P = 0.0002), and NCKIPSD (P = 0.0003). After comparing the results of the TWAS to those of the mRNA expression profiling of OA, we identified 5 common genes, including DHRS3 (log2fold = − 1.85, P = 3.31 × 10− 9) and SKP2 (log2fold = 1.36, P = 1.62 × 10− 8). GSEA of TWAS identified 51 gene ontology (GO) terms for hand OA, for example, protein binding (P = 0.0003) and cytosol (P = 0.0020). We also detected 6 common GO terms shared by TWAS and mRNA expression profiling, including protein binding (PTWAS = 2.54 × 10− 4, PmRNA = 3.42 × 10− 8), extracellular exosome (PTWAS = 0.02, PmRNA = 1.18 × 10− 4), and cytoplasm (PTWAS = 0.0183, PmRNA = 0.0048).ConclusionIn this study, we identified 5 candidate genes and 6 GO terms related to hand OA, which may help to uncover the pathogenesis of hand OA. It should be noted that the possible difference in the gene expression profiles between hand OA and knee OA may affect our study results, which should be interpreted with caution.

The prevention of osteoporosis and sarcopenia in older adults.

Osteoporosis and sarcopenia are common in older adults. Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Bone fractures can result in changes in posture, pain, the need for surgical repair and functional impairment. Sarcopenia is the progressive and generalized loss of skeletal muscle mass, strength and/or physical performance. Older adults with sarcopenia experience increased risk of frailty, disability, hospitalizations, mortality, and a reduced quality of life. In this narrative review we provide guidance regarding the prevention of both osteoporosis and sarcopenia, including interventions that prevent both conditions from occurring, recommended screening and treatment to prevent progression.

LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells.

Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adverse effects. Cell replacement therapy using mesenchymal stem cells (MSCs) could serve as a treatment strategy for osteoporosis in the future. LIGHT (HVEM-L, TNFSF14, or CD258) is a member of the tumor necrosis factor superfamily. However, the effect of recombinant LIGHT (rhLIGHT) on osteogenesis in human bone marrow-derived MSCs (hBM-MSCs) is unknown. Therefore, we monitored the effects of LIGHT on osteogenesis of hBM-MSCs. Lymphotoxin-β receptor (LTβR), which is a LIGHT receptor, was constitutively expressed on the surface of hBM-MSCs. After rhLIGHT treatment, calcium and phosphate deposition in hBM-MSCs, stained by Alizarin red and von Kossa, respectively, significantly increased. We performed quantitative real-time polymerase chain reaction to examine the expressions of osteoprogenitor markers (RUNX2/CBFA1 and collagen I alpha 1) and osteoblast markers (alkaline phosphatase, osterix/Sp7, and osteocalcin) and immunoblotting to assess the underlying biological mechanisms following rhLIGHT treatment. We found that rhLIGHT treatment enhanced von Kossa- and Alizarin red-positive hBM-MSCs and induced the expression of diverse differentiation markers of osteogenesis in a dose-dependent manner. WNT/β-catenin pathway activation strongly mediated rhLIGHT-induced osteogenesis of hBM-MSCs, accelerating the differentiation of hBM-MSCs into osteocytes. In conclusion, the interaction between LIGHT and LTβR enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy.

Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma-Induced Osteolysis and Reduces Overall Survival.

Multiple myeloma promotes systemic skeletal bone disease that greatly contributes to patient morbidity. Resorption of type I collagen-rich bone matrix by activated osteoclasts results in the release of sequestered growth factors that can drive progression of the disease. Matrix metalloproteinase-13 (MMP13) is a collagenase expressed predominantly in the skeleton by mesenchymal stromal cells (MSC) and MSC-derived osteoblasts. Histochemical analysis of human multiple myeloma specimens also demonstrated that MMP13 largely localizes to the stromal compartment compared with CD138+ myeloma cells. In this study, we further identified that multiple myeloma induces MMP13 expression in bone stromal cells. Because of its ability to degrade type I collagen, we examined whether bone stromal-derived MMP13 contributed to myeloma progression. Multiple myeloma cells were inoculated into wild-type or MMP13-null mice. In independent in vivo studies, MMP13-null mice demonstrated significantly higher overall survival rates and lower levels of bone destruction compared with wild-type controls. Unexpectedly, no differences in type I collagen processing between the groups were observed. Ex vivo stromal coculture assays showed reduced formation and activity in MMP13-null osteoclasts. Analysis of soluble factors from wild-type and MMP13-null MSCs revealed decreased bioavailability of various osteoclastogenic factors including CXCL7. CXCL7 was identified as a novel MMP13 substrate and regulator of osteoclastogenesis. Underscoring the importance of host MMP13 catalytic activity in multiple myeloma progression, we demonstrate the in vivo efficacy of a novel and highly selective MMP13 inhibitor that provides a translational opportunity for the treatment of this incurable disease. SIGNIFICANCE: Genetic and pharmacologic approaches show that bone stromal-derived MMP13 catalytic activity is critical for osteoclastogenesis, bone destruction, and disease progression. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/9/2415/F1.large.jpg.

Анализ эффективности внедрения системы скрининга остеопороза

Osteoporosis is defined as a systemic skeletal disease characterized by low mineral bone mass and microarchitectural deterioration of bone tissue. This consequently increases bone fragility and susceptibility to fracture. Osteoporosis affects every third woman and every fourth man over 50 years old. Osteoporosis is a heavy burden for the health care of the Russian Federation, defined as RUB25 billion annually. Up to 31% of women and 4% of men over 50 years of age need special therapy for prevents the destruction of bone tissue. Identification of these risk groups allows early treatment and prevention of pathological fractures. The paper analyzes modern approaches to the diagnosis of osteoporosis. An overview of diagnostic methods is given, including artificial intelligence technologies for recognizing low-energy vertebral fractures, as well as methods of routine dual-energy absorptiometry DXA. CT bone densitometry technic (QCT) are also discussed. The principle of the FRAX tool is presented to identify patients at high risk of low-energy fractures, as well as to determine the groups of patients in need of densitometric studies. Various models of osteoporosis screening are analyzed, with an assessment of their medical and economic efficiency. The economic substantiation of the most effective strategy – conducting a questionnaire on FRAX followed by densitometric studies is presented. This will prevent more than 50% of low energy fractures without increasing costs. These efforts are aimed at increasing quality of life old population. This will contribute to the achievement of the targets set in the national project “Demography”.

Efficacy and safety of Xianling Gubao capsule in treating postmenopausal osteoporosis: A protocol for systematic review and meta-analysis.

Background:postmenopausal osteoporosis is a systemic metabolic skeletal disease associated with menopause-related estrogen withdrawal. postmenopausal osteoporosis is characterized by low bone mass, bone microstructure destruction, leading to increased bone brittleness and be prone to fracture, resulting in disability and death. At present, the commonly used drugs are estrogen, calcium, bone formation promoter and bone resorption inhibitor, and the side effects are obvious. In Traditional Chinese medicine, kidney-tonifying differentiating medicine is guided by the whole concept, Xianling Gubao capsule as the representative, the treatment of postmenopausal osteoporosis has certain therapeutic advantages, but lacks evidence-based medicine evidence. The purpose of this study is to systematically study the efficacy and safety of Xianling Gubao capsule in the treatment of postmenopausal osteoporosis.Methods:use computer to search English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China Knowledge Network, Wanfang, Weipu, Chinese Biomedical Database), in addition manually search Baidu academic, Google academic, from the establishment of database to October 2020, for randomized controlled clinical study of postmenopausal osteoporosis in the Xianling Gubao capsule treatment. Two researchers independently did the data extraction and literature quality evaluation, using RevMan5.3 software to do meta-analysis of the included literature.Results:this study assessed the efficacy and safety of xianling gubao capsule in the treatment of postmenopausal osteoporosis by total effective rate, bone density after treatment, blood calcium level after treatment, blood phosphorus level after treatment, pain score, quality of life and so on.Conclusion:this study will provide reliable evidence-based evidence for the clinical application of Xianling Gubao capsule in the treatment of postmenopausal osteoporosis.OSF Registration number:DOI 10.17605/OSF.IO/TP394

Artemisinin Reverses Glucocorticoid-Induced Injury in Bone Marrow-Derived Mesenchymal Stem Cells through Regulation of ERK1/2-CREB Signaling Pathway.

Glucocorticoids are the most common cause of secondary osteoporosis, which affects both women (pre- and postmenopausal) and men. In cases of prolonged treatment, glucocorticoids promote the loss and inactivation of the differentiational function of bone marrow mesenchymal stromal cells (BMSCs), risking the development of skeletal system diseases such as osteoporosis. This study reports for the first time the protective effect of the antimalarial artemisinin against glucocorticoid-induced insults on primary cultured rat BMSCs. At relatively low concentrations, artemisinin treatment improved BMSC survival by promoting a decline of reactive oxygen species (ROS) production that correlated with the decrease of caspase-3 activation, LDH release, mitochondrial membrane potential (Δψm) loss, and apoptosis induced by dexamethasone (DEXA). In addition, artemisinin improved the osteogenic differentiation of DEXA-damaged cells. DEXA inhibited extracellular-signal-regulated kinase 1/2 (ERK1/2) and cAMP response element binding protein (CREB) phosphorylation, and artemisinin treatment promoted their activation in a concentration-dependent manner. PD98059, the specific inhibitor of the ERK1/2 pathway, blocked ERK1/2 phosphorylation and artemisinin protection. Similarly, siCREB attenuated the protective effect of artemisinin, strongly suggesting the involvement of the ERK1/2-CREB pathway in the protective action of artemisinin against DEXA-induced damage in BMSCs. In addition, we found that the expression of antiapoptotic protein B-cell lymphoma 2 protein (BCL-2) was also upregulated by artemisinin. These studies demonstrate the therapeutic potential of artemisinin in the survival improvement of BMSCs exposed to glucocorticoid-induced apoptosis and suggest that artemisinin-mediated protection may occur via the activation of ERK1/2-CREB signaling pathway.

Fibronectin 1 activates WNT/β-catenin signaling to induce osteogenic differentiation via integrin β1 interaction

AbstractOsteoporosis (OP) is a systemic skeletal disease leading to fragility fractures and is a major health issue globally. WNT/β-catenin signaling regulates bone-remodeling processes and plays vital roles in OP development. However, the underlying regulatory mechanisms behind WNT/β-catenin signaling in OP requires clarification, as further studies are required to identify novel alternate therapeutic agents to improve OP. Here we report that fibronectin 1 (FN-1) promoted differentiation and mineralization of osteoblasts by activating WNT/β-catenin pathway, in cultured pre-osteoblasts. With isobaric tags for relative and absolute quantitation labeling proteomics analysis, we investigated protein changes in bone samples from OP patients and normal controls. FN-1 accumulated in osteoblasts in bone samples from OP patients and age-related OP mice compared to control group. In addition, we observed that integrin β1 (ITGB1) acts as an indispensable signaling molecule for the interplay between FN-1 and β-catenin, and that FN-1 expression increased, but ITGB1 expression decreased in osteoblasts during OP progression. Therefore, our study reveals a novel explanation for WNT/β-catenin pathway inactivation in OP pathology. Supplying of FN-1 and ITGB1 may provide a potential therapeutic strategy in improving bone formation during OP.Fibronectin 1 (FN-1) promotes differentiation and mineralization of osteoblasts by activating the WNT/β-catenin pathway. Integrin β1 (ITGB1) acts as an indispensable signaling molecule for the interplay between FN-1 and β-catenin. Treatment with FN-1 and ITGB1 is a potential therapeutic strategy for improvement of bone formation in osteoporosis.

Air Pollutants Interaction and Gender Difference on Bone Mineral Density T-Score in Taiwanese Adults.

Osteoporosis is defined as a systemic skeletal disease characterized by a reduction in bone mass and microarchitectural deterioration of bone tissue. Previous studies have reported associations between air pollution and lower bone mineral density; however, few studies have investigated the association between air pollution and osteoporosis. In this study, we combined two databases, the first including 5000 individuals registered in the Taiwan Biobank, and the second containing detailed daily data on air pollution. After multivariable adjustments, ozone (O3) (unstandardized coefficient β, 0.015; p = 0.008) was significantly positively associated with T-score, whereas carbon monoxide (CO) (unstandardized coefficient β, −0.809; p < 0.001), sulfur dioxide (SO2) (unstandardized coefficient β, −0.050; p = 0.005), nitric oxide (NO) (unstandardized coefficient β, −0.040; p < 0.001), nitrogen dioxide (NO2) (unstandardized coefficient β, −0.023; p < 0.001), and nitrogen oxide (NOx) (unstandardized coefficient β, −0.017; p < 0.001) were significantly negatively associated with T-score. The interactions between CO and NOx (p = 0.001) and SO2 and NO2 (p = 0.004) on T-score were statistically significant. An increase in exposure to CO, NO and NOx was associated with a faster decline in T-score in the female participants compared to the male participants. In addition, an increase in O3 was associated with a faster increase in T-score in the female participants compared to the male participants. In conclusion, the air pollutants CO, SO2, NO, NO2, and NOx were associated with osteoporosis. In addition, there were interaction and synergetic effects between CO and NOx and SO2 and NO2 on T-score. We also observed differences in the associations between air pollutants and T-score between the female and male participants.

Best Performance Parameters of HR-pQCT to Predict Fragility Fracture: Systematic Review and Meta-Analysis.

ABSTRACTOsteoporosis is a systemic skeletal disease characterized by low bone mass and bone structural deterioration that may result in fragility fractures. Use of bone imaging modalities to accurately predict fragility fractures is always an important issue, yet the current gold standard of dual‐energy X‐ray absorptiometry (DXA) for diagnosis of osteoporosis cannot fully satisfy this purpose. The latest high‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a three‐dimensional (3D) imaging device to measure not only volumetric bone density, but also the bone microarchitecture in a noninvasive manner that may provide a better fracture prediction power. This systematic review and meta‐analysis was designed to investigate which HR‐pQCT parameters at the distal radius and/or distal tibia could best predict fragility fractures. A systematic literature search was conducted in Embase, PubMed, and Web of Science with relevant keywords by two independent reviewers. Original clinical studies using HR‐pQCT to predict fragility fractures with available full text in English were included. Information was extracted from the included studies for further review. In total, 25 articles were included for the systematic review, and 16 articles for meta‐analysis. HR‐pQCT was shown to significantly predict incident fractures and/or major osteoporotic fractures (MOFs). Of all the HR‐pQCT parameters, our meta‐analysis revealed that cortical volumetric bone mineral density (Ct.vBMD), trabecular thickness (Tb.Th), and stiffness were better predictors. Meanwhile, HR‐pQCT parameters indicated better performance in predicting MOFs than incident fractures. Between the two standard measurement sites of HR‐pQCT, the non‐weight‐bearing distal radius was a more preferable site than distal tibia for fracture prediction. Furthermore, most of the included studies were white‐based, whereas very few studies were from Asia or South America. These regions should build up their densitometric databases and conduct related prediction studies. It is expected that HR‐pQCT can be used widely for the diagnosis of osteoporosis and prediction of future fragility fractures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Network pharmacology-based investigation on the mechanisms of action of Morinda officinalis How. in the treatment of osteoporosis

BackgroundOsteoporosis is a systemic skeletal disease that leads to a high risk for bone fractures. Morinda officinalis How. has been used as osteoporosis treatment in China. However, its mechanism of action as an anti-osteoporotic herb remains unknown. MethodsA network pharmacology approach was applied to explore the potential mechanisms of action of M. officinalis in osteoporosis treatment. The active compounds of M. officinalis and their potential osteoporosis-related targets were retrieved from TCMSP, TCMID, SwissTargetPrediction, DrugBank, DisGeNET, GeneCards, OMIM, and TTD databases. A protein–protein interaction network was built to analyze the target interactions. The Metascape database was used to carry out GO enrichment analysis and KEGG pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking. ResultsA total of 17 active compounds and 93 anti-osteoporosis targets of M. officinalis were selected for analysis. The GO enrichment analysis results indicated that the anti-osteoporosis targets of M. officinalis mainly play a role in the response to steroid hormone. The KEGG pathway enrichment analysis showed that M. officinalis prevents osteoporosis through the ovarian steroidogenesis signaling pathway. Moreover, the molecular docking results indicated that bioactive compounds (morindon, ohioensin A, and physcion) demonstrated a good binding ability with IGF1R, INSR, ESR1, and MMP9. ConclusionM. officinalis contains potential anti-osteoporotic active compounds. These compounds function by regulating the proteins implicated in ovarian steroidogenesis-related pathways that are crucial in estrogen biosynthesis. Our study provides new insights into the development of a natural therapy for the prevention and treatment of osteoporosis.

Osteoporosis and Health-Related Quality of Life Among Older Women

Background: Osteoporosis, a systemic skeletal disease characterized by low bone mass, poses a significant disease burden for older women. Often assessed using Health-Related Quality of Life (HRQoL) scale, the association between osteoporosis and HRQoL is scarce, with the majority of quality of life studies focused on osteoporotic women post fracture. Purpose: The study’s primary objectives were to examine if differences exist in HRQoL among women greater than 50 years of age who have and/or do not have osteoporosis and to gain insight into the relationship of HRQoL and osteoporosis.Methods: A retrospective cross-sectional design involving data extraction on women aged 50 years or older from 2014 Medical Expenditure Panel Survey (MEPS) was used (N = 4,661). HRQoL was measured by the generic Short-Form-12 Version 2 Physical (PCS) and Mental Health (MCS) component summary scores. The differences between osteoporosis and PCS and MCS were examined using t-tests and multivariable ordinary least squares regression.Results: Overall, 4.1% women aged 50 and older had osteoporosis. In both bivariate and multivariable analyses, no statistically significant differences were observed in HRQoL measures between women with and/or without osteoporosis. Conclusion: No group differences in HRQoL by osteoporosis status suggest the need for additional research using other research methodologies to flush out nuances in QOL changes. Clinician actions focused on insured and uninsured women with osteoporosis must include early and ongoing QOL assessment, with a focus on physical changes overtime

Cherubism: A systemic skeletal disease? About a case report

Cherubism: A systemic skeletal disease? About a case report

COPD and Osteoporosis: Associated Factors in Patients Treated with Inhaled Corticosteroids.

PurposeOsteoporosis is a systemic skeletal disease with a consequent increase in fractures rates. Osteoporosis may be primary which is related with normal aging, or secondary which occurs in the presence of an underlying disease or medication. Osteoporosis is one of the significant comorbidities in chronic obstructive pulmonary disease (COPD). In this study, we aimed to investigate the presence of osteoporosis and the influencing factors in COPD patients.Patients and MethodsThis is a two-group comparison study that was conducted among 30 COPD patients on inhaled corticosteroid (ICS) and 33 controls. It was conducted in the outpatient clinics at the Departments of Physical Medicine and Rehabilitation and Pulmonary Diseases in Bursa Uludag University Hospital, a tertiary reference center, in the northwest region of Turkey. For both groups, demographic variables, osteoporosis risk questioning, body mass index (BMI), bone mineral density (BMD), biochemical blood tests, vertebral fractures on lumbar and thoracic x-rays were recorded. COPD patients were also evaluated for lung functions via spirometry.ResultsThirty patients with COPD (Group 1) and 33 controls (Group 2) were included in the study. Comparing the demographic and biochemical data, no difference was found between the groups except smoking (pack/year) (p<0.001) and erythrocyte sedimentation rate (p<0.001), which were significantly high in COPD group. BMD in the COPD group was significantly lower in both hip and lumbar regions compared with the controls. There were significant correlations between L2 BMD values and pulmonary function tests. BMI was significantly low in osteoporotic COPD patients when compared with the non-osteoporotic COPD patients (p=0.002).ConclusionIn patients with COPD using inhaled corticosteroids, BMD was significantly low compared with the controls. Osteoporotic COPD patients had significantly lower BMI than non-osteoporotic. These findings suggest that pulmonary dysfunction and low BMI are associated with osteoporosis in COPD patients.

Pharmacological agents and natural compounds: available treatments for osteoporosis.

Osteoporosis, a systemic skeletal disease characterized by a decrease in bone mass and deterioration of bone structure leading to an increased risk of fragility fractures, represents one of the major health problems worldwide. Currently, there are numerous pharmacological products used for the treatment of osteoporosis. Anti-resorptive drugs include bisphosphonates, hormone therapy, selective estrogen-receptor modulators, calcitonin, denosumab, calcium and vitamin D supplementation. Anabolic drugs such as teriparatide, strontium ranelate, romosozumab have recently become available based on advanced clinical trials. In recent years, combination therapy of anabolic and anti-resorptive agents is expected to be ideal anti-osteoporosis option. The adverse side effects caused by the long-term administration of pharmacological drugs have prompted researchers to study natural therapeutic compounds to find an alternative and effective way for osteoporosis treatment. Natural compounds including phytoestrogens with estrogenic effects (e.g. genistein, daidzein, icariin, dioscin, Ginkgo biloba), antioxidant and anti-inflammatory agents (e.g. acteoside, curcumin, resveratrol, Camellia sinensis), treatments that exert their effects by multiple actions (e.g. kinsenoside, berberine, Olea europaea, Prunus domestica, Allium cepa) could provide a safer alternative to primary pharmacological strategies. In this review, both pharmacological agents and natural compounds as available treatments for osteoporosis are characterized. In addition, possible mechanisms of action of all aforementioned treatments associated with bone remodelling, osteoclastogenesis, osteoblastogenesis, bone cell activity, death, and oxidative stress are presented. Nevertheless, more high-quality clinical studies with natural compounds are needed to provide greater evidence of the beneficial and safer antiosteoporotic application for the candidate.

MORPHOMETRIC BONE EVALUATION OF MEN AND WOMEN OF DIFFERENT AGES BY CONE BEAM COMPUTED TOMOGRAPHY

Osteoporosis is a worldwide public health problem, defined as a systemic skeletal disease with decreased bone mass, and consequently bone fragility and risk of fractures. Our objective was to evaluate bone morphometry and correlate the morphometric indices between the men and women groups and women of different age groups. The sample was divided into groups: (A) men aged 65 to 75 years, (B1) women aged 45 to 55 years, (B2) women aged 55 to 65 years, and (B3) women aged 65 to 75 years. Morphometric indices were analyzed in the region of the mental foramen in a coronal section and panoramic reconstructions of cone beam computed tomography (CBCT) through OnDemand3-D software. Computed Tomography Canine Index (CTCI), Computed Tomography Mentual Index (CTMI), Superior Computed Tomography Index (SCTI), and Inferior Computed Tomography Index (ICTI) were used. There were significant differences between the different groups in the IMTC, ITC(i), and ITC(s) and high correlation between indices. There was no difference in the qualitative index ICTC when used in isolation. There are differences in the bone structure of men and women and among women of different age groups, and the quantitative and qualitative indices may be a useful tool in the detection of patients with low bone mineral density when used together for subsequent referral to bone densitometry and specialized medical treatment.