Fully automated deep learning system for osteoporosis screening using chest computed tomography images.

Background: Osteoporosis, a disease stemming from bone metabolism irregularities, affects approximately 200 million people worldwide. Timely detection of osteoporosis is pivotal in grappling with this public health challenge. Deep learning (DL), emerging as a promising methodology in the field of medical imaging, holds considerable potential for the assessment of bone mineral density (BMD). This study aimed to propose an automated DL framework for BMD assessment that integrates localization, segmentation, and ternary classification using various dominant convolutional neural networks (CNNs). Methods: In this retrospective study, a cohort of 2,274 patients underwent chest computed tomography (CT) was enrolled from January 2022 to June 2023 for the development of the integrated DL system. The study unfolded in 2 phases. Initially, 1,025 patients were selected based on specific criteria to develop an automated segmentation model, utilizing 2 VB-Net networks. Subsequently, a distinct cohort of 902 patients was employed for the development and testing of classification models for BMD assessment. Then, 3 distinct DL network architectures, specifically DenseNet, ResNet-18, and ResNet-50, were applied to formulate the 3-classification BMD assessment model. The performance of both phases was evaluated using an independent test set consisting of 347 individuals. Segmentation performance was evaluated using the Dice similarity coefficient; classification performance was appraised using the receiver operating characteristic (ROC) curve. Furthermore, metrics such as the area under the curve (AUC), accuracy, and precision were meticulously calculated. Results: In the first stage, the automatic segmentation model demonstrated excellent segmentation performance, with mean Dice surpassing 0.93 in the independent test set. In the second stage, both the DenseNet and ResNet-18 demonstrated excellent diagnostic performance in detecting bone status. For osteoporosis, and osteopenia, the AUCs were as follows: DenseNet achieved 0.94 [95% confidence interval (CI): 0.91-0.97], and 0.91 (95% CI: 0.87-0.94), respectively; ResNet-18 attained 0.96 (95% CI: 0.92-0.98), and 0.91 (95% CI: 0.87-0.94), respectively. However, the ResNet-50 model exhibited suboptimal diagnostic performance for osteopenia, with an AUC value of only 0.76 (95% CI: 0.69-0.80). Alterations in tube voltage had a more pronounced impact on the performance of the DenseNet. In the independent test set with tube voltage at 100 kVp images, the accuracy and precision of DenseNet decreased on average by approximately 14.29% and 18.82%, respectively, whereas the accuracy and precision of ResNet-18 decreased by about 8.33% and 7.14%, respectively. Conclusions: The state-of-the-art DL framework model offers an effective and efficient approach for opportunistic osteoporosis screening using chest CT, without incurring additional costs or radiation exposure.

Fast dual-echo estimation of apparent long T2 fraction using ultrashort echo time magnetic resonance imaging in tibialis tendons and its osteoporosis-related differences in women.

Background: Tendon and bone comprise a critical interrelating unit. Bone loss, including that seen with osteopenia (OPe) or osteoporosis (OPo), may be associated with a reduction in tendon quality, though this remains incompletely investigated. Clinical magnetic resonance imaging (MRI) sequences cannot directly detect signals from tendons because of the very short T2. Clinical MRI may detect high-graded abnormalities by changes in the adjacent structures like bone. However, ultrashort echo time MRI (UTE-MRI) can capture high signals from all tendons. To determine if the long T2 fraction, as measured by a dual-echo UTE-MRI sequence, is a sensitive quantitative technique to the age- and bone-loss-related changes of the lower leg tendons. Methods: This is a cross-sectional study conducted between January 2018 to February 2020 in the lower legs of 14 female patients with OPe [72±6 years old, body mass index (BMI) =25.8±6.2 kg/m2] and 31 female patients with OPo (73±6 years old, BMI=22.0±3.8 kg/m2), as well as 30 female subjects with normal bone (Normal, 35±18 years old, BMI =23.2±4.3 kg/m2), were imaged on a 3T clinical scanner using a dual-echo 3D Cones UTE sequence. We defined the apparent long T2 signal fraction (aFrac-LongT2) of tendons as the ratio between the signal at the second echo time (TE =2.2 ms) to the UTE signal. The average aFrac-LongT2 and the cross-sectional area were calculated for the anterior tibialis tendons (ATTs) and the posterior tibialis tendons (PTTs). The Kruskal-Wallis rank test was used to compare the differences in aFrac-LongT2 and the cross-sectional area of the tendons between the groups. Results: The aFrac-LongT2 of the ATTs and PTTs were significantly higher in the OPo group compared with the Normal group (22.2% and 34.8% in the ATT and PTT, respectively, P<0.01). The cross-sectional area in the ATTs was significantly higher for the OPo group than in the Normal group (Normal/OPo difference was 28.7, P<0.01). Such a difference for PTTs did not reach the significance level. Mean aFrac-LongT2 and cross-sectional area in the OPe group were higher than the Normal group and lower than the OPo group. However, the differences did not show statistical significance, likely due to the higher BMI in the OPe group. Conclusions: Dual-echo UTE-MRI is a rapid quantification technique, and aFrac-LongT2 values showed significant differences in tendons between Normal and OPo patients.

Quantitative analysis of mandibular cortical morphology using artificial intelligence-based computer assisted diagnosis for panoramic radiography on underlying diseases and dental status in women over 20 years of age.

Background/purpose: Recently, an artificial intelligence-based computer-assisted diagnosis (AI-CAD) for panoramic radiography was developed to scan the inferior margin of the mandible and automatically evaluate mandibular cortical morphology. The aim of this study was to analyze quantitatively the mandibular cortical morphology using the AI-CAD, especially focusing on underlying diseases and dental status in women over 20 years of age. Materials and methods: 419 patients in women over 20 years of age who underwent panoramic radiography were included in this study. The mandibular cortical morphology was analyzed with an AI-CAD that evaluated the degree of deformation of the mandibular inferior cortex (MIC) and mandibular cortical index (MCI) automatically. Those were analyzed in relation to underlying diseases, such as diabetes, hypertension, dyslipidemia, rheumatism and osteoporosis, and dental status, such as the number of teeth present in the maxilla and mandible. Results: The degree of deformation of MIC in women under 51 years of age (21-50 years; n = 229, 16.0 ± 12.7) was significantly lower than those of over 50 years of age (51-90 years; n = 190, 45.1 ± 23.0), and the MCI was a significant difference for the different age group. Regarding the degree of deformation of MIC and MCI in women over 50 years of age, osteoporosis and number of total teeth present in the maxilla and mandible were significant differences. Conclusion: The results of this study indicated that the mandibular cortical morphology using the AI-CAD is significantly related to osteoporosis and dental status in women over 50 years of age.

Long-term follow-up after vertebroplasty - A mean 10-years follow-up control study.

Objectives: To evaluate the clinical 10 year outcome of patients treated with percutaneous vertebroplasty for vertebral compression fractures and to determine the incidence of new fractures in this time interval, as well as the mortality of the patients who underwent this procedure. Methods: All patients undergoing vertebroplasty for vertebral compression fractures between May 2007 until July 2008 were prospectively followed up at 10 years postoperatively. Patients were assessed for radiologic outcome and self-reported outcome parameters (PROs). Gathered parameters remained unmodified to the initial ones analyzing QoL improvement (EQ5D 3L and NASS score) and pain alleviation (VAS, NRS). Mortality was defined as an additional endpoint. Exclusion criteria include additional instrumentation, use of additional devices such as kyphoplasty balloons/stentoplasty, cognitive impairment, insufficient radiological documentation or absent re-consent. Results: Of 280 patients who underwent vertebroplasty, 49 (17.5%) were available for re-assessment with a mean follow-up of 10.5 years (9.9-11.1). Thirty patients (10.7%) were assessed clinically and radiologically, 16 (5.7%) in written form and three (1.1%) by phone only. A total of 186 (66.4%) died during the follow up period. Out of the remaining 45 patients, 27 patients declined participation, eight couldn't participate due to cognitive impairment, four had insufficient radiologic documentation. Six patients were lost to follow-up. At 10 years, patients reported a consistently improved quality of life (EQ-5D; p < 0.01) and global satisfaction. Vertebroplasty demonstrated a substantial and enduring effect on alleviating back pain over 10 years (p < 0.001). 26 (53%) patients experienced a new fracture since the initial procedure. Conclusion: A decade following vertebroplasty, patients continue to demonstrate a quality of life and pain level comparable to short and medium-term assessments, with a significant difference from baseline measurements. More than half (53%) of the patients participating at last follow-up experienced new fractures during this interim period. The cohort as a whole has been impacted by an elevated mortality rate over the time period.

Knowledge, Attitude, and Practices Towards Osteoporosis Among Adults in the United Arab Emirates (UAE) in 2023.

BACKGROUND: Osteoporosis, the silent epidemic, is defined as a systemic skeletal disease characterized by low mineral bone mass and micro-architectural deterioration of bone tissue. Osteoporosis is considered a burden to global economic, social, and health development. Osteoporosis exerts a substantial global influence, markedly influencing rates of illness and death on a broad scale. Clinical features of osteoporosis can include chronic back pain, loss of height, and a stooped posture, as well as an increased risk of fractures in the spine, hip, and wrist. Accurate identification and monitoring of these clinical features are essential for effective management and treatment of osteoporosis. This study aims to identify the knowledge, attitudes, and practices (KAP) of adults (over 18 years) about osteoporosis and identify relations between knowledge, attitudes, and practices with demographic data. Furthermore, to assess the risk factors and preventive measures for osteoporosis. METHODOLOGY: Data from 446 responders were collected using a Google Forms questionnaire, including questions to assess knowledge, attitudes, and practice levels among adults 18 years and above in the United Arab Emirates (UAE). The collected data and statistical analysis were done through the IBM® SPSS® Statistics. Chi-Square was used in SPSS Statistics; the chi-square test was used for the relation between categorical variables, and P less than 0.05 was the cut-off level of significance. RESULTS: The research revealed that 41.9% of the participants had good knowledge, 38.8% had a positive attitude, and 45.3% had poor practices. The results also showed that there is a statistically significant correlation between gender and knowledge, attitudes, and practices. CONCLUSION: Our research demonstrates that there's a statistically significant correlation between gender variables with knowledge, attitudes, and practices. These findings have important implications in assessing the correlation between variables in our research that could be used to prevent osteoporosis further, target the specific demographic group, and provide the required education. Overall, our research contributes to a better understanding of the knowledge, attitude, and practices towards Osteoporosis among adults in the UAE and underscores the importance of further awareness in this area.

The role of echinacoside-based cross-linker nanoparticles in the treatment of osteoporosis.

Background: Current drugs for treating osteoporosis may lead to toxic side effects. Echinacoside (ECH) is a natural small molecule drug. This study examined and compared the therapeutic effects of cross-linker (CL)-ECH and ECH-free nanoparticles on osteoporosis. Methods: Echinocandin-based CL-ECH nanoparticles were prepared, and the nanoparticle size and drug loading were optimized and characterized by adjusting the ratio. The antioxidant effect of CL-ECH nanoparticles on bone marrow-derived macrophages (BMDMs) was analyzed using flow cytometry, immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR). Bone marrow stromal cells (BMSCs)-based detection of bone-producing effects was conducted using alkaline phosphatase (ALP), Alizarin Red S (ARS) and qRT-PCR. TRAP, phalloidin staining, and qRT-PCR was performed to detect osteogenesis-inhibiting effect on BMDMs. CL-ECH nanoparticles were applied to treat an ovariectomized (OVX) mouse model at low doses. Results: Compared to ECH, CL-ECH nanoparticles suppressed oxidative stress in BMDMs by promoting NRF-2 nuclear translocation, which inhibited the production of both reactive oxygen species (ROS) and osteoclast production through downregulating NF-κB expression, with limited effect on the osteogenesis of BMSCs. In vivo studies showed that low-dose CL-ECH nanoparticles markedly improved bone trabecular loss compared to ECH administration in the treatment of osteoporosis. Conclusions: The current discoveries provided a solid theoretical foundation for the development of a new generation of anti-bone resorption drugs and antiosteoporosis drugs.

Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism.

Osteoporosis (OP) is a severe global health issue that has significant implications for productivity and human lifespan. Gut microbiota dysbiosis has been demonstrated to be closely associated with OP progression. Melatonin (MLT) is an important endogenous hormone that modulates bone metabolism, maintains bone homeostasis, and improves OP progression. Multiple studies indicated that MLT participates in the regulation of intestinal microbiota and gut barrier function. However, the promising effects of gut microbiota-derived MLT in OP remain unclear. Here, we found that OP resulted in intestinal tryptophan disorder and decreased the production of gut microbiota-derived MLT, while administration with MLT could mitigate OP-related clinical symptoms and reverse gut microbiota dysbiosis, including the diversity of intestinal microbiota, the relative abundance of many probiotics such as Allobaculum and Parasutterella, and metabolic function of intestinal flora such as amino acid metabolism, nucleotide metabolism, and energy metabolism. Notably, MLT significantly increased the production of short-chain fatty acids and decreased trimethylamine N-oxide-related metabolites. Importantly, MLT could modulate the dynamic balance of M1/M2 macrophages, reduce the serum levels of pro-inflammatory cytokines, and restore gut-barrier function. Taken together, our results highlighted the important roles of gut microbially derived MLT in OP progression via the "gut-bone" axis associated with SCFA metabolism, which may provide novel insight into the development of MLT as a promising drug for treating OP.

Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis.

Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention.

Rapid Selenoprotein Activation by Selenium Nanoparticles to Suppresses Osteoclastogenesis and Pathological Bone Loss.

Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species (ROS) emerges as a viable approach in addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys2) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly those derived from lentinan (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys2, the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of RANKL-induced osteoclastogenesis and osteoclastic activity when compared to alternative Se species. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys2, potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over macrophage polarization, osteoclast activity inhibition, and the prevention of CIA/OVX-induced osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1 to re-polarize macrophages. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders, with considerable potential for clinical translation. This article is protected by copyright. All rights reserved.

Changes in bone mineral density in patients with non-dialysis dependent chronic kidney disease are associated with body composition.

OBJECTIVE: Chronic kidney disease (CKD) and low bone mineral density (BMD) are highly prevalent and can co-exist. Parameters of mineral metabolism are associated with BMD in CKD, but other contributing factors may contribute. The aim of this study was to assess changes in BMD and its determinants in patients with non-dialysis-dependent CKD (NDD-CKD). METHODS: Body composition and biochemical profiles were assessed in a retrospective hospital-based cohort study of patients with NDD-CKD. BMD, lean soft tissue (LST), appendicular LST (ALST), and percentage fat mass were assessed by dual-energy X-ray absorptiometry (DXA). ALST index (ALSTI, ALST/height2) and load-capacity index (LCI, fat mass/LST) were calculated. Low BMD was defined as t-score ≤-1.0. RESULTS: Mean time between assessments was 2.8±1.3 years, 46 patients were included. A reduction in renal function was observed. Changes in body composition included reductions in ALST (p=0.031), ALSTI (p=0.021) and a trend for BMD (p=0.053); and an increase in percentage fat mass (p=0.044) and LCI (p=0.032). Females had a reduction in BMD (p=0.034), ALST (p=0.026), and ALSTI (p=0.037). Patients with low BMD at baseline had lower LST (p=0.013), ALST (p=0.023), and percentage fat mass (p=0.037) than those with normal BMD. Additionally, reductions in LST (p=0.041), ALST (p=0.006), and ALSTI (p=0.008) were observed in patients who had low BMD at baseline, while no significant changes in body composition were observed in those with normal BMD at baseline. The following body composition parameters at baseline were determinants of BMD status at follow-up: LST (OR:0.899, 95%CI:0.829-0.976, p=0.010), ALST (OR:0.825, 95%CI:0.704-0.967, p=0.017), and ALSTI (OR:0.586, 95%CI:0.354-0.968, p=0.037), independent of fat mass, and LCI. CONCLUSIONS: Detrimental body composition changes were observed without changes in body weight; these were more significant in females. Moreover, this is the first longitudinal study showing a protective effect of LST against BMD loss in patients with NDD-CKD.

Mijiao formula regulates NAT10-mediated Runx2 mRNA ac4C modification to promote bone marrow mesenchymal stem cell osteogenic differentiation and improve osteoporosis in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mijiao (MJ) formula, a traditional herbal remedy, incorporates antlers as its primary constituent. It can effectively treat osteoporosis (OP), anti-aging, enhance immune activity, and change depression-like behavior. In this study, we investigated that MJ formula is a comprehensive treatment strategy, and may provide a potential approach for the clinical treatment of postmenopausal osteoporosis. AIM OF THE STUDY: The purpose of this study was to determine whether MJ formula promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and improved osteoporosis in ovariectomized rats by regulating the NAT10-mediated Runx2 mRNA ac4C modification. MATERIALS AND METHODS: Female Sprague-Dawley (SD) rats were used to investigate the potential therapeutic effect of MJ formula on OP by creating an ovariectomized (OVX) rat model. The expression of osteogenic differentiation related proteins in BMSCs was detected in vivo, indicating their role in promoting bone formation. In addition, the potential mechanism of its bone protective effect was explored via in vitro experiments. RESULTS: Our study showed that MJ formula significantly mitigated bone mass loss in the OVX rat model, highlighting its potential as an OP therapeutic agent. We found that the possible mechanism of action was the ability of this formulation to stabilize Runx2 mRNA through NAT10-mediated ac4C acetylation, which promoted osteogenic differentiation of BMSCs and contributed to the enhancement of bone formation. CONCLUSIONS: MJ formula can treat estrogen deficiency OP by stabilizing Runx2 mRNA, promoting osteogenic differentiation and protecting bone mass. Conceivably, MJ formulation could be a safe and promising strategy for the treatment of osteoporosis.

Family/caregiver influence on osteoporosis management for older people: an integrative review.

An integrative literature review was conducted to understand family/caregiver influence on osteoporosis management for older people. Findings include caregivers' overprotection, caregivers' risks for fragility fractures due to caregiving role, poor bone health in caregivers, and caregivers' burden and facilitators. Caregivers should be included in bone health and discharge planning. Literature on family/caregiver influence on osteoporosis management for older people is sparse. Older people are prone to osteoporosis and fragility fractures due to their age, often triggering the need for a caregiver after experiencing a fragility fracture. These fractures pose significant costs to the patient and health systems and are projected to increase with the aging population. This study applied an integrative literature review methodology to key literature findings on family/caregiver influence on osteoporosis management for older people. Key findings include caregivers' tendency to overprotect persons who experience hip fracture by limiting mobilization, thus impeding recovery, caregivers' risks for their own fragility fractures due to the demands of their caregiving role, risks of poor bone health in caregivers, and caregivers' experience of significant burden for which facilitators have been identified. Family caregivers of older people with osteoporosis have unique needs and require support and resources, especially after their loved one experiences a hip fracture. Informal caregivers must be considered in bone health education and discharge planning. They should be considered in the creation of osteoporosis guidelines and within the work of fracture liaison services. More research is needed to increase understanding about family caregiver influence on osteoporosis management.

Does the outcome of graft materials at dental implant sites differ between patients with normal and compromised bone health?

OBJECTIVE: To assess the outcome of bone graft material at alveolar bone augmentation sites combined with dental implants in postmenopausal women with compromised bone health by evaluating cone beam computed tomography (CBCT) scans at multiple time points. MATERIALS AND METHODS: CBCT scans were analyzed on 55 postmenopausal women with compromised bone health status to determine the fate of alveolar bone augmentation. CBCT scans were taken immediately after surgery and 9 and 24 months post-operatively. The patient's medication regimens and durations were recorded, and the pixel intensity value (PIV) was measured and standardized using scoring criteria and visual assessment. Statistical analyses included two-sample t-tests for continuous variables and Fisher's exact tests for categorical variables. RESULTS: Among the normal patients, 73% received a grade 2 visual score, and 27% received a grade 1 visual score. After 24 months, 45% of patients received a grade 2 score, and 27% received a grade 3 score. In the osteoporotic group receiving medication, 77% of participants received a grade 1 visual score at the 9-month postoperative evaluation, while 23% received a grade 2 score. At the 24-month assessment, 55% of patients received a grade 1 score, 41% received a grade 2 score, and only 5% received a grade 3 score. Notably, although the graft material did not remodel into native bone, it was a scaffold for implants in controlled osteoporotic patients. CONCLUSION: The study's results show that the pixel intensity values of particulate graft materials are similar across the three different time points, suggesting that the graft material's pixel intensity value remains constant in postmenopausal women with osteoporosis. The study's limitations include a small sample size and a restricted 24-month follow-up period. This limited time frame may need to capture long-term changes or variations in graft materials adequately. FUTURE DIRECTIONS: Future research should include a larger sample size and have a longer follow-up duration to provide a more comprehensive understanding of the change in graft materials between patients with normal and compromised bone health.

Assessment of causal association between the socio-economic status and osteoporosis and fractures: a bidirectional Mendelian randomization study in European population.

BACKGROUND: The relationship between socio-economic status and bone-related diseases is attracting increasing attention. Therefore, a bidirectional Mendelian randomization (MR) analysis was performed in this study. METHODS: Genetic data on factors associated with socio-economic status (average total household income before tax, years of schooling completed and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fracture (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses, and multivariable MR was performed to enhance the robustness of our findings. RESULTS: A higher educational attainment was associated with an increased level of eBMD (beta:0.06, 95% CI:0.01-0.10, P = 7.24 × 10-3), and decreased risk of osteoporosis (OR:0.78, 95% CI:0.65-0.94, P = 8.49 × 10-3), spine fracture (OR:0.76, 95% CI:0.66-0.88, P = 2.94 × 10-4), femur fracture (OR:0.78, 95% CI:0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR:0.79, 95% CI:0.70-0.88, P = 2.05 × 10-5), foot fracture (OR:0.78, 95% CI:0.66-0.93, P = 5.92 × 10-3) and wrist-hand fracture (OR:0.83, 95% CI:0.73-0.95, P = 7.15 × 10-3). Further, material deprivation seemed to harm the spine fracture (OR:2.63, 95% CI:1.43-4.85, P = 1.91 × 10-3). A higher level of FN-BMD positively affected increased household income (beta:0.03, 95% CI:0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index (BMI), type 2 diabetes, smoking initiation, and frequency of alcohol intake. CONCLUSIONS: The Mendelian randomization analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings offer valuable insights into the formulation of health guidelines and policy development.

We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.

Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass.

Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. PURPOSE: Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. METHODS: Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. RESULTS: Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. CONCLUSION: This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.

Assessing osteoporosis in postmenopausal women: preliminary results using a novel lumbar spine phantom-based MRI scoring method.

OBJECTIVE: To develop a novel magnetic resonance imaging (MRI) phantom for producing F-score (for fat) and W-score (for water) and to evaluate the performance of these scores in assessing osteoporosis and related vertebral fractures. MATERIALS AND METHODS: First, a real-time phantom consisting of oil and water tubes was manufactured. Then, 30 female volunteers (age: 62.3 ± 6.3 years) underwent lumbar spine examination with MRI (using a novel phantom) and dual-energy X-ray absorptiometry (DXA), following ethical approval. MRI phantom-based F-score and W-score were defined by normalizing the vertebral signal intensities (SIs) by the oil and water SIs of the phantom on T1- and T2-weighted images, respectively. The diagnostic performances of the new scores for assessing osteoporosis and vertebral fractures were examined using receiver operating characteristic analysis and compared with DXA-measured areal bone mineral density (DXA-aBMD). RESULTS: The F-score and W-score were greater in the osteoporotic patients (3.93 and 2.29) than the non-osteoporotic subjects (3.05 and 1.79) and achieved AUC values of 0.85 and 0.74 (p < 0.05), respectively, when detecting osteoporosis. Similarly, F-score and W-score had greater values for the fracture patients (3.94 and 2.53) than the non-fracture subjects (3.14 and 1.69) and produced better AUC values (0.90 for W-score and 0.79 for F-score) compared to DXA-aBMD (AUC: 0.27, p < 0.05). In addition, the F-score and W-score had a strong correlation (r = 0.77; p < 0.001). CONCLUSION: A novel real-time lumber spine MRI phantom was developed, based upon which newly defined F-score and W-score were able to detect osteoporosis and demonstrated an improved ability over DXA-aBMD in differentiating patients with vertebral fractures.

Capacitive biophysical stimulation improves the healing of vertebral fragility fractures: a prospective multicentre randomized controlled trial.

BACKGROUND: Capacitively coupling electric fields (CCEF) is a method of non-invasive biophysical stimulation that enhances fracture repair and spinal fusion. This multicentre randomized controlled trial aimed to further examine the roles of CCEF in (1) the resolution of vertebral bone marrow oedema (VBME) using a follow-up MRI study and (2) pain relief, analgesic drug consumption and quality of life improvement in stimulated patients who were referred with acute vertebral fragility fractures (VFFs) compared to non-stimulated patients. METHODS: Between September 2016 and December 2019, patients who were referred to the spine centres that participated in this multicentre randomized clinical study with acute VFFs of type OF1 or OF2 were included in the present study. All the VFFs were conservatively managed according to Good Clinical Practice. Moreover, the patients were randomized into two groups: the CCEF group received, as an adjunct to the clinical study protocol, biophysical stimulation with a CCEF device (Osteospine, IGEA) for 8 h per day for 60 days, whereas the control group was treated according to the clinical study protocol. At baseline (T0), the 30-day follow-up (T1), the 60-day follow-up (T2), and the 6-month follow-up (T3), each patient underwent clinical evaluation using the Visual Analogue Scale (VAS) for Pain and the Oswestry Disability Index (ODI). Analgesic therapy with paracetamol 1000 mg tablets for 7 days-or longer, depending on the pain intensity-was performed; patients were required to report their paracetamol consumption on a specific sheet between study day 8 to 180 days of follow-up. MRI studies of the thoracolumbar spine were performed at 0 (T0), 30 (T1) and 60 days of follow-up (T2) using a 1.5-T MRI system in all of the centres that took part in the study. For each VBME area examined via MRI, the vertebral body geometry (i.e. anterior wall height/posterior wall height and vertebral kyphosis) were assessed. RESULTS: A total of 66 patients (male: 9, 13.63%; mean age: 73.15 years old) with 69 VFFs were included in the present study and randomized as follows: 33 patients were included in the control group and the remaining 33 patients were randomized into the CCEF group. In the CCEF group, good compliance with CCEF therapy was observed (adherence = 94%), and no adverse effects were recorded. In the stimulated patients, faster VBME resolution and significantly less vertebral body collapse during follow-up were observed compared to the control patients. Moreover, in the active group, faster pain reduction and improvement in the ODI mean score were observed. Stimulated patients also reported a significantly lower paracetamol consumption rate from the third follow-up after treatment until the 6-month follow-up. In terms of sex-related differences, in the CCEF group, VBME showed a faster resolution in male patients compared with females. CONCLUSION: Biophysical stimulation with CCEF, as an adjunct to traditional conservative treatment, is a useful tool to hasten the VBME resolution process and prevent vertebral body deformation. These MRI findings also correlate with faster back pain resolution and quality of life improvement. From the third follow-up after treatment until the 6-month follow-up, stimulated patients reported a significantly lower paracetamol consumption than control patients, even though back pain and quality of life showed no significant differences between the two groups. LEVEL OF EVIDENCE: II. Trial Registration Register: ClinicalTrials.gov, number: NCT05803681.

Chitosan modified with PAP as a promising delivery system for melatonin in the treatment of osteoporosis: targeting the divalent metal transporter 1.

The demands for novel and efficient therapies have gradually increased with the rising concerns of osteoporosis (OP). The most popular method in promoting bone regeneration during osteoporotic conditions consists of loading bioactive materials with different drugs to treat osteoporotic bones by either promoting the process of osteogenesis, or by inhibiting the activity of osteoclasts. By analyzing single cell sequencing results, we found that divalent metal transporter 1 (DMT1) played a role in OP. Based on our previous results, we found that melatonin (MT) suppressed expression of DMT1 induced by high glucose during OP, so we determined the efficacy of MT for the treatment of OP. However, the clinical effects of MT on OP were unsatisfactory. To enhance its biological efficacy, we combined MT with porous gelatin chitosan (chitosan) and the conductive material, PLA-b-AP-b-PLA (PAP), then determined how MT incorporation in chitosan@PAP nanoparticles affected the ability to promote MC3T3-E1 osteogenesis and mineralization, both in vitro and in vivo. The results confirmed the effect of MT on DMT1. We then prepared and characterized composites prepared as nanofibers, and determined the efficacy of MT combined with chitosan-PAP modified hydrogels as a slow-release system in a femur model of osteoporosis mice, with associated properties suitable for bone tissue engineering. The results indicated that MT-loaded chitosan@PAP nanospheres showed favorable osteogenic functions, both in vivo and in vitro, providing a practical solution for bone regeneration for OP patients.

Cinnamaldehyde attenuates streptozocin-induced diabetic osteoporosis in a rat model by modulating netrin-1/DCC-UNC5B signal transduction.

Background: Cinnamaldehyde (CMD) is a major functional component of Cinnamomum verum and has shown treatment effects against diverse bone diseases. This study aimed to assess the anti-diabetic osteoporosis (DOP) potential of diabetes mellitus (DM) and to explore the underlying mechanism driving the activity of CMD. Methods: A DOP model was induced via an intraperitoneal injection of streptozocin (STZ) into Sprague-Dawley rats, and then two different doses of CMD were administered to the rats. The effects of CMD on the strength, remodeling activity, and histological structure of the bones were assessed. Changes in the netrin-1 related pathways also were detected to elucidate the mechanism of the anti-DOP activity by CMD. Results: CMD had no significant effect on the body weight or blood glucose level of the model rats. However, the data showed that CMD improved the bone strength and bone remodeling activity as well as attenuating the bone structure destruction in the DOP rats in a dose-dependent manner. The expression of netrin-1, DCC, UNC5B, RANKL, and OPG was suppressed, while the expression of TGF-ß1, cathepsin K, TRAP, and RANK was induced by the STZ injection. CMD administration restored the expression of all of these indicators at both the mRNA and protein levels, indicating that the osteoclast activity was inhibited by CMD. Conclusion: The current study demonstrated that CMD effectively attenuated bone impairments associated with DM in a STZ-induced DOP rat model, and the anti-DOP effects of CMD were associated with the modulation of netrin-1/DCC/UNC5B signal transduction.

Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity.

Osteoporosis characterized by decreased bone density and mass, is a systemic bone disease with the destruction of microstructure and increase in fragility. Osteoporosis is attributed to multiple causes, including aging, inflammation, diabetes mellitus, and other factors induced by the adverse effects of medications. Without treatment, osteoporosis will further progress and bring great trouble to human life. Due to the various causes, the treatment of osteoporosis is mainly aimed at improving bone metabolism, inhibiting bone resorption, and promoting bone formation. Although the currently approved drugs can reduce the risk of fragility fractures in individuals, a single drug has limitations in terms of safety and effectiveness. By contrast, traditional Chinese medicine (TCM), a characteristic discipline in China, including syndrome differentiation, Chinese medicine prescription, and active ingredients, shows unique advantages in the treatment of osteoporosis and has received attention all over the world. Therefore, this review summarized the pathogenic factors, pathogenesis, therapy limitations, and advantages of TCM, aiming at providing new ideas for the prevention and treatment of OP.