Ten-year fracture risk in Japanese patients with myasthenia gravis: A comprehensive assessment using the fracture risk assessment tool.

BACKGROUND: Myasthenia gravis (MG) is an immune disorder that causes muscle weakness with an increasing prevalence, particularly among the elderly in Japan. Glucocorticoid treatment for MG is problematic for bone health because of reduced bone density and increased fracture risk. The fracture risk assessment tool (FRAX®) can estimate fracture risk, but its applicability in patients with MG remains uncertain. METHODS: A prospective cohort study was conducted on 54 patients with MG between April and July 2012. Bone mineral density (BMD) was measured, and FRAX® scores were calculated with and without BMD. We also adjusted FRAX® scores based on glucocorticoid dosage. Patients were monitored for major osteoporotic fractures (MOF) until June 2022. Statistical analyses included Kaplan-Meier curves and Cox proportional hazards models. RESULTS: The study group included 12 men and 42 women with a mean age of 62 years. Higher FRAX® scores correlated with increased fracture risk, particularly in the hip and lumbar regions. The 10-year fracture-free rate was significantly lower in the high-FRAX® score group. The FRAX® score using BMD is a significant predictor of MOF risk. The hazard ratio for FRAX® scores was 1.17 (95% CI 1.10-1.26). CONCLUSION: We demonstrated the effectiveness of the FRAX® tool in assessing fracture risk among patients with MG. High FRAX® scores correlated with increased fracture risk, emphasizing its importance. These findings support the incorporation of FRAX® assessment into clinical management to enhance patient care and outcomes. However, the small sample size and observational nature suggest a need for further research.

Real world fracture prediction of fracture risk assessment tool (FRAX), osteoporosis self-assessment tool for Asians (OSTA) and one-minute osteoporosis risk test: An 11-year longitudinal study.

Introduction: Fractures affect people's quality of life especially in the elders. One of the most important risk factors is osteoporosis. There are many screening tools to predict osteoporosis and fractures. We aimed to compare the predictive validity of three commonly used screening tools: fracture risk assessment tool (FRAX), osteoporosis self-assessment tool for Asians (OSTA) and one-minute osteoporosis risk test. Among them, OSTA and one-minute osteoporosis risk test were originally developed to predict osteoporosis risks and FRAX was to predict fracture risks. Methods: This is an 11-year longitudinal study. We enrolled 708 senior people from health examinees in Taiwan in 2010. A standardized questionnaire and blood tests were provided. Annual telephone interview was conducted to assess the real fracture status. We calculated risk scores of FRAX, OSTA, and one-minute osteoporosis risk test and compared with real-world fracture records. Results: The mean age of the participants were 74.9 (SD 6.4). There were 356 (50.3 %) men. From 2010 to 2020, a total of 105 (14.8 %) persons suffered from fractures. Compared to people without fractures, people with fractures had higher FRAX major osteoporotic fracture risk scores (14.0 % ± 7.6 % vs.11.3 % ± 5.7 %), higher hip fracture risk scores, and higher OSTA risk (5.9 % ± 1.4 % vs. 5.3 % ± 1.3 %). Cox regression analysis showed that hazard ratios for fracture of high FRAX risk was 1.53 (95 % confidence interval (CI) 1.05-2.21), and for high OSTA risk was 1.37 (95 % CI 1.04-1.82). Conclusions: Only OSTA and FRAX scores were satisfactory in predicting 10-year fractures.

Increased circulating microRNA-21 level as a potential indicator for predicting a higher risk of incident fragility fractures.

CONTEXT: As a common disease in the elderly, osteoporosis clearly increases the risk of fractures, leading to higher mortality, but the current markers to estimate the risk of fractures are limited. MicroRNA-21 (miR-21) may play an important role in osteoporosis, but the link of this biomarker with fractures was undetermined. OBJECTIVES: We aimed to investigate the association between miR-21 levels and the presence of fragility fractures. METHODS: A total of 200 patients were recruited and miR-21 was collected from baseline serum. The correlation between miR-21 and the fracture risk assessment tool (FRAX) score was analyzed. The incidence of fragility fractures was presented by Kaplan-Meier analysis, and Cox regression analysis was utilized to evaluate risk factors. The diagnostic value of miR-21 was conducted by the area under curve (AUC). RESULTS: The FRAX score was significantly associated with miR-21 level (p<0.001). According to the 50th percentile of miR-21 content in the overall distribution, the cumulative incidence of fragility fractures was significantly higher in patients with higher miR-21 levels than those with lower levels (75.4, 95 % CI: 69.0-81.8 vs. 59.2, 95 % CI: 42.1-76.3, p<0.001). The results of the Cox regression analysis showed that the miR-21 level was an independent risk factor linked to the incidence of fracture (p=0.005). The optimal cut-off value of the miR-21 was 6.08, and the AUC for predicting fracture was 0.718 (95 % CI, 0.645-0.790). CONCLUSIONS: This study showed that miR-21 has optimal diagnostic performance in the discrimination of fragility fracture, and the circulating miR-21 level in predicting the risk of fragility fracture may have a certain value.

Assessment for bone health in patients with differentiated thyroid carcinoma after postoperative thyroid-stimulating hormone suppression therapy: a new fracture risk assessment algorithm.

Purpose: The fracture risk assessment tool (FRAX) is used to assess the 10-year risk of major site and hip fractures; however, whether this tool can be applied to patients receiving levothyroxine-based thyroid-stimulating hormone (TSH) suppressive therapy for postoperative differentiated thyroid cancer (DTC) patients is yet to be clarified. Methods and design: A total of 64 patients with DTC following thyroidectomy and oral levothyroxine for TSH suppression therapy and 30 gender- and age-matched controls were collected. The fracture risk was compared between the affected groups with different TSH levels. FRAX was used to calculate the fracture risk with and without bone mineral density (BMD). The TSH level was converted to an age-weighted score to estimate the fracture risk of postoperatively differentiated thyroid cancer patients. The sensitivity, specificity, and area under the AUC curve of the traditional FRAX and the new algorithm for osteoporosis diagnosis were compared. The dual-energy X-ray bone mineral density measurement T score was used as the gold standard to diagnose osteoporosis. Results: There were 24 patients in the T ≥ -1-2.5 group, 23 in the -2.5 < T < -1 group, and 17 in the T ≤ -2.5 group. The T score of BMD in the disease group was significantly lower than that in the control group (p < 0.05). The risk of MOF and hip fracture without a T score were significantly different under various TSH levels (p < 0.05). The area under the curve (AUC) of FRAX without BMD for predicting major osteoporotic fractures (PMOF) and major hip fractures (PHF) was 0.694 and 0.683, respectively. The cutoff values were 2.15% and 0.25%, respectively. The AUC of FRAX with BMD for PMOF and PHF was 0.976 and 0.989, respectively, and the cutoff values were 4.15% and 1.1%, respectively. The AUC of FRAX without BMD for PMOF and PHF was 0.708 and 0.72, respectively, and the cutoff values were 5.5% and 1.55%, respectively. Conclusions: FRAX is suitable for postoperative DTC patients after TSH suppressive therapy. In the absence of BMD, TSH weighted by age can improve the specificity of FRAX in the diagnosis of osteoporosis in this population.

Prevalence of FRAX risk factors and the osteoporosis treatment gap among women ≥ 70 years of age in routine primary care across 8 countries in Europe.

We studied whether elderly women at risk for fractures receive primary care treatment to prevent fracture. We found that across Europe, women at risk are often not identified, and less than half of such women receive appropriate treatment. Finally, women diagnosed with osteoporosis are much more likely to receive treatment. PURPOSE: To examine the relationship between risk factors for fragility fracture (FF) and osteoporosis (OP) treatment gap in elderly women across Europe, and compare the prevalence of risk factors between countries. METHODS: Demographic and clinical information was collected from women ≥ 70 years visiting primary care physicians in Belgium, France, Germany, Ireland, Poland, Slovakia, Switzerland, and the UK. Increased risk of FF was defined by the presence of 1 or more criteria (history of fracture, 10-year fracture probability, or T-score ≤ - 2.5). RESULTS: There were 3798 women in total. Treatment gap (proportion at increased risk of FF not receiving treatment for OP) varied from 53.1 to 90.8% across countries, and the proportion of patients at increased risk of FF varied from 41.2 to 76.1%. Across countries, less than 50% of patients with increased risk of FF had a diagnosis of OP. Previous fracture was the most common risk factor, with similar prevalence across most countries; other risk factors varied widely. The treatment gap was reduced in patients with an OP diagnosis in all countries, but this reduction varied from 36.5 to 79.4%. The countries with the lowest rates of bone densitometry scans (Poland, France, and Germany; 8.3-12.3%) also had the highest treatment gap (82.2 to 90.8%). CONCLUSIONS: This study highlights differences across Europe in clinical risk factors for fracture, rates of densitometry scanning, and the rates of OP diagnosis. More emphasis is needed on risk assessment to improve the identification and treatment of elderly women at risk for fracture.

The Utility of Genetic Risk Score to Improve Performance of FRAX for Fracture Prediction in US Postmenopausal Women.

The ability of the fracture risk assessment tool (FRAX) in discriminating fracture and non-fracture in postmenopausal women remains suboptimal. Adding a genetic profile may improve the performance of FRAX. Three genetic risk scores (GRSs) (GRS_fracture, GRS_BMD, GRS_eBMD) were calculated for each participant in the Women's Health Initiative Study (n = 23,981), based on the summary statistics of three comprehensive osteoporosis-related genome-wide association studies (GWAS). The primary outcomes were incident major osteoporotic fracture (MOF) and hip fracture (HF). The association between each GRS and fracture risk were evaluated in separate Cox Proportional Hazard models, with FRAX clinical risk factors adjusted for. The discrimination ability of each model was assessed using Area Under the Curve (AUC). The predictive improvement attributable to each GRSs was assessed using the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). GRS_BMD and GRS_eBMD were significantly associated with MOF and HF risk, independent of the base FRAX risk factors. Compare to the base FRAX model, the models with GRS_fracture, GRS_BMD, and GRS_eBMD improved the reclassification of MOF by 0.5% (95% CI, 0.2% to 0.9%, p = p < .01), 0.3% (95% CI, 0.1% to 0.6%, p = 0.01), and 2.1% (95% CI, 0.3% to 2.8%, p < .01), respectively. Similar results were also observed when using HF as an outcome. Our study suggested that the addition of genetic profiles provide limited improvements in the reclassification of FRAX for MOF and HF.

Performance of FRAX in Predicting Fractures in US Postmenopausal Women with Varied Race and Genetic Profiles.

BACKGROUND: Whether the Fracture Risk Assessment Tool (FRAX) performed differently in estimating the 10-year fracture probability in women of different genetic profiling and race remained unclear. METHODS: The genomic data in the Women's Health Initiative (WHI) study was analyzed (n = 23,981). The genetic risk score (GRS) was calculated from 14 fracture-associated single nucleotide polymorphisms (SNPs) for each participant. FRAX without bone mineral density (BMD) was used to estimate fracture probability. RESULTS: FRAX significantly overestimated the risk of major osteoporotic fracture (MOF) in the WHI study. The most significant overestimation was observed in women with low GRS (predicted/observed ratio (POR): 1.61, 95% CI: 1.45-1.79) specifically Asian women (POR: 3.5, 95% CI 2.48-4.81) and in African American women (POR: 2.59, 95% CI: 2.33-2.87). Compared to the low GRS group, the 10-year probability of MOF adjusted for the FRAX score was 21% and 30% higher in the median GRS group and high GRS group, respectively. Asian, African American, and Hispanic women respectively had a 78%, 76%, and 56% lower hazard than Caucasian women after the FRAX score was adjusted. The results were similar for hip fractures. CONCLUSIONS: Our study suggested the FRAX performance varies significantly by both genetic profile and race in postmenopausal women.

Advances in Predicting Fracture Risk Based on Hip Bone Properties / 医用生物力学

With the increasing life span of the population and the increasing proportion of the elderly population, the elderly with osteoporosis are prone to hip fractures, which brings heavy economic burdens to the family and society. The progress in predicting hip fractures from the aspects of the proximal femur geometry, bone mineral density (BMD), fracture risk assessment tool (FRAX) and finite element analysis (FEA) based on computed tomography (CT) imaging was reviewed, in order to understand the influencing factors of fracture risk, improve the accuracy of hip fracture risk prediction for the elderly, detect the high fracture risk group at an early stage, and hence to reduce the occurrence of fractures with appropriate preventing measures, and provide theoretical references for the prevention and treatment of hip fractures.

The utility of dual-energy X-ray absorptiometry, calcaneal quantitative ultrasound, and fracture risk indices (FRAX® and Osteoporosis Risk Assessment Instrument) for the identification of women with distal forearm or hip fractures: A pilot study.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is considered the "gold standard" in predicting osteoporotic fractures. Calcaneal quantitative ultrasound (QUS) variables are also known to predict fractures. Fracture risk assessment tools may also guide us for the detection of individuals at high risk for fractures. The aim of this case-control study was to evaluate the utility of DXA bone mineral density (BMD), calcaneal QUS parameters, FRAX® (Fracture Risk Assessment Tool), and Osteoporosis Risk Assessment Instrument (ORAI) for the discrimination of women with distal forearm or hip fractures. MATERIALS AND METHODS: This case-control study included 20 women with a distal forearm fracture and 18 women with a hip fracture as cases and 76 age-matched women served as controls. BMD at the spine, proximal femur, and radius was measured using DXA and acoustic parameters of bone were obtained using a calcaneal QUS device. FRAX® 10-year probability of fracture and ORAI scores were also calculated in all participants. Receiver operating characteristic (ROC) analysis was used to assess fracture discriminatory power of all the tools. RESULTS: While all DXA BMD, and QUS variables and FRAX® fracture probabilities demonstrated significant areas under the ROC curves for the discrimination of hip-fractured women and those without, only 33% radius BMD, broadband ultrasound attenuation (BUA), and FRAX® major osteoporotic fracture probability calculated without BMD showed significant discriminatory power for distal forearm fractures. CONCLUSIONS: It can be concluded that QUS variables, particularly BUA, and FRAX® major osteoporotic fracture probability without BMD are good candidates for the identification of both hip and distal forearm fractures.

Can Hip Fracture Prediction in Women be Estimated beyond Bone Mineral Density Measurement Alone?

The etiology of hip fractures is multifactorial and includes bone and fall-related factors. Low bone mineral density (BMD) and BMD-related and BMD-independent geometric components of bone strength, evaluated by hip strength analysis (HSA) and finite element analysis analyses on dual-energy X-ray absorptiometry (DXA) images, and ultrasound parameters are related to the presence and incidence of hip fracture. In addition, clinical risk factors contribute to the risk of hip fractures, independent of BMD. They are included in the fracture risk assessment tool (FRAX) case finding algorithm to estimate in the individual patient the 10-year risk of hip fracture, with and without BMD. Fall risks are not included in FRAX, but are included in other case finding tools, such as the Garvan algorithm, to predict the 5- and 10-year hip fracture risk. Hormones, cytokines, growth factors, markers of bone resorption and genetic background have been related to hip fracture risk. Vitamin D deficiency is endemic worldwide and low serum levels of 25-hydroxyvitamin D [25(OH)D] predict hip fracture risk. In the context of hip fracture prevention calculation of absolute fracture risk using clinical risks, BMD, bone geometry and fall-related risks is feasible, but needs further refinement by integrating bone and fall-related risk factors into a single case finding algorithm for clinical use.