[Osteoporosis-Definition, risk assessment, diagnosis, prevention and treatment (update 2024) : Guidelines of the Austrian Society for Bone and Mineral Research]. / Osteoporose ­ Definition, Risikoerfassung, Diagnose, Prävention und Therapie (Update 2024) : Leitlinie der Österreichischen Gesellschaft für Knochen- und Mineralstoffwechsel.

BACKGROUND: Austria is among the countries with the highest incidence and prevalence of osteoporotic fractures worldwide. Guidelines for the prevention and management of osteoporosis were first published in 2010 under the auspices of the then Federation of Austrian Social Security Institutions and updated in 2017. The present comprehensively updated guidelines of the Austrian Society for Bone and Mineral Research are aimed at physicians of all specialties as well as decision makers and institutions in the Austrian healthcare system. The aim of these guidelines is to strengthen and improve the quality of medical care of patients with osteoporosis and osteoporotic fractures in Austria. METHODS: These evidence-based recommendations were compiled taking randomized controlled trials, systematic reviews and meta-analyses as well as European and international reference guidelines published before 1 June 2023 into consideration. The grading of recommendations used ("conditional" and "strong") are based on the strength of the evidence. The evidence levels used mutual conversions of SIGN (1++ to 3) to NOGG criteria (Ia to IV). RESULTS: The guidelines include all aspects associated with osteoporosis and osteoporotic fractures, such as secondary causes, prevention, diagnosis, estimation of the 10-year fracture risk using FRAX®, determination of Austria-specific FRAX®-based intervention thresholds, drug-based and non-drug-based treatment options and treatment monitoring. Recommendations for the office-based setting and decision makers and institutions in the Austrian healthcare system consider structured care models and options for osteoporosis-specific screening. CONCLUSION: The guidelines present comprehensive, evidence-based information and instructions for the treatment of osteoporosis. It is expected that the quality of medical care for patients with this clinical picture will be substantially improved at all levels of the Austrian healthcare system.

Single-cell RNA transcriptomics reveals Du-Zhong-Wan promotes osteoporotic fracture healing via YAP/ß-catenin/VEGF axis in BMSCs.

BACKGROUND: Our previous study demonstrated that Du-Zhong-Wan (DZW) promoted osteoporotic fracture (OPF) healing by enhancing osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and angiogenesis of endothelial cells (ECs). However, the heterogeneity of BMSCs and ECs, as well as the specific molecular mechanism underlying these effects, still require further evaluation. PURPOSE: The primary objective of this study was to elucidate the heterogeneity of BMSCs and ECs, as well as the cellular-level mechanism of DZW against OPF through single-cell RNA sequencing. METHODS: In this study, we presented a single-cell atlas of mouse femoral callus, comparing samples with and without DZW treatment, utilizing single-cell RNA sequencing. Variable genes were identified using the FindVariableGenes (FVG) and principal component analysis (PCA) analysis. Additionally, uniform manifold approximation and projection (U-MAP) was employed to reduce and visualize the distinct subclusters. The CellPhoneDB2 method was employed to analyze intercellular communication and quantify the interaction between ligands and receptors within distinct cell clusters. The osteogenic differentiation capacity of BMSCs was assessed by micro-CT, alkaline phosphatase (ALP), and alizarin red S (ARS) assay. The scratch wound assay and tube formation assay were utilized to assess the angiogenic capabilities of ECs in vitro. Additionally, western blot and immunofluorescence experiments were utilized to elucidate the related protein expression. RESULTS: Consistent with our previous studies, DZW obviously promoted osteoporotic fracture healing. Moreover, this study discovered 14 cell clusters at the femoral fracture callus, where the BMSCs most actively interacted with ECs, through single-cell sequencing. Notably, DZW significantly elevated the proportion of Lepr+ BMSCs and Podxl+ ECs subgroup, which were respectively considered essential cells for osteoblastogenesis and angiogenesis of arteriolar vessels. The increased proportion of Podxl+ ECs was partially attributed to vascular endothelial growth factor (VEGF), secreted by BMSCs, which were able to be reversed by YAP pharmacological inhibitor verteporfin. Furthermore, the western blot assay revealed elevated expression levels of YAP/ß-catenin, VEGF, RUNX2, and OCN in BMSCs treated with DZW, which were counteracted by verteporfin. CONCLUSION: The data above indicates that DZW elevates the proportion of LEPR+ BMSCs and Podxl+ ECs, therefore contributing for the osteogenic ability of BMSCs and BMSCs-mediated angiogenesis via activation of the YAP/ß-catenin/VEGF axis, which provides novel potential targets and mechanism for DZW in treating OPF in sub-clusters and molecular level.

Integrated model of secondary fracture prevention in primary care (INTERCEPT): protocol for a cluster randomised controlled multicentre trial.

BACKGROUND: Osteoporotic fractures signal severely compromised bone strength and are associated with a greatly increased risk of refracture. Despite the availability of effective and safe medications that reduce fracture risk, 70-80% of patients are inadequately investigated or treated for osteoporosis following an initial fracture, constituting a significant 'osteoporosis care gap'. Optimal methods of bridging this gap with primary care at the forefront of secondary fracture prevention remain undetermined. This protocol describes a cluster randomised controlled trial to evaluate the effectiveness of a novel integrated model of secondary fracture prevention and management in primary care. METHODS: The cluster randomised controlled trial involves multiple branches of a community-based radiology provider (CRP), a hospital-based secondary fracture prevention program (SFPP) and numerous primary care practices in metropolitan Sydney that refer to either the CRP or SFPP. Using natural language processing tools, patients diagnosed with a potential osteoporotic fracture will be identified by automatically screening radiology reports generated at the CRP or SFPP. The primary care practices that these patients attend will be randomised (1:1) to either the intervention or usual care. The intervention consists of (i) electronic and fax alerts informing the practice/primary care physician that their patient has been diagnosed with a potential osteoporotic fracture; (ii) provision of osteoporosis management guidelines and (iii) follow-up surveys at 4 weeks and 6 months. Practices in the usual care (control) group will receive no alerts and provide usual care. The primary outcome is the proportion of patients undergoing a bone density scan and/or filling a prescription for osteo-protective pharmacotherapy within 3 months of the initial diagnostic imaging report. Secondary outcomes are the proportion of patients: (i) undergoing an osteoporosis-related blood test within 3 months of the initial diagnostic imaging report; (ii) initiated on a chronic disease management plan within 3 months of the diagnostic report, and (iii) filling a second prescription for osteo-protective pharmacotherapy within 9 months post initial diagnostic imaging report. Outcomes will be obtained through de-identified linked data from Medical Benefits Schedule and Pharmaceutical Benefits Scheme held by the Australian Institute of Health and Welfare. DISCUSSION: This is the first randomised trial to integrate case-detection of potential osteoporotic fractures in a hospital and community setting with direct alerts to the patient's primary care provider. This study will determine whether such an intervention is effective in improving investigation and/or treatment rates of osteoporosis in patients with a potential osteoporotic fracture. TRIAL REGISTRATION: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000658617p.

SrHPO4-coated Mg alloy implant attenuates postoperative pain by suppressing osteoclast-induced sensory innervation in osteoporotic fractures.

Osteoporotic fractures have become a common public health problem and are usually accompanied by chronic pain. Mg and Mg-based alloys are considered the next-generation orthopedic implants for their excellent osteogenic inductivity, biocompatibility, and biodegradability. However, Mg-based alloy can initiate aberrant activation of osteoclasts and modulate sensory innervation into bone callus resulting in postoperative pain at the sequential stage of osteoporotic fracture healing. Its mechanism is going to be investigated. Strontium hydrogen phosphate (SrHPO4) coating to delay the Mg-based alloy degradation, can reduce the osteoclast formation and inhibit the growth of sensory nerves into bone callus, dorsal root ganglion hyperexcitability, and pain hypersensitivity at the early stage. Liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis of bone marrow-derived macrophages (BMMs) treated with SrHPO4-coated Mg alloy extracts shows the potential effect of increased metabolite levels of AICAR (an activator of the AMPK pathway). We demonstrate a possible modulated secretion of AICAR and osteoclast differentiation from BMMs, which inhibits sensory innervation and postoperative pain through the AMPK/mTORc1/S6K pathway. Importantly, supplementing with AICAR in Mg-activated osteoclasts attenuates postoperative pain. These results suggest that Mg-induced postoperative pain is related to the osteoclastogenesis and sensory innervation at the early stage in the osteoporotic fractures and the SrHPO4 coating on Mg-based alloys can reduce the pain by upregulating AICAR secretion from BMMs or preosteoclasts.

Current status of postoperative care for elderly osteoporotic fracture patients in Jiangsu Province, China: A multicenter cross-sectional study.

BACKGROUND: The postoperative care behavior of elderly osteoporotic fracture patients has a significant impact on their prognosis and rehabilitation; thus, it is critical to completely comprehend their current state of care before optimizing postoperative care strategies. AIMS: To determine the current status of postoperative care for elderly osteoporotic fracture patients in Jiangsu Province. METHODS: From October to December 2023, 669 elderly postoperative patients with osteoporotic fractures were recruited for a cross-sectional study via convenience sampling and a self-designed questionnaire from 21 hospitals in seven urban areas in Jiangsu Province. RESULTS: A total of 800 questionnaires were distributed, and 709 questionnaires were recovered, for a return rate of 88.6%. The postoperative support and care received by the patients were mostly by their children and spouses, and the postoperative health education knowledge received by the patients was mostly about fracture-related knowledge and precautions for the use of medications. Health education methods were mainly conducted by medical staff explanations and health brochures; only 45.3% of the patients were treated with anti-osteoporosis therapy. CONCLUSIONS: The current status of postoperative care for osteoporotic fracture patients in Jiangsu Province varies somewhat according to geographic location, hospital level and other factors, with tertiary hospitals and more economically developed areas having relatively better care outcomes. For in-hospital care, it is necessary to improve the content and methods of in-hospital education. For out-of-hospital care, it is necessary to raise the level of awareness of anti-osteoporosis treatment and the prevention and treatment of re-fractures, and to improve hospital-community referral services.

Subject-level spinal osteoporotic fracture prediction combining deep learning vertebral outputs and limited demographic data.

Automated screening for vertebral fractures could improve outcomes. We achieved an AUC-ROC = 0.968 for the prediction of moderate to severe fracture using a GAM with age and three maximal vertebral body scores of fracture from a convolutional neural network. Maximal fracture scores resulted in a performant model for subject-level fracture prediction. Combining individual deep learning vertebral body fracture scores and demographic covariates for subject-level classification of osteoporotic fracture achieved excellent performance (AUC-ROC of 0.968) on a large dataset of radiographs with basic demographic data. PURPOSE: Osteoporotic vertebral fractures are common and morbid. Automated opportunistic screening for incidental vertebral fractures from radiographs, the highest volume imaging modality, could improve osteoporosis detection and management. We consider how to form patient-level fracture predictions and summarization to guide management, using our previously developed vertebral fracture classifier on segmented radiographs from a prospective cohort study of US men (MrOS). We compare the performance of logistic regression (LR) and generalized additive models (GAM) with combinations of individual vertebral scores and basic demographic covariates. METHODS: Subject-level LR and GAM models were created retrospectively using all fracture predictions or summary variables such as order statistics, adjacent vertebral interactions, and demographic covariates (age, race/ethnicity). The classifier outputs for 8663 vertebrae from 1176 thoracic and lumbar radiographs in 669 subjects were divided by subject to perform stratified fivefold cross-validation. Models were assessed using multiple metrics, including receiver operating characteristic (ROC) and precision-recall (PR) curves. RESULTS: The best model (AUC-ROC = 0.968) was a GAM using the top three maximum vertebral fracture scores and age. Using top-ranked scores only, rather than all vertebral scores, improved performance for both model classes. Adding age, but not ethnicity, to the GAMs improved performance slightly. CONCLUSION: Maximal vertebral fracture scores resulted in the highest-performing models. While combining multiple vertebral body predictions risks decreasing specificity, our results demonstrate that subject-level models maintain good predictive performance. Thresholding strategies can be used to control sensitivity and specificity as clinically appropriate.

Long-Term Bone Density Changes and Fracture Risk in Myasthenia Gravis: Implications for FRAX® Tool Application.

Myasthenia gravis (MG) patients often require long-term glucocorticoid therapy, which may affect bone health. This study aimed to assess long-term changes in bone mineral density (BMD), evaluate osteoporotic fracture incidence, and examine the relationship between MG-specific factors and bone health outcomes over a 10-year period. This single-center, prospective cohort study included 28 MG patients. BMD, T-scores, Z-scores, and bone turnover markers were measured at baseline. FRAX® scores were calculated and adjusted for glucocorticoid dose. Fracture occurrence was monitored for over 10 years. Five (17.9%) patients experienced major osteoporotic fractures during follow-up. The fracture group had significantly lower baseline BMD and T-scores than the no-fracture group. Baseline FRAX® scores for major osteoporotic fracture risk were significantly higher in the fracture group (median 19.0% vs. 5.7%, p = 0.001). The fracture group progressed from osteopenia at baseline to osteoporosis by the end of this study. This study highlights the importance of early and regular bone health assessments in MG patients, particularly those receiving long-term glucocorticoid therapy. The FRAX® tool may be valuable for fracture risk stratification in this population. These findings can inform clinical practice and improve long-term management strategies for MG patients who are at risk of osteoporotic fractures.

Association between antibiotics use and osteoporotic fracture risk: a nationally representative retrospective cohort study.

This population-based retrospective cohort study aimed to estimate the association between antibiotic exposure and osteoporotic fracture risk. Long-term antibiotic use was associated with the risk of osteoporotic fracture. An increase in the number of antibiotic classes prescribed may also be associated with an increased osteoporotic fracture risk. PURPOSE: This study aims to examine the association between antibiotic usage and osteoporotic fractures in a large cohort of Korean adults, with a specific focus on the duration of antibiotic exposure and the number of antibiotic classes used. METHODS: This retrospective cohort study from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from January 1, 2002, to December 31, 2019, included 167,370 Korean adults aged 50 years or older (mean [SD] age, 59.3 [7.82] years; 65,425 [39.09%] women). The cumulative antibiotic prescription days and the classes of antibiotics prescribed between 2004 and 2008 were exposure variables, respectively. The main outcome was a newly diagnosed osteoporotic fracture during follow-up. Cox proportional hazard regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident osteoporotic fractures associated with antibiotic exposure. RESULTS: The antibiotic user group with 91 days had a higher risk of osteoporotic fracture in comparison to the antibiotic non-user group (aHR, 1.12; 95% CI, 1.03-1.21). Additionally, those who used more than four different antibiotic classes had an elevated risk of osteoporotic fracture compared to the non-user group (aHR, 1.10; 95% CI, 1.02-1.18). CONCLUSION: This extensive population-based cohort study conducted on a large population has identified an association between the utilization of antibiotics and an elevated risk of osteoporotic fractures. The cumulative days exposed to antibiotics and osteoporotic fractures may be positively associated.

Early Hip Fracture Surgery in Patients Taking Direct Oral Anticoagulants Improves Outcome.

Background/Objectives: The increasing numbers of already endemic hip fractures in the elderly taking anticoagulants is a growing concern for daily surgical practice. Ample evidence demonstrates decreased morbidity and mortality in the general population when surgery is performed at the earliest possibility. Direct anticoagulants are relatively new drugs that can cause increased perioperative bleeding. Current guidelines propose stopping the drug to allow for elimination before performing elective surgery. Optimal management in urgent hip surgery is presently based on expert opinion with arbitrary cut-offs. In this study, we investigated whether patients taking direct anticoagulants would benefit from early surgical treatment, regardless of the timing since last intake. Methods: A total of 340 patients were included in the analysis, of which 59 took direct anticoagulants. The primary outcomes were time to surgery, postoperative transfusion rate, postoperative hemoglobin decrease, length of postoperative in-hospital stay (LOPS), revision rate, and complication rate (medical and surgical). Results: Our findings showed that the anticoagulated group was fit for discharge earlier when operated on within 24 h (p = 0.0167). Postoperative transfusion and medical complication rate tended to be lower when the operation was performed earlier. Revision rate due to hematomas were higher in the direct anticoagulant group without a relationship to time to surgery. Simple linear regression could not determine a relationship between postoperative hemoglobin change and time to surgery. Conclusions: We suggest that directly anticoagulated patients needing hip fracture surgery must be considered for early surgery.

Treatment effects, adverse outcomes and cardiovascular safety of romosozumab - Existing worldwide data: A systematic review and meta-analysis.

Background: Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials. Methods: A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was "(romosozumab) AND (osteoporosis OR safety)". Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale. Results: 20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51-12.57; p < 0.00001)), total hip (4.04 (95 % CI = 3.10-4.99; p < 0.00001)) and femoral neck bone mineral density (3.77 (95 % CI = 2.90-4.64; p < 0.00001)) at 12 months. There was significantly less likelihood of new vertebral fractures with romosozumab compared to control (odds ratio (OR) 0.42 (95 % CI = 0.20-0.89); p = 0.02) at 12 months of treatment. There was significantly less likelihood of new vertebral fracture at 24 months with 12 months of romosozumab followed by sequential treatment with anti-resorptive compared to control with only anti-resorptive agent use (OR 0.36 (95 % CI = 0.18-0.71); p = 0.003). There was no significant difference in serious adverse events and fatal adverse events with use of romosozumab compared with control in our meta-analyses. There were no significant differences in serious cardiovascular events in Asian population of romosozumab with control group with 12 months of romosozumab treatment followed by 24 months of anti-resorptive agent with OR 1.09 (95 % CI = 0.40-2.96; P = 0.86). There was no significant difference between romosozumab group and control group for the median time to radiographic healing. Our qualitative analysis on Quantitative Computed Tomography (QCT), Finite element analysis (FEA) and bone biopsy analyses demonstrated that romosozumab improved parameters and measures in these domains as well. Conclusion: In conclusion, our study showed that romosozumab was an effective agent to treat osteoporosis with high quality evidence. There were no significant differences in the adverse events, serious adverse events, fatal adverse events identified. Further subgroup analysis of cardiovascular events and cardiovascular death in the total population showed no differences either. The translational potential of this article: Given the results, romosozumab is an effective agent to treat patients with very-high risk of osteoporotic fractures.

Magnetic resonance imaging phantom-based S1 vertebral scores are indicators of fat-water-like osteoporotic changes in postmenopausal women: a pilot study.

STUDY DESIGN: A prospective study. PURPOSE: To assess fat-water-like tissue changes on the 1st sacral vertebra using novel magnetic resonance imaging (MRI) phantombased F- and W-scores and evaluate their diagnostic performances in osteoporosis detection. OVERVIEW OF LITERATURE: Using an uncommonly advanced MRI technique, previous studies have found that fat-water changes were consistent with osteoporosis. The role of routine MRI sequences can be extended in this regard. The S1 vertebra is considered a crucial anatomical site in spine surgeries because it seldom suffers from fractures. Thus, S1 could indicate osteoporotic fat-water changes. METHODS: Forty-two female volunteers (aged 62.3±6.3 years) underwent spine examination with both MRI (including a phantom) and dual-energy X-ray absorptiometry (DXA) following ethical approval. MRI phantom-based F- and W-scoreS1 were defined by normalizing S1 vertebral signal intensities (SIs) by coconut oil and water SIs of the phantom on T1- and T2-weighted imaging, respectively. Using receiver operating characteristic analysis, the diagnostic performances of the new scores for evaluating osteoporosis and vertebral fractures were investigated against standard areal bone mineral density measured with DXA (DXA-aBMD). RESULTS: The F-scoreS1 and W-scoreS1 were greater (4.11 and 2.43, respectively) in patients with osteoporosis than those without osteoporosis (3.25 and 1.92, respectively) and achieved areas under the curve (AUCs) of 0.82 and 0.76 (p<0.05), respectively, for osteoporosis detection. Similarly, the mean F-scoreS1 and W-scoreS1 were higher (4.11 and 2.63, respectively) in patients with vertebral fractures than in those without fractures (3.30 and 1.82, respectively) and had greater AUCs (0.90 for W-scoreS1 and 0.74 for F-scoreS1) than DXA-aBMD (AUC, 0.26; p<0.03). In addition, the F- and W-scoreS1 demonstrated a strong correlation (r=0.65, p<0.001). CONCLUSIONS: The new S1 vertebral-based MRI scores were developed to detect osteoporotic changes and demonstrated improvements over DXA-aBMD in differentiating patients with vertebral fractures.

Analysis of risk factors and predictive efficacy of senile osteoporosis fracture based on biochemical indicators of bone metabolism.

A total of 254 elderly OS patients diagnosed and treated in our hospital during May 2019 to April 2022 was randomly picked, of which 100 patients were finally enrolled. Patients were divided into OS fracture group and non-fracture group according to whether they had OS fracture. The contents of bone mineral density (BMD) and bone metabolism biochemical indexes, including Dickkopf1 (DKK-1), sclerostin (SOST), osteoprotegerin (OPG), osteopontin (OPN), osteocalcin (BGP) and 25 hydroxyvitamin D (25 (OH) D) were detected in lumbar L2c4 and left femoral greater trochanter. The correlation between bone metabolism and BMD was evaluated using Pearson analysis. The risk factors of OS fracture were analyzed using Multivariate logistic regression analysis. The predictive value of biochemical indexes of bone metabolism on the risk of OS fracture was analyzed using ROC curve.

Effects of different drugs in combination with PKP/PVP on postoperative pain in patients with osteoporotic compression fractures: a network meta-analysis.

Objective: This study was designed to evaluate the postoperative pain effect and clinical efficacy of different drugs combined with PKP or PVP in treating osteoporotic vertebral compression fractures (OVCFs) through a systematic review and network meta-analysis. Methods: We searched five electronic databases, namely, MEDLINE (PubMed), EMBASE, Web of Science, Google Scholar, and the Cochrane Central Register of Controlled Trials online, for the treatment of OVCFs through March 2023 with keywords zoledronic acid (ZOL), teriparatide (TPTD or PTH 1-34), and calcitonin (CT) combined with PKP/PVP. The visual analog scale (VAS) and Oswestry Disability Index (ODI) were the primary outcomes of the network meta-analysis, and the secondary outcome was the diagnostic marker bone mineral density (BMD). Results: Eighteen studies involving 2,374 patients were included in this study. The network meta-analysis revealed that, in terms of reducing VAS scores, compared with PVP surgery alone, PVP combined with TPTD was most likely to be the treatment associated with the greatest pain relief [MD = -4.99, 95% CI = (-7.45, -2.52)]. In terms of reducing the ODI dysfunction score, compared with PKP combined with Cal, PKP combined with ZOL had the highest probability of being the best treatment option [MD = -9.11, 95% CI = (-14.27, -3.95)]. In terms of protecting against bone density loss, compared with PKP surgery alone, treatment with PKP combined with ZOL had the best effect [MD = 0.39, 95% CI = (0.13,0.65)]. Conclusions: Based on the network meta-analysis and SUCRA rankings, this study concluded that adding teriparatide has the advantage of reducing VAS pain scores compared with PVP alone and that adding zoledronate is a more effective treatment for reducing ODI scores compared with PKP combined with Cal and preserving BMD compared with PKP alone. However, additional high-quality studies are needed to verify our findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=358445, identifier CRD42022358445.

Non-osteoporotic fractures are associated with increased risk of subsequent major osteoporotic fractures.

We studied the association between non-osteoporotic fractures and future major osteoporotic fractures, using UK health records. Non-osteoporotic fractures were found to increase the risk of major osteoporotic fractures, although to a lesser extent than osteoporotic fractures. This highlights the importance of considering all previous fractures in assessing future fracture risk. PURPOSE: Previous studies demonstrated that osteoporotic fractures-minor and major-increase the risk for future major osteoporotic fractures; we test whether non-osteoporotic fractures are also associated with such increased risk. METHODS: The study is a retrospective cohort study using UK primary care electronic health records. Exposure groups were defined according to fracture location prior to the year 2011 (index date): major, minor, and non-osteoporotic. The outcome of incident major osteoporotic fractures following the index date was compared between the exposure groups and the general population. RESULTS: The general study population included 1,951,388 patients. The exposure groups included 39,931 patients with a prior major osteoporotic fracture, 19,397 with a prior minor osteoporotic fracture, and 50,115 patients with a prior non-osteoporotic fracture. The standardized Incidence Rate Ratio for future major osteoporotic fractures was 2.73 (95% confidence interval: 2.64-2.82), 2.43 (2.32-2.54), and 1.83 (1.74-1.92), respectively. CONCLUSION: Non-osteoporotic fractures are significantly associated with increased risk for future major osteoporotic fractures relative to the general population, yet to a lesser extent compared to major and minor osteoporotic fractures.

Fracture liaison service-a multidisciplinary approach to osteoporosis management.

A fracture liaison service is a systems-level multidisciplinary approach designed to reduce subsequent fracture risk in patients who recently sustained fragility fractures. It is estimated that one in three women and one in five men over the age of 50 years old have osteoporosis. Nonetheless, only 9 to 20% of patients who sustain an initial fragility fracture eventually receive any osteoporosis treatment. With the aim of preventing subsequent fractures, a fracture liaison service (FLS) works through identifying patients presenting with fragility fractures to the hospital and providing them with easier access to osteoporosis care through referrals for bone health and fracture risk assessment and recommendation or initiation of osteoporosis treatment. Currently, there are four major types of FLS models ranging from services that only identify at-risk patients and inform and educate the patient but take no further part in communicating their findings to other stakeholders in patients' care, to services that identify, investigate, and initiate treatment at the other end of the spectrum. In this article, we review the benefits, challenges, and outcomes of FLS in the American healthcare system with further exploration of the roles each member of the multidisciplinary team can play in improving patients' bone health.

Drug utilization pattern of romosozumab and other osteoporosis treatments in Japan, 2019-2021.

INTRODUCTION: Describe real-world treatment of osteoporosis and romosozumab treatment patterns in Japan. MATERIALS AND METHODS: Data for patients initiating romosozumab or other antiosteoporotic medications between March 01, 2018, and May 31, 2022, were extracted from the Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. Patients were categorized into four cohorts: those who newly initiated romosozumab within the first (MDV: n = 4782; JMDC: n = 2578) or second (MDV: n = 3888; JMDC: n = 2446) year after launch and those who initiated teriparatide (TPTD; MDV: n = 14,576; JMDC: n = 8259) or non-TPTD antiosteoporotic medications within the first year of romosozumab launch (MDV: n = 352,142; JMDC: n = 185,785). RESULTS: Mean age, sex, baseline cardiovascular history, comorbidities, and concomitant medications were similar across cohorts. In the MDV database, fracture history was higher in the romosozumab year-1 (59.3%), year-2 (64.1%), and TPTD (65.5%) cohorts versus the non-TPTD cohort (24.4%). Similar rates were identified in the JMDC database: romosozumab year-1 (64.7%), year-2 (66.6%), TPTD (67.5%), and non-TPTD (27.8%). Vertebral fractures were most common in all cohorts. 12-month romosozumab discontinuation varied between the year-1 and year-2 cohorts in MDV (62.4% and 58.8%) and JMDC (57.1% and 52.7%), whereas mean number of injections remained consistent (MDV: 9.7 and 9.8; JMDC: 7.3 and 7.8). Romosozumab persistence was lower in year-1 versus year-2 (MDV: 37.6% and 42.9%; JMDC: 41.2% and 47.3%). CONCLUSION: Patients initiating romosozumab and TPTD had a high fracture history. Given the dual effects of promoting bone formation and suppressing resorption, improving romosozumab adherence and persistence over time may be important for antiosteoporotic therapy.

Association of muscle health impairment and atherosclerosis with major osteoporotic fracture risk in Taiwanese Vegetarians.

Objectives: Despite the beneficial effects of "vegetarian style" diet on atherosclerosis, it is also proven potentially detrimental to bone health. The influence of muscle health or atherosclerosis on major osteoporotic fracture (MOF) risk in vegetarians has rarely been explored. This prospective study aimed to investigate an association of MOF risk with muscle health and atherosclerosis in vegetarians. Materials and Methods: We conducted a questionnaire survey with the Mini-Nutritional Assessment (MNA) on 39 vegetarians. The 10-year probability of MOF was determined using the Taiwanese Fracture Risk Assessment (FRAX®) calculator. Appendicular skeletal muscle (ASM) mass and bone mineral density were measured with dual-energy X-ray absorptiometry. Physical performance was evaluated using the 6-min walk test (6MWT). Common carotid artery intima-media thickness (ccIMT) was determined using sonography. Serum levels of parathyroid hormone (PTH), Vitamin D, adiponectin, and leptin were measured. Results: Eleven (28.2%) of 39 vegetarians had a moderate-high risk of MOF, defined by FRAX-calculated risk ≥10%. These subjects had lower ASM (P < 0.005) and 6MWT distances (P < 0.01) but greater ccIMT than those with low risk. The MOF risk was negatively correlated with ASM (r = -0.51, P < 0.001) and 6MWT distances (r = -0.62, P < 0.001) but positively correlated with ccIMT (r = 0.56, P < 0.001). Linear regression analysis revealed that MOF risk scores were negatively associated with ASM and 6MWT distance while positively associated with ccIMT. There was no significant association of MOF risk with MNA scores, serum levels of PTH, Vitamin D, adiponectin, or leptin. Conclusion: Decreased ASM mass, reduced physical performance, and atherosclerosis are significantly associated with MOF risk in vegetarians.

Global current research status and future hotspots in osteoporotic fracture based on bibliometric assessment and visualization techniques.

BACKGROUND: In the past decade, the evolution of themes in the field of osteoporotic fractures has changed from epidemiology and prediction of long-term morbidity, risk assessment of osteoporotic fractures, and zoledronic acid and denosumab in the treatment of osteoporosis to treatment guidelines for osteoporosis and the side effects caused by anti-osteoporotic drugs. AIM: To understand the trends and hotspots in osteoporotic fracture research. METHODS: Original articles were retrieved between January 1, 2010, and December 31, 2019, from the Web of Science Core Collection database. CiteSpace software facilitated the analysis and visualization of scientific productivity and emerging trends. RESULTS: Nine studies were identified using bibliometric indices, including citation, centrality, and sigma value, which might indicate a growing trend. Through clustering, we identified six major hot subtopics. Using burst analysis, top-5 references with the strongest bursting strength after 2017 were identified, indicating a future hotspot in this field. CONCLUSION: Current hot subtopics in osteoporotic fracture research include atypical femoral fractures, androgen deprivation therapy, denosumab discontinuation, hip fractures, trabecular bone score (TBS), and bone phenotype. Management and prevention of secondary fractures in patients with osteoporotic fractures, TBSs, and long-term administration strategy for zoledronic acid are expected to become research hotspots.

The relation of osteoporotic vertebral fractures and spine degeneration on the occurrence of complications: a systematic review.

STUDY DESIGN: Systematic review. PURPOSE: Osteoporotic vertebral fractures (OVFs) and degenerative spine conditions are age-related and associated with higher morbidity and mortality and greater health care costs. The relationship between OVFs and prevalent spine degeneration is rarely reported. The aim of this study was to systematically review current literature on the influence of preexisting degenerative spine conditions in patients with OVFs on the occurrence of complications during and after treatment. METHODS: A systematic literature review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed using Web of Science and MEDLINE. We considered English and German articles published from January 1990 to December 2022. The inclusion criteria were patients with OVFs and preexisting spinal degeneration with complications such as subsequent fractures, deformity, implant failure and surgical and general complications. The included studies were controlled trials, cohort studies, and case series. RESULTS: Ten articles met the inclusion criteria (two prospective studies, seven retrospective studies and one case series). These were divided into two groups: studies on OVFs in patients with coexisting degenerative spine conditions (n = 5) and studies on OVFs following surgical treatment for degenerative spine conditions (n = 5). Three studies reported more complications in patients with OVFs and severe degeneration. One study stated the opposite. One study did not find any correlation. The remaining studies described complications narratively. Subsequent fractures were the most frequent complications. CONCLUSION: OVFs in patients with preexisting spinal degeneration seem to cause more complications. In addition to subsequent fractures, other complications have rarely been examined. The presence of degenerative changes or undergoing surgical correction may increase the risk of subsequent fractures.

Oral dehydroepiandrosterone supplementation enhances osteoporotic fracture healing in the OVX rats.

Osteoporosis easily causes delayed fracture union, even non-union. It has been demonstrated that dehydroepiandrosterone (DHEA) supplementation can increase estrogen levels and improve bone mineral density (BMD) in the elderly, while the role of DHEA on fracture healing remains unknown. This study aimed to elucidate the impact of DHEA supplementation on osteoporotic fracture healing. Seventy-two female Sprague-Dawley rats were used. Forty-eight rats received ovariectomy (OVX), and the remaining rats received a sham OVX operation (sham group). A right transverse femoral osteotomy was performed in all rats at 12 weeks post-OVX. OVX rats were randomly allocated into 2 groups (n = 24 in each group): (i) ovariectomized rats (control group) and (ii) ovariectomized rats treated with DHEA (DHEA group, 5 mg/kg/day). The DHEA supplementation was initiated on the first day post-fracture for 3, 6, and 12 weeks. Fracture healing was evaluated by radiography, histology, biomechanical analysis, and dual-energy X-ray absorptiometry (DEXA). Serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA). At 3 and 6 weeks, radiographs revealed reduced calluses formation and lower radiographic scores in the control group than in other groups. The sham and DHEA groups showed higher BMD and bone mineral content (BMC) at the fracture site than the control group after fracture. Histological analysis revealed the fracture callus was remodeled better in the sham and DHEA groups than in the control group. At the early phase of healing, DHEA supplementation increased osteoblast number, callus area, and cartilage area than the control group. An increased bone area was observed in the DHEA group than in the control group at the late phase of healing. Additionally, improved biomechanical characteristics were observed in both the sham and DHEA groups than those in the control group post-fracture. ELISA showed higher levels of insulin-like growth factor-1 (IGF-1) and 17ß-estradiol (E2) in the DHEA group than in the control group post-fracture. Furthermore, the DHEA group exhibited significantly elevated alkaline phosphatase (ALP) and osteocalcin (OC) levels compared to the control group at 6 and 12 weeks. The DHEA group and the control group did not exhibit a notable difference in TRAP-5b levels. The present study demonstrated that the DHEA treatment has a favorable impact on osteoporotic fracture healing by enhancing callus formation, consolidation, and strength in the OVX rats.