OBJECTIVES: This study aimed to explore the active components, potential targets, and mechanism of Cnidii Fructus in the treatment of periodontitis with osteoprosis through network pharmacology, molecular docking, and molecular dynamics simulation technology. METHODS: The main chemical constituents and targets of Cnidii Fructus were screened using the TCMSP and SwissTargetPrediction databases, as well as literature reports. Targets of periodontitis and osteoporosis were predicted using different databases. The intersection targets of Cnidii Fructus, periodontitis, and osteoporosis were obtained using Venny 2.1. The protein-protein interaction network was formed on the STRING platform. Cytoscape 3.9.1 was used to construct the active component-intersection target interaction network, perform the topological analysis, and screen key targets and core active components. Furthermore, the Metascape database was used to perform gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis on the intersection targets. The top five key targets and core active components were selected as receptor proteins and ligand small molecules. Discovery Studio 2019 was used to dock ligands and receptors and visualize the docking results. Molecular dynamics simulation was conducted using Gromacs2022.3 to assess the stability of the interactions between the core active components and the main targets. RESULTS: A total of 20 potential active ingredients of Cnidii Fructus were screened, and 116 targets of Cnidii Fructus were obtained for treating periodontitis and osteoporosis. GO and KEGG analyses of the 116 targets showed that Cnidii Fructus may play a therapeutic role through the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) and advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathways. Molecular docking showed that the core constituents were well bound to the main targets. Molecular dynamics simulations confirmed the stability of the Diosmetin-AKT1 complex system. CONCLUSIONS The preliminary discovery of the potential molecular pharmacological mechanism of Cnidii Fructus extract in the targeted treatment of periodontitis with osteoporosis through a multi-component, multitarget, and multi-pathway approach can serve as a theoretical foundation for future drug-development research and clinical application.
Molecular Docking Simulation ; Molecular Dynamics Simulation ; Network Pharmacology ; Periodontitis/complications* ; Drugs, Chinese Herbal/chemistry* ; Osteoporosis/complications* ; Humans ; Protein Interaction Maps ; Cnidium/chemistry*

Quantitative CT (QCT) is a method of measuring bone mineral density (BMD) of human based on a CT machine,calibrated by QCT body model and analyzed by professional software.Compared with dual-energy X-ray absorptiometry,QCT can not only assess the cortical and cancellous BMD but also exclude the influences of osteophytes and aortic/vascular calcification,thus being capable of accurately reflecting patients' bone mass.In recent years,increasing studies on QCT and osteoporosis (OP) have been carried out,and the application of QCT in the diagnosis of OP,evaluation of vertebral bone conditions,prediction of fracture risks,and assessment of anti-OP treatment is garnering increasing attention from researchers at home and abroad.This article reviews the research progress in this field,aiming to provide a reference for the research on QCT in the diagnosis and treatment of OP.
Humans ; Osteoporosis/diagnosis* ; Tomography, X-Ray Computed/methods* ; Bone Density

BACKGROUND

This first clinical practice guideline (CPG) on osteoporosis prevention and management in the Philippines is the output of a shared undertaking by a multidisciplinary CPG development team spearheaded by the Osteoporosis Society of the Philippines Foundation, Inc. and joined by the Philippine Academy of Family Physicians; the Philippine College of Endocrinology, Diabetes, and Metabolism; the Philippine Orthopedic Association; the Philippine Obstetrics and Gynecological Society and the Philippine Rheumatology Association. This guideline seeks to augment and update the "Consensus statements on osteoporosis diagnosis, prevention and management in the Philippines," initially published in 2011, incorporating evidence-based practices developed in the last decade.

The steering committee formulated and prioritized clinical questions based on meetings and stakeholder consultations. A PICO (population, intervention, comparator, outcome) format was used to develop clinical questions and guide the systematic search for evidence. The development of guidelines followed the ADAPTE process. Once completed, panel discussions were done using the Evidence to Decision Framework. After the panel discussions, the final recommendations were revised.

Thirty-four recommendations were formulated to address 27 clinical questions related to screening, prevention, diagnosis, pharmacologic and nonpharmacologic treatment, surgical management, follow-up, and continuity of care. With these recommendations, the developers aim to establish a standard of care in the prevention, diagnosis and management of osteoporosis and fragility fractures in both in-patient and out-patient cases that are appropriate to the Philippine context. Specifically, the CPG development group aims to use these recommendations to define the standard of care for osteoporosis as part of universal healthcare services once the program is implemented nationally. Relevant stakeholders may also use the recommendations to inform public and private payor policies for patients with fragility fractures, as well as by local government units or private companies looking to establish orthogeriatric centers with fracture liaison services.

This guideline is helpful for physicians and other allied health personnel in screening, diagnosis, management and prevention of primary osteoporosis and fragility fractures among postmenopausal women and older men.

BACKGROUND: High visceral fat mass (FM) is associated with a high risk of cardiometabolic morbidity. Meanwhile, loss of skeletal muscle (lean mass, LM) has been suggested to contribute to metabolic diseases. METHODS: We investigated associations between cardiometabolic diseases and dual energy X-ray absorptiometry (DXA)-measured body composition indices, including the FM index (FM/height²), percent body fat, trunk-to-appendicular fat ratio (TAR), trunk-to-leg fat ratio (TLR), LM index (LM/height²) and FM-to-LM ratio in 595 community-dwelling elderly Japanese men (mean age, 74 years; standard deviation, 6; range, 65 to 94). Hypertension was identified as high blood pressure and/or the use of antihypertensive drugs. Diabetes was identified as high hemoglobin A1c and/or the use of antidiabetic drugs. The ability of DXA-based indices to discriminate between the presence and absence of cardiometabolic diseases was evaluated using area under the curve (AUC) calculated by receiver operating characteristic curve analysis. RESULTS: Body mass index, FM index, percent body fat, TAR, TLR and FM-to-LM ratio were significantly associated with hypertension (P < 0.05). TAR and TLR, but not body mass index, FM index, percent body fat, LM index and FM-to-LM ratio, showed significant positive associations with diabetes. The AUC for the LM index was significantly lower than those for the FM index, percent body fat and FM-to-LM ratio. No associations were observed between the LM index and hypertension, dyslipidemia and diabetes. CONCLUSION The association between cardiometabolic function and LM, which includes skeletal muscle, may not be as pronounced or stronger than associations between cardiometabolic function and FM. Further detailed studies are needed to clarify how skeletal muscle contributes to cardiometabolic disease.
Humans ; Male ; Absorptiometry, Photon ; Aged ; Japan/epidemiology* ; Body Composition ; Aged, 80 and over ; Hypertension/epidemiology* ; Cardiovascular Diseases/epidemiology* ; Body Mass Index ; Muscle, Skeletal ; Osteoporosis/epidemiology* ; Diabetes Mellitus/epidemiology* ; Risk Factors ; East Asian People

OBJECTIVE: To investigate the effect of human adipose-derived mesenchymal stem cells (hASCs) exosomes on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) extracted from osteoporotic mice, and to evaluate the effect of hASCs exosomes on preventing bone loss induced by estrogen deficiency. METHODS: hASCs exosomes were extracted by ultracentrifugation. The osteoporotic mice were established by bilateral ovariectomy (OVX). BMSCs were isolated from osteo-porotic mice and cultured for further analysis. In the experimental group, these BMSCs were exposed to an osteogenic induction medium supplemented with hASCs exosomes to evaluate their potential effects on osteogenesis. In contrast, the control group was treated with the same osteogenic induction medium, but without the addition of hASCs exosomes, to serve as a baseline comparison for the study. To comprehensively assess the osteogenic differentiation of BMSCs influenced by hASCs exosomes, alkaline phosphatase (ALP) staining, ALP activity quantitative analysis and quantitative reverse transcription polymerase chain reaction (qPCR) were performed. These evaluations provided critical insights into the role of hASCs exosomes in promoting osteoblast differentiation and bone formation in osteoporotic conditions. The fluorescence labeled hASCs exosomes were injected via the tail vein to observe the biodistribution of exosomes. Two weeks after OVX, the mice were divided into three groups: The experimental group consisted of estrogen-deficient mice receiving hASCs exosome injections; the negative control group consisted of estrogen-deficient mice receiving phosphate-buffered saline (PBS) injections; and the positive control group consisted of mice that underwent Sham surgery and received PBS injections.The injections were administered once every 3 days, for a total of 8 injections. Afterward, the femurs were collected from the mice, and micro-computed tomography (micro-CT) was performed to measure bone mineral density and conduct bone morphometric analysis. RESULTS: hASCs exosomes were successfully extracted using ultracentrifugation. After the induction by hASCs exosomes, ALP staining and ALP activity in the BMSCs extracted from osteoporotic mice were significantly enhanced, the expression of osteogenesis related genes in BMSCs were significantly up-regulated. More trabecular bone and higher bone mineral density were observed in estrogen-deficient mice injected with hASCs exosomes compared with estrogen-deficient mice injected with PBS, and there was no significant decrease in bone mineral density compared with the Sham operation group. CONCLUSION hASCs exosomes promoted the osteogenic differentiation of BMSCs extracted from osteoporotic mice. hASCs exosomes prevented bone loss induced by estrogen deficiency.
Animals ; Mesenchymal Stem Cells/cytology* ; Exosomes ; Estrogens/deficiency* ; Humans ; Osteogenesis ; Cell Differentiation ; Female ; Mice ; Osteoporosis/prevention & control* ; Ovariectomy ; Adipose Tissue/cytology* ; Cells, Cultured

Osteonecrosis of the mandible is also called avascular necrosis of the jaw, and it is a rare complication of bisphosphonates. It is characterized with pain, swelling, exposure of bone, local infection and pathologic fractures of the jaw. With the widespread usage of bisphosphonates in bone metastasis of malignant tumors and osteoporosis, this rare complication has received more attention in recent years. Here, we reported a case of bisphosphonates-related osteonecrosis of the jaw (BRONJ) caused by intravenous zoledronic acid for osteoporosis. A 62-year-old female patient with 7-year history of Sjögren's syndrome and 3-year history of osteoporosis developed BRONJ after 3-year treatment of zoledronic acid. Two months before she went to the Peking University International Hospital, she visited the dentist for periodontal purulent secretion and extracted one tooth from the right mandible. However, the condition was not improved and she felt persistent pain and swelling in the right mandible. Hence, she received repeated root curettage, but there was no improvement. Finally, she was diagnosed with osteonecrosis of the mandible based on the digital volume tomography scan, which showed right mandibular osteonecrosis bone destruction. She underwent surgical debridement of the necrotic bone and administered intravenous antibio-tics at the Peking University International Hospital. Histopathological analysis of the bone biopsy further confirmed the diagnosis of BRONJ. Her condition was improved successfully during a 3-year follow-up. Osteonecrosis of the mandible become more common with the increased use of bisphosphonates. Recent study has reported that osteonecrosis of the mandible is more likely to occur in patients with Sjögren's syndrome. In addition, age, long-term and irregular administration of glucocorticoids, irregular oral examination and treatment also might be the risk factors in the pathogenesis of osteonecrosis of the mandible. For the elder osteoporosis patients who would receive or had received bisphosphonate-related drugs, oral health status and the disease states associated with necrosis of the mandible such as Sjögren's syndrome should be comprehensively measured and fully evaluated during the whole process. Furthermore, to better understand and prevent or reduce the occurrence of this complication, we reviewed the patho-genesis, diagnosis, treatment, and prevention of BRONJ.
Humans ; Female ; Middle Aged ; Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology* ; Diphosphonates/administration & dosage* ; Zoledronic Acid ; Imidazoles/administration & dosage* ; Bone Density Conservation Agents/adverse effects* ; Osteoporosis/drug therapy*

OBJECTIVE: To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVES: The core pathology of osteoporosis lies in bone resorption exceeding bone formation; thus, promoting osteogenesis is a key therapeutic strategy. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) forms the biological basis of bone formation. Astragaloside IV (A-IV), a major active component of Astragalus membranaceus, is known to enhance osteogenesis, but its precise molecular mechanisms remain unclear. This study aims to investigate the effects of A-IV on the proliferation and osteogenic differentiation of BMSCs from osteoporotic rats and to elucidate its molecular mechanism through the regulation of microRNA-21 (miR-21) and Notch2 expression. METHODS: After 1 week of adaptive feeding, mature female SD rats were randomly divided into a sham-operated (Sham) group (n=4) and an ovariectomized (OVX) group (n=8) to establish an osteoporosis model. Twelve weeks after surgery, BMSCs were isolated from femoral bone marrow and cultured. Cells were divided into a S-BMSCs group (from Sham), an O-BMSCs group (from OVX), and an A-BMSCs group (from OVX-derived BMSCs treated with A-IV). S-BMSCs and O-BMSCs were induced for osteogenic differentiation using osteogenic induction medium, whereas A-BMSCs were treated with A-IV before induction. Flow cytometry was used to identify mesenchymal stem cell surface markers (CD29) and hematopoietic stem cell marker (CD34) to confirm BMSC characteristics. Cell proliferation was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Alizarin red staining was performed to quantify calcium nodule formation, and alkaline phosphatase (ALP) activity assays were used to evaluate osteogenic differentiation. Real-time reverse transcription PCR (real-time RT-PCR) was used to detect changes in osteogenic-related genes, runt-related transcription factor 2 (Runx2) and osteopontin (OPN), as well as miR-21 expression. Western blotting was performed to assess Runx2, OPN, and Notch2 protein expression. RESULTS: Flow cytometry confirmed that O-BMSCs retained the phenotypic characteristics of mesenchymal stem cells. A-IV significantly enhanced the proliferation of BMSCs from osteoporotic rats (P<0.05), increased ALP activity, and upregulated the mRNA and protein expression of Runx2 and OPN (P<0.05). Bioinformatic and experimental analyses demonstrated that miR-21 directly targeted Notch2. A-IV treatment increased miR-21 expression while suppressing Notch2 protein expression and inhibiting activation of the Notch signaling pathway (P<0.05). CONCLUSIONS Astragaloside IV promotes the osteogenic differentiation of BMSCs derived from osteoporotic rats by upregulating miR-21 expression and inhibiting the key Notch signaling protein Notch2, thereby relieving the Notch2-mediated suppression of osteogenesis.
Animals ; Triterpenes/pharmacology* ; Saponins/pharmacology* ; Osteogenesis/drug effects* ; MicroRNAs/metabolism* ; Rats, Sprague-Dawley ; Female ; Cell Differentiation/drug effects* ; Mesenchymal Stem Cells/drug effects* ; Signal Transduction/drug effects* ; Osteoporosis/pathology* ; Rats ; Cells, Cultured ; Receptor, Notch2/metabolism* ; Receptors, Notch/metabolism* ; Ovariectomy ; Cell Proliferation/drug effects*

Loss-of-function variants of low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation, culminating in diminished bone mass. Our previous study reported transcription factor osterix (SP7)‍-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration. However, the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown. In this study, we used mice with a conditional knockout (cKO) of LRP5 in mature osteoblasts, which presented decreased osteogenesis. The in vitro experimental results showed that SP7 could promote LRP5 expression, thereby upregulating the osteogenic markers such as alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and β‍-catenin (P<0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model of LRP5 cKO mice, resulting in increased bone mineral density (BMD) (P<0.001) and volumetric density (bone volume (BV)/total volume (TV)) (P<0.001), and decreased trabecular separation (Tb.‍Sp) (P<0.05). These data suggested that SP7 could ameliorate bone defect healing in LRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
Animals ; Low Density Lipoprotein Receptor-Related Protein-5/metabolism* ; Osteoporosis/genetics* ; Mice ; Mice, Knockout ; Sp7 Transcription Factor/physiology* ; Osteogenesis ; Bone Density ; Osteoblasts/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Mice, Inbred C57BL ; beta Catenin/metabolism*

OBJECTIVES: To analyze bone mass distribution and the factors affecting bone mass in a general Chinese Han cohort undergoing physical examinations at our center. METHODS: We retrospectively collected the data of bone mineral density (BMD) measurements from 30 599 healthy Han Chinese adults (age≥20 years) who underwent dual-energy X-ray absorptiometry scans at our hospital from July, 2013 to July, 2023. Basic parameters including height, body weight, and gender were recorded, and descriptive statistics and correlation analyses were performed using R software. RESULTS: In this cohort, the male individuals had a mean peak BMD of 1.00±0.12 g/cm² in the lumbar vertebrae, 0.94±0.14 g/cm² in the femoral neck, and 0.99±0.13 g/cm² in the total hip, significantly higher than the values in the female individuals [0.99±0.12 g/cm² in the lumbar vertebrae (P=0.022), 0.79±0.11 g/cm² in the femoral neck (P<0.001), and 0.88±0.11 g/cm² in the total hip (P<0.001)]. In the overall cohort, the BMD values of the lumbar spine and femur decreased with age after reaching their peak levels. There was a positive correlation between BMD value and body mass index (BMI) in both male and female individuals. The 2013-2014 period recorded the lowest BMD values in the lumbar, hip, and femoral neck, which tended to increase steadily in the following years (2015-2023). CONCLUSIONS Our data suggest that the BMD values vary among different populations, and future multi-center studies using more accurate BMD detection technology are warranted to capture the variation patterns of BMD with demographic characteristics of specific populations.
Humans ; Bone Density ; Absorptiometry, Photon ; Male ; Female ; Retrospective Studies ; Osteoporosis/diagnostic imaging* ; Adult ; Middle Aged ; Lumbar Vertebrae/diagnostic imaging* ; China/epidemiology* ; Femur Neck/diagnostic imaging* ; Aged ; Beijing/epidemiology* ; Young Adult