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International Journal of Molecular... May 2024Epidemiological evidence suggests existing comorbidity between postmenopausal osteoporosis (OP) and cardiovascular disease (CVD), but identification of possible shared...
Epidemiological evidence suggests existing comorbidity between postmenopausal osteoporosis (OP) and cardiovascular disease (CVD), but identification of possible shared genes is lacking. The skeletal global transcriptomes were analyzed in trans-iliac bone biopsies (n = 84) from clinically well-characterized postmenopausal women (50 to 86 years) without clinical CVD using microchips and RNA sequencing. One thousand transcripts highly correlated with areal bone mineral density (aBMD) were further analyzed using bioinformatics, and common genes overlapping with CVD and associated biological mechanisms, pathways and functions were identified. Fifty genes (45 mRNAs, 5 miRNAs) were discovered with established roles in oxidative stress, inflammatory response, endothelial function, fibrosis, dyslipidemia and osteoblastogenesis/calcification. These pleiotropic genes with possible CVD comorbidity functions were also present in transcriptomes of microvascular endothelial cells and cardiomyocytes and were differentially expressed between healthy and osteoporotic women with fragility fractures. The results were supported by a genetic pleiotropy-informed conditional False Discovery Rate approach identifying any overlap in single nucleotide polymorphisms (SNPs) within several genes encoding aBMD- and CVD-associated transcripts. The study provides transcriptional and genomic evidence for genes of importance for both BMD regulation and CVD risk in a large collection of postmenopausal bone biopsies. Most of the transcripts identified in the CVD risk categories have no previously recognized roles in OP pathogenesis and provide novel avenues for exploring the mechanistic basis for the biological association between CVD and OP.
Topics: Humans; Female; Osteoporosis, Postmenopausal; Aged; Middle Aged; Cardiovascular Diseases; Aged, 80 and over; Polymorphism, Single Nucleotide; Bone Density; Transcriptome; Gene Expression Profiling; RNA, Messenger; MicroRNAs
PubMed: 38791593
DOI: 10.3390/ijms25105554 -
International Journal of Molecular... May 2024A low-energy hit, such as a slight fall from a bed, results in a bone fracture, especially in the hip, which is a life-threatening risk for the older adult and a heavy...
Persistent Mesodermal Differentiation Capability of Bone Marrow MSCs Isolated from Aging Patients with Low-Energy Traumatic Hip Fracture and Osteoporosis: A Clinical Evidence.
A low-energy hit, such as a slight fall from a bed, results in a bone fracture, especially in the hip, which is a life-threatening risk for the older adult and a heavy burden for the social economy. Patients with low-energy traumatic bone fractures usually suffer a higher level of bony catabolism accompanied by osteoporosis. Bone marrow-derived stem cells (BMSCs) are critical in osteogenesis, leading to metabolic homeostasis in the healthy bony microenvironment. However, whether the BMSCs derived from the patients who suffered osteoporosis and low-energy traumatic hip fractures preserve a sustained mesodermal differentiation capability, especially in osteogenesis, is yet to be explored in a clinical setting. Therefore, we aimed to collect BMSCs from clinical hip fracture patients with osteoporosis, followed by osteogenic differentiation comparison with BMSCs from healthy young donors. The CD markers identification, cytokines examination, and adipogenic differentiation were also evaluated. The data reveal that BMSCs collected from elderly osteoporotic patients secreted approximately 122.8 pg/mL interleukin 6 (IL-6) and 180.6 pg/mL vascular endothelial growth factor (VEGF), but no PDGF-BB, IL-1b, TGF-b1, IGF-1, or TNF-α secretion. The CD markers and osteogenic and adipogenic differentiation capability in BMSCs from these elderly osteoporotic patients and healthy young donors are equivalent and compliant with the standards defined by the International Society of Cell Therapy (ISCT). Collectively, our data suggest that the elderly osteoporotic patients-derived BMSCs hold equivalent differentiation and proliferation capability and intact surface markers identical to BMSCs collected from healthy youth and are available for clinical cell therapy.
Topics: Humans; Mesenchymal Stem Cells; Osteoporosis; Cell Differentiation; Osteogenesis; Female; Aged; Hip Fractures; Male; Aging; Cells, Cultured; Adult; Cytokines; Middle Aged; Adipogenesis; Aged, 80 and over; Bone Marrow Cells
PubMed: 38791313
DOI: 10.3390/ijms25105273 -
Frontiers in Public Health 2024Physical frailty is an important issue in aging societies. Three models of physical frailty assessment, the 5-Item fatigue, resistance, ambulation, illness and loss of...
BACKGROUND
Physical frailty is an important issue in aging societies. Three models of physical frailty assessment, the 5-Item fatigue, resistance, ambulation, illness and loss of weight (FRAIL); Cardiovascular Health Study (CHS); and Study of Osteoporotic Fractures (SOF) indices, have been regularly used in clinical and research studies. However, no previous studies have investigated the predictive ability of machine learning (ML) for physical frailty assessment. The aim was to use two ML algorithms, random forest (RF) and extreme gradient boosting (XGBoost), to predict these three physical frailty assessment models.
MATERIALS AND METHODS
Questionnaires regarding demographic characteristics, lifestyle habits, living environment, and physical frailty assessment were answered by 445 participants aged 60 years and above. The RF and XGBoost algorithms were used to assess their scores for the three physical frailty indices. Furthermore, feature importance and Shapley additive explanations (SHAP) were used to determine the important physical frailty factors.
RESULTS
The XGBoost algorithm obtained higher accuracy for predicting the three physical frailty indices; the areas under the curve obtained by the XGBoost algorithm for the 5-Item FRAIL, CHS, and SOF indices were 0.84. 0.79, and 0.69, respectively. The feature importance and SHAP of the XGBoost algorithm revealed that systolic blood pressure, diastolic blood pressure, age, and body mass index play important roles in all three physical frailty models.
CONCLUSION
The XGBoost algorithm has a more accurate predictive rate than RF across all three physical frailty assessments. Thus, ML can be a useful tool for the early detection of physical frailty.
Topics: Humans; Machine Learning; Female; Aged; Male; Middle Aged; Frailty; Surveys and Questionnaires; Osteoporotic Fractures; Geriatric Assessment; Aged, 80 and over; Frail Elderly; Algorithms
PubMed: 38784574
DOI: 10.3389/fpubh.2024.1303958 -
Journal of Orthopaedic Surgery and... May 2024Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic...
BACKGROUND
Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing.
METHODS
MSCs were pretreated with or without different concentrations of Tanshinone IIA followed by HO treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel.
RESULTS
Tanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited HO-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed HO-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation.
CONCLUSIONS
Taken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from HO-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.
Topics: Animals; Abietanes; Female; Mesenchymal Stem Cells; Apoptosis; Mice, Inbred C57BL; Fracture Healing; Ovariectomy; Mice; Antioxidants; Hydrogen Peroxide; Osteogenesis; Osteoporotic Fractures
PubMed: 38783358
DOI: 10.1186/s13018-024-04793-x -
Bone Reports Jun 2024As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address...
As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD. 6-week old male C57BL/6 mice were randomly divided into control (CON) and disease model (STZ-Ad) groups, using a previously established streptozotocin- and adenine-diet-induced model. After 16 weeks of disease induction, both CON and STZ-Ad groups were subdivided into two treatment groups and given weekly subcutaneous injections of 100 μL vehicle (phosphorus buffered saline, PBS) or 10 mg/kg Romo. Mice were euthanized after 4 weeks of treatment via cardiac exsanguination and cervical dislocation. Hindlimb bones and L4 vertebrae were cleaned of soft tissue, wrapped in PBS-soaked gauze and stored at -20C. Right tibiae, femora, and L4s were scanned via microcomputed tomography; tibiae were then tested to failure in 4-pt bending while L4s were compression tested. Romo treatment significantly increased cortical and trabecular bone mass in both STZ-Ad and CON animals. These morphological improvements created corresponding increases in cortical bending strength and trabecular compression strength, with STZ-Ad treated mice surpassing vehicle CON mice in all trabecular mechanics measures. These results suggest that Romo retains its efficacy at increasing bone mass and strength in diabetic kidney disease.
PubMed: 38778834
DOI: 10.1016/j.bonr.2024.101774 -
Bone Reports Jun 2024Despite the dominant role of bone mass in osteoporotic fractures, aging bone tissue properties must be thoroughly understood to improve osteoporosis management. In this...
Despite the dominant role of bone mass in osteoporotic fractures, aging bone tissue properties must be thoroughly understood to improve osteoporosis management. In this context, collagen content and integrity are considered important factors, although limited research has been conducted on the tensile behavior of demineralized compact bone in relation to its porosity and elastic properties in the native mineralized state. Therefore, this study aims (i) at examining the age-dependency of mineralized bone and collagen micromechanical properties; (ii) to test whether, and if so to which extent, collagen properties contribute to mineralized bone mechanical properties. Two cylindrical cortical bone samples from fresh frozen human anatomic donor material were extracted from 80 proximal diaphyseal sections from a cohort of 24 female and 19 male donors (57 to 96 years at death). One sample per section was tested in uniaxial tension under hydrated conditions. First, the native sample was tested elastically (0.25 % strain), and after demineralization, up to failure. Morphology and composition of the second specimen was assessed using micro-computed tomography, Raman spectroscopy, and gravimetric methods. Simple and multiple linear regression were employed to relate morphological, compositional, and mechanical variables with age and sex. Macro-tensile properties revealed that only elastic modulus of native samples was age dependent whereas apparent elastic modulus was sex dependent ( < 0.01). Compositional and morphological analysis detected a weak but significant age and sex dependency of relative mineral weight ( = -0.24, < 0.05) and collagen disorder ratio (I/I, = 0.25, p < 0.05) and a strong sex dependency of bone volume fraction while generally showing consistent results in mineral content assessment. Young's modulus of demineralized bone was significantly related to tissue mineral density and Young's modulus of native bone. The results indicate that mechanical properties of the organic phase, that include collagen and non-collagenous proteins, are independent of donor age. The observed reduction in relative mineral weight and corresponding overall stiffer response of the collagen network may be caused by a reduced number of mineral-collagen connections and a lack of extrafibrillar and intrafibrillar mineralization that induces a loss of waviness and a collagen fiber pre-stretch.
PubMed: 38778833
DOI: 10.1016/j.bonr.2024.101773 -
PloS One 2024New vertebral compression fractures (NVCF) are common in patients with osteoporotic vertebral compression fractures (OVCF) who have undergone percutaneous vertebroplasty...
Prediction of new vertebral compression fracture within 3 years after percutaneous vertebroplasty for osteoporotic vertebral compression fracture: Establishment and validation of a nomogram prediction model.
New vertebral compression fractures (NVCF) are common in patients with osteoporotic vertebral compression fractures (OVCF) who have undergone percutaneous vertebroplasty (PVP). We sought to develop a nomogram prediction model for better identification and prevention of NVCF within 3 years after PVP in patients with OVCF. The demographic, clinical, and imaging data of patients who underwent PVP for OVCF between January 2010 and December 2019 were reviewed. Multivariate logistic regression analysis was used to screen for risk factors for NVCF within 3 years after PVP. A nomogram prediction model was then developed and validated to visually predict NVCF. The samples in the model were randomly divided into training and validation sets at a ratio of 7:3. Twenty-seven percent of patients experienced NVCF in other segments within 3 years after PVP. Older age, lower bone mineral density (BMD), smoking, lack of anti-osteoporosis therapy, and postoperative trauma were risk factors for NVCF. The area under the receiver operating characteristic curve suggested good discrimination of this model: training set (0.781, 95% confidence interval: 0.731-0.831) and validation set (0.786, 95% confidence interval: 0.708-0.863). The calibration curve suggested good prediction accuracy between the actual and predicted probabilities in the training and validation sets. The DCA results suggested that, when the probability thresholds were 0.0452-08394 and 0.0336-0.7262 in the training and validation set, respectively, patients can benefit from using this model to predict NVCF within 3 years after PVP. In conclusion, this nomogram prediction model that included five risk factors (older age, lower BMD, smoking, postoperative minor trauma, and lack of anti-osteoporosis treatment can effectively predict NVCF within 3 years after PVP. Postoperative smoking cessation, standard anti-osteoporosis treatment, and reduction in incidental minor trauma are necessary and effective means of reducing the incidence of NVCF.
Topics: Humans; Nomograms; Fractures, Compression; Spinal Fractures; Female; Male; Vertebroplasty; Osteoporotic Fractures; Aged; Risk Factors; Middle Aged; Aged, 80 and over; Bone Density; Retrospective Studies
PubMed: 38771842
DOI: 10.1371/journal.pone.0303385 -
Bioactive Materials Aug 2024Delayed bone-healing of senile osteoporotic fractures remains a clinical challenge due to the alterations caused by aging in bone and immune systems. The novel...
Delayed bone-healing of senile osteoporotic fractures remains a clinical challenge due to the alterations caused by aging in bone and immune systems. The novel biomaterials that address the deficiencies in both skeletal cells and immune systems are required to effectively treat the bone injuries of older patients. Zinc (Zn) has shown promise as a biodegradable material for use in orthopedic implants. To address the bone-healing deficiencies in elderly patients with bone injuries, we developed a biodegradable Zn-based alloy (Zn-2Cu-0.5Zr) with enhanced mechanical properties, including a yield strength of 198.7 MPa and ultimate tensile strength of 217.6 MPa, surpassing those of pure Zn and Zn-2Cu alloys. Cytotoxicity tests conducted on bone marrow mesenchymal stem cells (BMSCs) and MC3T3-E1 cells demonstrated that the extracts from Zn-2Cu-0.5Zr alloy exhibited no observable cytotoxic effects. Furthermore, the extracts of Zn-2Cu-0.5Zr alloy exhibited significant anti-inflammatory effects through regulation of inflammation-related cytokine production and modulation of macrophage polarization. The improved immune-osteo microenvironment subsequently contributed to osteogenic differentiation of BMSCs. The potential therapeutic application of Zn-2Cu-0.5Zr in senile osteoporotic fracture was tested using a rat model of age-related osteoporosis. The Zn-2Cu-0.5Zr alloy met the requirements for load-bearing applications and accelerated the healing process in a tibial fracture in aged rats. The imaging and histological analyses showed that it could accelerate the bone-repair process and promote the fracture healing in senile osteoporotic rats. These findings suggest that the novel Zn-2Cu-0.5Zr alloy holds potential for influencing the immunomodulatory function of macrophages and facilitating bone repair in elderly individuals with osteoporosis.
PubMed: 38770427
DOI: 10.1016/j.bioactmat.2024.05.003 -
Frontiers in Medicine 2024Osteoporotic vertebral compression fractures (OVCF) appear to be more common as the population ages. Previous studies have found that percutaneous vertebroplasty (PVP)...
Long-term outcome of percutaneous vertebroplasty versus conservative treatment for osteoporotic vertebral compression fractures: a retrospective cohort study with three-year follow-up.
BACKGROUND
Osteoporotic vertebral compression fractures (OVCF) appear to be more common as the population ages. Previous studies have found that percutaneous vertebroplasty (PVP) can achieve better short-term clinical outcomes than conservative treatment (CT) for OVCF. However, the long-term outcomes of PVP compared with CT for OVCF has been rare explored. This study was designed to explore the clinical outcomes of PVP or CT within 3 years after OVCF.
METHODS
This study reviewed the clinical outcomes of patients who underwent PVP or CT for OVCF in a single center from January 2015 to December 2019. The back pain visual analogue scale (VAS), Oswestry disability index (ODI) and satisfaction rate were compared between the two groups at baseline, 1 week, 1 month, 3 months, 6 months, 12 months, 24 months and 36 months after treatment.
OUTCOMES
The baseline data including gender, age, bone mineral density, body mass index, back pain VAS, and ODI were not significantly different between the two groups. The back pain VAS and ODI of CT patients were significantly higher than those of PVP group at 1 week, 1 month, 3 months, 6 months and 12 months after treatment. The satisfaction rate in the PVP group were significantly higher than those in the CT group at 1 week, 1 month, 3 months and 6 months after treatment. Subsequently, the back pain VAS and ODI showed no significant difference between the two groups at 24 and 36 months. In addition, there was no significant difference in treatment satisfaction between the two groups at 36 months. There was no significant difference in the rate of new vertebral compression fractures between the two groups within 36 months after treatment.
CONCLUSION
The clinical outcomes within 12 months after PVP and patient satisfaction rate within 6 months after PVP were significantly higher than CT. However, during 12 months to 36 months, this advantage generated by PVP was gradually diluted over time. Compared with CT, the long-term effect of PVP on OVCF should not be overestimated.
PubMed: 38765251
DOI: 10.3389/fmed.2024.1391243 -
Asian Spine Journal May 2024A retrospective analysis.
STUDY DESIGN
A retrospective analysis.
PURPOSE
To investigate the occurrence of central sensitization (CS) in patients with osteoporotic vertebral compression fractures (OVCFs) and identify the association between CS and residual back pain (RBP).
OVERVIEW OF LITERATURE
RBP is a vexing complication that affects 6.3%-17.0% of patients with OVCFs who underwent percutaneous vertebroplasty (PVP). Given the negative effect of RBP on patients' psychological and physiological statuses, efforts to preoperatively select patients who are at risk for RBP development have a high priority to offer additional treatment and minimize this complication.
METHODS
Preoperatively, all 160 patients with OVCFs underwent pressure-pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and imaging assessments. Pain intensity and pain-related disability were evaluated before and after PVP.
RESULTS
Preoperatively, patients with OVCFs had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy participants (p<0.05). Unlike patients with acute fractures, patients with subacute/chronic OVCFs showed higher TS with or without lower CPM in the pain-free area compared with healthy participants (p<0.05). Postoperatively, RBP occurred in 17 of 160 patients (10.6%). All preoperative covariates with significant differences between the RBP and non-RBP groups were subjected to multivariate logistic regression, showing that intravertebral vacuum cleft, posterior fascia edema, numeric rating pain scale scores for low back pain at rest, and TS were independently associated with RBP (p<0.05).
CONCLUSIONS
Augmented central pain processing may occur in patients with OVCFs, even in the subacute stage, and this preexisting CS may be associated with RBP. Preoperative assessment of TS in pain-free areas may provide additional information for identifying patients who may be at risk of RBP development, which may be beneficial for preventing this complication.
PubMed: 38764226
DOI: 10.31616/asj.2023.0429