Fracture Risk Research Articles

Biases in the performance of FRAX without BMD in predicting fracture risk in a multiethnic population with diabetes: the Diabetes & Aging Study.

Fracture risk calculators, such as the Fracture Risk Assessment Tool (FRAX), calculate the risk of major osteoporotic (MOF) and hip fracture, but do not account for the excess risk of fracture in people with diabetes. We examined the predictive performance of FRAX without BMD in ethnically diverse, older patients with diabetes. Patients included were between ages 65-89 from the Kaiser Permanente Northern California Diabetes Registry and not already taking osteoporosis medications. Race and ethnicity were self-identified. We calculated FRAX without BMD based on baseline characteristics and assessed how well FRAX predicted MOF and hip fracture over follow-up. Predictive performance was based on measures of discrimination (area under the receiver operator curve, AUC) and calibration (observed-to-predicted ratio, O/P). We identified 96 914 patients (47.0% female), of whom 5383 (5.6%) and 1767 (1.8%) had MOF and hip fracture, respectively, over a mean follow-up of 4.3years. The AUC for MOF and hip fracture were 0.72 and 0.77, respectively. FRAX mildly underestimated MOF and hip fracture rates (O/P 1.2 for both) overall. Discrimination was similar by race and ethnicity and diabetes duration but was worse in those over age 75 (AUC < 0.7). In some groups, there were substantial calibration errors, such as Hispanic women (O/P: 1.8 and 1.5), Black men (O/P: 1.5 and 1.8), those with duration of diabetes ≥20years (O/P: 1.6 and 1.5), and those over the age of 80 (O/P: 1.4 and 1.2) for MOF and hip fracture, respectively. While the discriminatory performance of FRAX without BMD was good overall in patients with diabetes, it underestimated risk in Hispanic women, Black men, those with long duration of diabetes, and in the oldest patients with diabetes. These algorithmic biases suggest that diabetes-specific tools may be needed to stratify fracture risk in patients with diabetes.

Cardiovascular disease, bone fracture, and all-cause mortality risks among postmenopausal women by arthritis and veteran status: A multistate Markov transition analysis.

Arthritis, a chronic inflammatory condition linked to cardiovascular disease (CVD) and bone fracture, is more frequent among military veterans and postmenopausal women. This study examined correlates of arthritis and relationships of arthritis with risks of developing CVD, bone fractures, and mortality among postmenopausal veteran and non-veteran women. We analyzed longitudinal data on 135,790 (3,436 veteran and 132,354 non-veteran) postmenopausal women from the Women's Health Initiative who were followed-up for an average of 16years between enrollment (1993-1998) and February 17, 2024. Regression and multistate Markov modeling were applied to meet study objectives. The prevalence of arthritis at enrollment (1993-1998) did not differ by veteran status in a fully adjusted logistic model. Variable selection yielded 5 key predictors of prevalent arthritis among veterans and 15 key predictors among non-veterans. In fully-adjusted Cox models, prevalent arthritis was associated with CVD (hazard ratio [HR] = 1.08, 95% confidence interval [CI]: 1.05, 1.10) and all-cause mortality (HR = 1.03, 95% CI: 1.01, 1.05) risks among non-veterans only, but was not associated with bone fracture risk irrespective of veteran status. Transition probabilities between health and CVD and between bone fracture and death were higher among women with vs. without arthritis. The latter transition was more strongly related to arthritis among non-veteran vs. veteran women. In conclusion, among postmenopausal women, prevalent arthritis was associated with greater probabilities of transitioning from a healthy state to CVD and from bone fracture to death, with worse prognosis after bone fracture among those who did not serve in the military.

Hearing loss and risk of major osteoporotic fracture: a population-based cohort study in the United Kingdom

SummaryUsing the UK Clinical Practice Research Datalink, our cohort study matched 237,297 individuals with hearing loss (HL) to 829,431 without HL. The study found an 8–10% higher risk of major osteoporotic fracture in individuals with HL compared to those without. Additionally, within the HL cohort, we identified risk factors for potential inclusion in fracture risk models.PurposeAssess association between hearing loss (HL) and major osteoporotic fracture (MOF; spine, wrist/forearm, shoulder/proximal humerus, hip) in individuals aged ≥ 60 years, and risk factors for MOF in individuals with HL.MethodsFrom the UK Clinical Practice Research Datalink, our cohort study matched individuals aged ≥ 60 years diagnosed with HL (READ/ICD-10 codes; 01January2001–31December2021; index event), without secondary osteoporosis causes, with up to five individuals without HL (birth, index year, sex, general practice). Incidence rates and Cox proportional hazard ratios (HL vs. no HL; stratified by low/high fracture risk) were calculated for MOF and hip fracture; multivariate logistic regression assessed risk factors for MOF and hip fracture (HL cohort).ResultsA total of 237,297 individuals with HL matched to 829,431 without HL, with a median age of 74 and 72 years, respectively. Compared with those without HL, individuals with HL had greater frailty (severe electronic frailty index, 5.9% vs. 2.7%), higher incidence of prior falls (14.1% vs. 10.6%), longer mean follow-up with higher incidence of MOF and hip fractures (5.1 vs. 4.4 years, 20.1 and 5.32 vs. 16.58 and 4.54 per 1000 person-years, respectively) and higher risk of MOF and hip fracture (adjusted HR, 1.10 and 1.08, respectively). Significant risk factors for MOF and hip fracture included age ≥ 70 years, fracture history, falls, osteoporosis diagnosis, chronic obstructive pulmonary disorder and cardiovascular disease (HL cohort).ConclusionIn individuals with HL, we observed an 8–10% higher risk of MOF and hip fracture versus individuals without HL and identified risk factors for potential inclusion in fracture risk models.

Biomechanical analysis of a newly designed and 3D printed plate-locking interbody cage: an observational study of finite element analysis

Anterior cervical interbody fusion (ACDF) has become a classic surgical procedure for the treatment of cervical degenerative diseases, and various interbody cages are widely used in this procedure. We used 3D printing technology to produce a new type of plate-locking cage, anticipating to achieve high fusion rate with the high biomechanical stability. This study is to compare the biomechanical characteristics between a newly designed interbody cage and a conventional Zero-profile cage during ACDF using finite element analysis. The CT images of a 35-year-old healthy male were extracted and saved in DICOM format. Mimics Research 19.0, Geomagic Wrap 2017, NX12. 0, Abaqus 6.14 were used to construct the finite element models, then, titanium plate, titanium screw, cages, and the residual parts of both groups were assembled with reference to the surgical approach of ACDF (C4/5), following the successful establishment of both surgical models, a total of six boundary and loading conditions were tested, including flexion, extension, left and right bending, and left and right axial torsion. It is found that the plate stress peak of the new cage group decreased 73.78 MPa, 70.00%; 77.17 MPa, 70.67%; 59.77 MPa, 64.97%; 49.94 MPa, 58.28%; 44.55 MPa, 68.38%; 46.14 MPa, 68.00% in flexion, extension, left bending, right bending, left axial torsion and right axial torsion, respectively. There were no obvious increases of C5 upper endoplate stress peak between these two surgical models (< 50%), except 11.68 MPa, 153.08%; 6.55 MPa, 51.45%; in flexion and extension. The 3D-printed porous plate-locking cage was shown to be biomechanically stable compared to the conventional Zero-profile cage, and it is worth noticing that the stress on the plate of the new cage is less than that on screw of the conventional cage, which indicates that the risk of fracture, loosening, and prolapse of the new cage is less likely to occur.

Metaphyseal comminution in distal radius fractures: a predictor of secondary fragility fractures and the role of osteoporosis treatment.

Distal radius fractures (DRFs) are common in patients with osteoporosis and associated with increased risks for subsequent fractures. Metaphyseal comminution in patients with DRFs may indicate severe osteoporosis and heightened bone fragility. However, its relationship with the risk of secondary fragility fractures remains unclear. This study aimed to evaluate the incidence of secondary fractures in patients with DRFs involving metaphyseal comminution and assess the effectiveness of osteoporosis treatment in reducing this risk. In this retrospective cohort study, 134 patients aged ≥ 50years underwent DRF surgery at a single institution from July 2018 to December 2022. The patients were allocated into groups by the presence (n = 45) or absence (n = 89) of metaphyseal comminution. The primary outcome was secondary fracture incidence. A multivariate Cox model was used, adjusting for age, sex, body mass index, bone mineral density, osteoporosis treatment type, and dementia. Secondary fractures were significantly more frequent in the comminution group (17.8%) than in the non-comminution group (3.4%) (p = 0.004). Metaphyseal comminution was associated with 5.2-fold increased secondary fracture risk (hazards ratio: 5.2, 95% confidence interval: 1.4-10.7, p = 0.004). The patients administered combination therapy (active vitamin D plus bisphosphonates or anabolic agents) had notably lower secondary fracture rate than did those receiving vitamin D alone (5.6% vs. 15.4%, p = 0.046). Metaphyseal comminution in patient with DRFs significantly elevated secondary fracture risk; combination osteoporosis therapy might mitigate this risk. These findings underscore the need for robust osteoporosis management in high-risk patients, suggesting metaphyseal comminution should be crucial for fracture risk stratification.

Addressing healthcare disparities and improving osteoporosis management in rural communities: a cluster randomized control trial.

Rural communities face limited healthcare access, financial constraints, and transportation barriers leading to health disparities. This study examined interventions that reduced health disparities in increasing the outpatient attendance and treatment rate of anti-osteoporosis medication (AOM), while identifying factors contributing to therapy refusal in rural communities. A total of 567 patients were randomized at the community level into three groups: multicomponent integrated care (MIC), osteoporosis care only (OC), and usual care (UC). Fracture Risk Assessment Tool and dual-energy X-ray absorptiometry scans were used to evaluate the osteoporosis and osteoporotic fracture risk. High- and moderate-risk patients were advised to pursue further hospital-based assessments and treatment. Both the MIC and OC groups received five interventions to address rural barriers, including specialist access, disease education, overcoming transportation barriers, peer support, and dedicated case managers. However, UC excluded transportation assistance, peer support, and case management. Outcomes measured included outpatient attendance, AOM treatment rates, and factors affecting hospital assessment refusal, analyzed via multivariable logistic modeling. In the MIC group, 73.3% of patients attended the outpatient clinic and 58.6% received AOM. In the OC group, 81% patients attended and 69.3% received AOM. Conversely, in the UC group, only 4.1% attended and received AOM. Significant differences in attendance and AOM rates were found between the MIC and UC groups and between the OC and UC groups (p < .001 for both). Common barriers included beliefs that treatment was unnecessary and lack of hospital access. Risk factors hindering outpatient attendance include male sex, low education, low budget, multiple disabilities, and osteopenia diagnosis. Addressing transportation barriers and implementing dedicated case management are crucial for improving healthcare access among rural patients. ClinicalTrials.gov NCT05104034.

Ultra-processed food intake and prevalence of osteoporosis in US adults aged 50years and older: a cross-sectional analysis.

Using regression analysis and adjusting for covariates, 24-h recall data from adults 50years and over in four cycles of NHANES were examined for associations between prevalence of osteoporosis and intakes of UPF as a proportion of daily energy intake. Mean (SE) intake of UPF as a proportion of total daily energy ranged from 29.5% (0.3) in the lowest quintile to 76.3% (0.3) in the highest. 50.5% of womenand 28.0% of men had osteopenia, 8.2% and 1.8%, respectively, had osteoporosis. Increased risk of osteopenia or osteoporosis was observed in the highest quintile of UPF intake compared to that of the lowest: OR 1.52 (95% CI 1.28, 1.79). The odds of self-reported prior fractures at hip, wrist, or spine in women increased by 1.9% for every percentage increase in proportion of UPF intake (95% CI 1.003, 1.035). Increased risk of fracture was not observed among men. These findings indicate an association between osteoporosis and osteopenia and the intake of UPF as a proportion of total daily energy. Further investigation into the impact of dietary quality on osteoporosis and fracture risk is warranted, particularly in post-menopausal women.

The Risk of Postoperative Periprosthetic Femoral Fracture After Total Hip Arthroplasty Depends More on Stem Design Than Cement Use: An Analysis of National Health Data from England.

In this study, we estimated the risk of surgically treated postoperative periprosthetic femoral fractures (POPFFs) associated with femoral implants frequently used for total hip arthroplasty (THA). In this cohort study of patients who underwent primary THA in England between January 1, 2004, and December 31, 2020, POPFFs were identified from prospectively collected revision records and national hospital records. POPFF incidence rates, adjusting for potential confounders, were estimated for common stems. Subgroup analyses were performed for patients >70 years of age, with non-osteoarthritic indications, and with femoral neck fracture. POPFFs occurred in 0.6% (5,100) of 809,832 cases during a median follow-up of 6.5 years (interquartile range [IQR], 3.9 to 9.6 years). After cemented stem implantation, the majority of POPFFs were treated with fixation. Adjusted prosthesis time incidence rates (PTIRs) for POPFFs varied by stem design, regardless of cement fixation. Cemented composite beam (CB) stems demonstrated the lowest risk of POPFF. Collared cementless stems had an equivalent or lower rate of POPFF compared with the current gold standard of a polished taper slip cemented stem. Cemented CB stems were associated with the lowest POPFF risk, and some cementless stem designs outperformed modern cemented stem designs. Stem design was strongly associated with POPFF risk, regardless of the presence of cement. Surgeons, policymakers, and patients should consider these findings when considering femoral implants in those most at risk for POPFF. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Correlation Analysis Between the Geriatric Nutritional Risk Index Hip Fracture in Male: Based on the National Health and Nutrition Examination Survey Database.

Hip fractures (HFs) are common in elderly patients and are associated with high mortality rates and functional impairment. Malnutrition has been shown to negatively impact postoperative survival rates in HF patients. However, the relationship between the Geriatric Nutrition Risk Index (GNRI) and the risk of HF remains unclear. This study aims to evaluate the association between GNRI and HF risk, with a particular focus on the elderly male population.We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) for the periods 2007-2010, 2013-2014, and 2017-2018. Through multivariate regression analysis, we assessed the association between GNRI and HF and performed stratified and subgroup analyses to further explore this relationship. Additionally, we utilized restricted cubic splines (RCSs) to investigate the potential nonlinear relationship between GNRI and HF risk.The study found that gender significantly influenced the relationship between GNRI and HF (p for interaction =0.002). In males, GNRI was significantly negatively associated with the risk of HF (OR <1, p<0.05). RCS analysis showed that the relationship between GNRI and HF risk in elderly males might be linearly negative. The critical threshold for GNRI was identified as 104.14, beyond which the risk of HF significantly decreased.This study demonstrates a linear negative correlation between GNRI and the risk of HF in elderly males, with a GNRI of 104.14 identified as the critical threshold for predicting the risk of hip fractures.

Drilling and Groove-cutting Technique for Safe and Complete Removal of Forehead Osteomas on the Anterior Table of the Frontal Sinus.

Forehead osteomas are benign tumors commonly excised for cosmetic and functional reasons. However, removing osteomas from the anterior table of the frontal sinus presents specific challenges, particularly in determining the appropriate removal thickness. Inaccurate resection depth may result in fracture or perforation of the anterior table of the frontal sinus, or incomplete resection. The authors propose a novel drilling and groove-cutting technique to ensure safe and complete excision while minimizing risks of fracture or perforation of the anterior table. In this study, the authors present a 51-year-old female patient with a recurrent osteoma. Preoperative computed tomography (CT) imaging-guided depth-limiting drilling at the osteoma's center, followed by groove-cutting to establish excision boundaries. Then divided osteoma blocks were excised completely. Postoperatively, the patient showed no sensory deficits or forehead asymmetry and achieved pleasing frontal contour with minimal scarring. This technique effectively safeguards the anterior table and ensures complete removal, demonstrating its utility in craniofacial surgery.

Effects of femoral neck width and hip Axis length on incident hip fracture risk: a registry-based cohort study.

Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) is widely used in clinical practice to assess fracture risk and guide management. DXA can also assess hip geometry, including femoral neck width (FNW) and hip axis length (HAL), which have both been associated with increased risk for hip fracture independently from BMD. Our objective was to assess if FNW predicts hip fracture independently from other factors including HAL. We performed a retrospective cohort study using the Province of Manitoba BMD registry. The study population comprised 75 095 individuals (90.8% women), mean age 64.7years, with baseline hip BMD and hip geometry parameters. Linked health records were used to ascertain subsequent hospitalization with hip fracture as a primary diagnosis. During a mean follow up of 8.3 (SD 5.1) years, 2341 incident hip fractures were recorded. Each SD increase in age- and sex-adjusted FNW was associated with incident hip fracture (HR 1.15, 95% CI 1.10-1.19) which was unchanged after adjustment for height, weight, femoral neck BMD and clinical risk factors. However, FNW showed a significant positive correlation with HAL (r = 0.68). When further adjusted for HAL, FNW was no longer associated with increased risk for hip fracture (HR 0.98, 95% CI 0.94-1.03). A similar pattern was seen for femoral neck, intertrochanteric and non hip fractures. In contrast, increased risk of hip fracture was consistently seen with each SD increase in HAL even after adjustment for all covariates including FNW (HR 1.35, 95% CI 1.28-1.42). In conclusion, FNW is a risk factor for hip fracture before but not after adjustment for HAL. HAL, on the other hand, robustly and independently predicts hip fracture, including both femoral neck and trochanteric fractures.

Update over de diagnose en behandeling van postmenopauzale osteoporose

Update on the diagnosis and treatment of postmenopausal osteoporosis Osteoporosis is characterized by a low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in spontaneous or low-impact fractures. These fractures are associated with a significant impact on morbidity and mortality. This article provides a literature overview of the most recent guidelines of the Belgian Bone Club with regard to screening, diagnosis, treatment and follow-up of postmenopausal osteoporosis. The Belgian Bone Club recommends screening for osteoporosis in all women ≥ 50 years, or at the age of menopause if this occurs earlier. After a positive screening, the guidelines recommend an evaluation of previous fragility fractures, a measurement of bone mass by DXA and a calculation of the fracture risk with computer-based algorithms. Based on these three criteria, we categorize the fracture risk as low, high or very high. Lifestyle measures and sufficient calcium and vitamin D intake are recommended in all categories. Antiresorptive treatment should be considered for high-risk patients (selective estrogen receptor modulators, bisphosphonates or the anti-RANK antibody denosumab). For patients at very high-risk, anabolic therapy, such as teriparatide or romosozumab, is preferred. All anabolic therapy should be followed by antiresorptive therapy. It is recommended to regularly monitor the effectiveness and tolerance of therapy, including a DXA measurement every 2 to 5 years.

Risk-Weight Calculation of Candidate Risk Factors for Incidental Osteoporotic Fracture in Patients with Rheumatic Diseases: A Potentially Accurate Approach

Background and Objectives: To assess the risk of osteoporotic fractures in patients with rheumatic diseases (RDs), we introduced a new approach for predicting incident osteoporotic fractures (OF), employing a risk-weight calculation for each candidate risk factor. Materials and Methods: RD outpatients were picked up, and their histories, including OFs, were studied. A Cox regression analysis that evaluated candidate risk factors was conducted with a multivariate model. The variants were selected as candidate risk factors that showed statistical significance using a univariate model. Using the risk ratio or the β-value and p-value, different approaches to acquire a total risk weight (TRW) for each patient were determined to compare the sensitivity and specificity among the approach methods. The cut-off index (COI) was determined using receiver operating characteristic analysis. Sensitivity and specificity for incident OFs were determined using the Kaplan–Meier survival analysis. Results: In a total of 1228 patients, incidental OF occurred in 179 (14.58%) who were included. Factors with significantly higher risk ratios were a history of vertebral and non-vertebral fractures (p &lt; 0.001), cognitive impairment (p &lt; 0.001), anti-osteoporosis drug intervention (p &lt; 0.001), and rehabilitation (p &lt; 0.001). The excellent approach to acquire the best sensitivity and specificity was to calculate the β-value multiplied by the logarithm of the p-value based on 0.05, including non-significant factors (sensitivity: 31.2%, specificity: 94.9%, and area under the curve (AUC): 0.774) compared to 29.4%, 91.6%, and 0.723, respectively, with a counted significant risk factors approach. Conclusions: This novel approach, which includes non-significant factors, can achieve a more accurate sensitivity and specificity to accidental OF in patients with RDs.

Improved primary stability and load transfer of a customized osseointegrated transfemoral prosthesis compared to a commercial one

BackgroundTransfemoral osseointegrated prostheses, like other uncemented prostheses experience the risk of aseptic loosening and post-operative periprosthetic fractures, with an incidence between 3% and 30%. To date, however, osseointegrated off-the-shelf prostheses are manufactured in a limited number of sizes, and some patients do not meet the strict eligibility criteria of commercial devices. A customized osseointegrated stem was developed and a pre-clinical in vitro investigation of the stem was performed, to evaluate its biomechanical performance.Materials and methodsSix human cadaveric femurs were implanted with commercial stems, while the six contralateral were implanted with customized stems. Three more femurs that did not meet the eligibility criteria for the commercial stems were implanted with the customized stems. Two different loading scenarios (compression-flexion, and torsion) were simulated to measure the primary implant stability and the load transfer. For both loading scenarios, the displacements of the implant with respect to the host bone, and the strains on the bone surface were measured using digital image correlation (DIC). To measure the pull-out force, a tensile force was applied to the prostheses.ResultsThe translational inducible micromotions during the compression-flexion test of the OsteoCustom stem were more than 4 times smaller than the commercial one (p < 0.05). The rotational inducible micromotions of the OsteoCustom stem were more than 3 times smaller than the commercial one (p < 0.05). Similar results were found from the torsional test. The full-field strain distribution of the commercial stem showed a slightly higher strain concentration near the stem tip (maximum principal strain = 1928±127 µɛ) than the OsteoCustom (maximum principal strain = 1758±130 µɛ). Similar results were found for the femurs that did not meet the eligibility criteria for the commercial stems and could be implanted with the OsteoCustom. No statistically significant difference was found in the extraction force between the two groups.Discussion and conclusionThese results support the hypothesis that the OsteoCustom stem can offer better primary stability and load distribution compared to commercial implants. The outcome highlighted the potential benefits of the OsteoCustom prosthesis, which is capable of including a wider range of femoral anatomies than the current standard.

Does Baseline Hounsfield Unit Predict Patients’ Outcomes Following Surgical Management of Unstable Osteoporotic Thoracolumbar Fractures?

Background and Objectives: Osteoporotic fractures in the thoracic/lumbar spine pose significant challenges in surgical management, with high risks of complications. This study investigates the role of preoperative CT scans and Hounsfield Units (HUs) in predicting postoperative outcomes. Materials and Methods: A retrospective study was conducted from November 2015 to January 2018. Sixty-one patients over 60 years of age with unstable osteoporotic thoracolumbar spine fractures (OF: 3–4) were included. Preoperative CT scans were performed to measure HU values. Postoperative standing X-rays were taken at 3–12 months to assess signs of loosening, adjacent fractures, or screw dislodgement. HU was divided into quartiles: Q1 (&lt;56.24), Q2 (56.24–72.63), Q3 (72.63–87.59), and Q4 (&gt;87.59). Results: Out of the 61 patients, 14 (23%) exhibited signs of screw loosening, adjacent fractures, or screw dislodgement within 3 to 12 months postoperatively. The mean HU value measured was 65.21, with a range from 21.43 to 140.7. Notably, all patients with observed loosening or dislodgement had HU values below 68. HU significantly predicted mortality, with the second quartile showing a markedly increased risk (adjusted odds ratio [aOR] = 8.12; p = 0.044). However, HU quartiles were not significant predictors of other outcomes. Other factors (fracture level and ASA classification) also influenced clinical outcomes, particularly mortality. Conclusions: HU values from preoperative CT scans are crucial in predicting the risk of screw loosening, dislodgement, and adjacent fractures in osteoporotic spinal fractures. Integrating HU assessment into clinical practice can improve preoperative planning, allowing for more targeted surgical interventions and better clinical outcomes.

MiR-208a-3p discriminates osteoporosis, predicts fracture, and regulates osteoclast activation through targeting STC1

BackgroundOsteoporosis (OP) frequently occurs in post-menopausal women, increasing the risk of fracture. Early screening OP could improve the prevention of fractures.This study focused on the significance of miR-208a-3p in diagnosing OP and development regulation, aiming to explore a novel biomarker and therapeutic target for OP.MethodsThe study enrolled a total of 154 post-menopausal women and grouping was performed based on the incidence of OP and fracture. The significance of miR-208a-3p was evaluated from the perspectives of menopausal correlation, OP diagnosis, and fracture prediction. In mechanism, the regulatory effect and mechanism of miR-208a-3p on osteoclast activation was investigated.ResultsmiR-208a-3p was menopause-related showing a negative correlation with E2 and positive correlations with FSH and LH. Significant upregulation of miR-208a-3p was observed in post-menopausal women with OP and showed significant diagnostic potential. Increasing miR-208a-3p was positively correlated with bone metabolism markers and negatively correlated with BMD of post-menopausal women with OP. Moreover, miR-208a-3p was also identified as a risk factor for fracture. STC1 was identified as a direct target of miR-208a-3p and was negatively regulated by miR-208a-3p. Silencing miR-208a-3p significantly alleviated macrophage inflammation and osteoblast activation, which was reversed by the knockdown of STC1.ConclusionSerum miR-208a-3p served as a diagnostic biomarker for OP and a risk factor for fracture in post-menopausal women. miR-208a-3p regulated macrophage inflammation and further mediated osteoclast activation via targeting STC1.

P-20 EARLY ZOLEDRONIC ACID TREATMENT IN A PEDIATRIC CASE OF OSTEOGENESIS IMPERFECTA TYPE V: CLINICAL OUTCOMES AND THE ROLE OF IFITM5 (BRIL) MUTATION

Abstract Introduction Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility, low bone mass, and frequent fractures. OI is typically associated with mutations in the COL1A1 and COL1A2 genes, but a subset of cases, such as OI type V, is linked to mutations in the IFITM5 gene, also known as BRIL (bone-restricted IFITM-like). Clinical Case This report presents a case of a 2-year-old boy diagnosed with OI type V, a rare form of the disease caused by a mutation in BRIL. The patient exhibited multiple recurrent bone fractures beginning in infancy, though there was no family history of bone disease or consanguineous marriage. Physical examination revealed that the patient was of normal weight and height for his age, with neurodevelopmental milestones met. Laboratory tests showed elevated alkaline phosphatase (ALP) levels, indicative of increased bone turnover, while other values were within normal ranges. Radiological evaluations confirmed an active fracture in the left tibia but showed no additional pathological involvement. Genetic testing identified a de novo C&amp;gt;T variant in the IFITM5 gene, confirming the diagnosis of OI type V. The patient was treated with intravenous zoledronic acid (ZA), a bisphosphonate therapy, which is currently being tested in infants and toddlers for OI treatment. The treatment led to a significant reduction in fracture recurrence and a decrease in ALP levels, demonstrating its efficacy in managing the disease. Despite these positive outcomes, certain hallmark features of OI type V, such as hyperplastic callus formation and new periosteal bone growth, were not observed during follow-up, possibly due to the early initiation of ZA therapy. OI type V is distinguished from other forms of OI by hyperplastic callus formation and increased osteoblast activity, often accompanied by elevated ALP levels. Radiographic and histological findings specific to this type include periosteal bone growth and a reticular lamellation pattern in the bone matrix. Although ZA has shown promise in reducing fracture risk and improving clinical outcomes, its long-term efficacy in preventing other disease manifestations, such as intramembranous ossification, remains uncertain. The underlying pathological mechanisms of OI type V, particularly the role of BRIL, are not yet fully understood. Further research into the activation of BRIL in osteoblasts could lead to the development of targeted therapies that address the root cause of the disease. While ZA therapy has been effective in managing the immediate symptoms of OI type V, a deeper understanding of the disease's genetic and molecular basis is crucial for improving long-term treatment outcomes. In conclusion, the IFITM5 (BRIL) mutation is recognized as the genetic cause of OI type V. Early intervention with ZA has shown positive effects in managing the disease, but further research is needed to fully understand the pathological mechanisms and to develop treatments that can address all aspects of the disease.Table 1:Lab workout (age 2)ALP = alkaline phosphatase; AST = aspartate transaminase; BUN = blood urea nitrogen; GGT = gamma-glutamyl transferase; CBC: complete blood count

Efficacy and safety of teriparatide in kidney transplant recipients with osteoporosis and low bone turnover: a real-world experience.

Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD), enhancing survival and quality of life. However, kidney transplant recipients (KTRs) are at high risk for bone disorders, particularly low bone turnover disease, which increases fracture risk. Teriparatide, an anabolic agent, may provide a beneficial treatment option for these patients. This single-center, retrospective observational study involved 18 KTRs with osteoporosis, low bone turnover, and a history of vertebral or non-vertebral fractures. Patients received teriparatide (20μg/day) for up to 2 years. Areal bone mineral density (aBMD) at the lumbar spine (LS), total hip (TH), femoral neck (FN), and trabecular bone score (TBS) were measured at baseline, 1 year, and 2 years. In addition, bone turnover markers (BTMs), serum calcium, phosphorus, parathyroid hormone (PTH), and kidney function were monitored. Significant increases in LS aBMD were observed after 1 year (0.941 ± 0.152 vs 1.043 ± 0.165, p = 0.04) and maintained after 2 years compared to baseline (0.941 ± 0.152 vs 1.074 ± 0.154, p = 0.03). TH aBMD significantly increased after 2 years (0.753 ± 0.145 vs 0.864 ± 0.141, p = 0.04), while FN and TBS showed non-significant improvement. Teriparatide was well-tolerated, with mild and transient hypercalcemia and hypophosphatemia. Teriparatide significantly improved BMD at the LS and TH in KTRs with osteoporosis and low bone turnover, showing a favorable safety profile.

The interaction between third molars and surrounding periapical tissues in mandibular stress distribution during high-impact trauma: a finite element study.

The presence of mandibular third molars has been associated with the risk of mandibular fractures, highlighting the need for comprehensive studies considering the interaction with other mandibular structures. This study investigates how mandibular third molars and neighboring tissues can influence the structural fragility of the mandible using finite element analysis. A finite element analysis study following the guidelines proposed by RIFEM 1.0 was performed using three previously created mandible models: Model A, without right and left third molars; Model B, without one third molar; Model C, with bilateral presence of third molars. A 2452N force was applied to the right mandibular body in a virtual environment, allowing for a structural analysis of each mandible. Models without third molars and with only one third molar showed similar energy dissipation patterns, contrasting with the model with both third molars. The presence of third molars influenced the magnitude and distribution of stress, highlighting fragility points in specific areas such as the lingual surface, the condyles bilaterally (models without and with one contralateral third molar to trauma), and the distal cervical region of the second molar (third molar absent), as well as significantly showed the path of energy towards the contralateral side of the trauma with a concentration of energy at the contact points of virtually all teeth present immediately after impact. The presence of mandibular third molars influenced the distribution and magnitude of stress within the mandible during a simulated high-impact trauma. Models with third molars exhibit distinct stress patterns, with fragility points appearing in critical areas such as the lingual surface, condyles, and second molar regions. These findings suggest that the presence of third molars increases the structural fragility of the mandible, potentially elevating the risk of mandibular fractures, especially in the context of traumatic impacts.

The cumulative exposure to triglyceride-glucose index and the risk of onset fragility fractures.

To investigate the association between the cumulative exposure to triglyceride-glucose index (cumTyG index) and fragility fractures in the general population. This prospective cohort study analyzed active and retired employees of Kailuan Group who participated in three consecutive health examinations in 2006, 2008 and 2010, and were followed up until 31st December 2022. The cohort comprised 55,824 participants who met the inclusion and exclusion criteria and were grouped using the cumTyG index quartiles. The outcome event was onset fragility fracture. The cumulative incidence of fragility fracture in each group was calculated by the Kaplan-Meier method, and the incidence curve was plotted. Between-group comparisons were performed using the log-rank test. A Cox regression model was used to analyze the hazard ratio (HR) and 95 % confidence interval (CI) of fragility fractures. Nine-hundred fragility fractures occurred during a mean follow-up of 11.35 years. After multivariate Cox regression analysis and adjustment for confounders (full model), the HR (95 % CI) of the group with the highest cumTyG index compared with the group with the lowest cumTyG index was 1.30 (1.04-1.61). The risk of fragility fracture was higher in men (HR 1.37, 95 % CI 1.06-1.77) and those taking antihypertensive drugs (HR 2.47, 95 % CI 1.25-4.86). There was a linear association between the cumTyG index and the risk of fragility fracture. A high cumTyG index is a risk factor for fragility fracture and should be considered in the management of patients with high blood sugar and high cholesterol concentrations.