Enhanced fracture risk prediction: a novel multi-trait genetic approach integrating polygenic scores of fracture-related traits.

The novel metaPGS, integrating multiple fracture-related genetic traits, surpasses traditional polygenic scores in predicting fracture risk. Demonstrating a robust association with incident fractures, this metaPGS offers significant potential for enhancing clinical fracture risk assessment and tailoring prevention strategies. INTRODUCTION: Current polygenic scores (PGS) have limited predictive power for fracture risk. To improve genetic prediction, we developed and evaluated a novel metaPGS combining genetic information from multiple fracture-related traits. METHODS: We derived individual PGS from genome-wide association studies of 16 fracture-related traits and employed an elastic-net logistic regression model to examine the association between the 16 PGSs and fractures. An optimal metaPGS was constructed by combining 11 significant individual PGSs selected by the elastic regularized regression model. We evaluated the predictive power of the metaPGS alone and in combination with clinical risk factors recommended by guidelines. The discrimination ability of metaPGS was assessed using the concordance index. Reclassification was assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The metaPGS had a significant association with incident fractures (HR 1.21, 95% CI 1.18-1.25 per standard deviation of metaPGS), which was stronger than previously developed bone mineral density (BMD)-related individual PGSs. Models with PGS_FNBMD, PGS_TBBMD, and metaPGS had slightly higher but statistically non-significant c-index than the base model (0.640, 0.644, 0.644 vs. 0.638). However, the reclassification analysis showed that compared to the base model, the model with metaPGS improves the reclassification of fracture. CONCLUSIONS: The metaPGS is a promising approach for stratifying fracture risk in the European population, improving fracture risk prediction by combining genetic information from multiple fracture-related traits.

The development and validation of a prediction model for imminent vertebral osteoporotic fracture in postmenopausal women.

PURPOSE: This study aimed to develop and validate a new model that focused on the risk of imminent vertebral fractures in women with osteoporosis. METHODS: Data from 2,048 patients were extracted from three hospitals, of which 1,720 patients passed the inclusion and exclusion screen. The patients from Nanfang Hospital (NFH) were randomized at a 2:1 ratio to create a training cohort (n = 709) and an internal validation cohort (n = 355), with the patients from the other two hospitals (n = 656) used for external validation. The risk factors included in the imminent osteoporotic vertebral compression fractures (OVCFs) prediction model (labelled TVF) were sorted by the least absolute shrinkage and selection operator and constructed by logistic regression. The area under the receiver operating characteristic curve (AUC), the decision curve, and the clinical impact curves of the optimal model were analyzed to verify the model. RESULTS: There were 138 and 161 fresh fractures in NFH and the other two hospitals, respectively. The lowest BMD T value and the history of vertebral fracture were integrated into the TVF model. The prediction power of TVF was demonstrated by the AUCs of 0.788 (95% confidence interval [CI], 0.728-0.849) in the training cohort and 0.774 (95% CI, 0.705-0.842) in the internal validation cohort, and 0.790 (95% CI, 0.742-0.839) and 0.741 (95% CI, 0.668-0.813) in the external validation cohorts. CONCLUSION: The TVF model demonstrated good discrimination to stratify the imminent risk of OVCFs. We therefore consider the model as a pertinent commencement in the search for more accurate imminent OVCFs prediction.

A Computed Tomography-Based Fracture Prediction Model With Images of Vertebral Bones and Muscles by Employing Deep Learning: Development and Validation Study.

BACKGROUND: With the progressive increase in aging populations, the use of opportunistic computed tomography (CT) scanning is increasing, which could be a valuable method for acquiring information on both muscles and bones of aging populations. OBJECTIVE: The aim of this study was to develop and externally validate opportunistic CT-based fracture prediction models by using images of vertebral bones and paravertebral muscles. METHODS: The models were developed based on a retrospective longitudinal cohort study of 1214 patients with abdominal CT images between 2010 and 2019. The models were externally validated in 495 patients. The primary outcome of this study was defined as the predictive accuracy for identifying vertebral fracture events within a 5-year follow-up. The image models were developed using an attention convolutional neural network-recurrent neural network model from images of the vertebral bone and paravertebral muscles. RESULTS: The mean ages of the patients in the development and validation sets were 73 years and 68 years, and 69.1% (839/1214) and 78.8% (390/495) of them were females, respectively. The areas under the receiver operator curve (AUROCs) for predicting vertebral fractures were superior in images of the vertebral bone and paravertebral muscles than those in the bone-only images in the external validation cohort (0.827, 95% CI 0.821-0.833 vs 0.815, 95% CI 0.806-0.824, respectively; P<.001). The AUROCs of these image models were higher than those of the fracture risk assessment models (0.810 for major osteoporotic risk, 0.780 for hip fracture risk). For the clinical model using age, sex, BMI, use of steroids, smoking, possible secondary osteoporosis, type 2 diabetes mellitus, HIV, hepatitis C, and renal failure, the AUROC value in the external validation cohort was 0.749 (95% CI 0.736-0.762), which was lower than that of the image model using vertebral bones and muscles (P<.001). CONCLUSIONS: The model using the images of the vertebral bone and paravertebral muscle showed better performance than that using the images of the bone-only or clinical variables. Opportunistic CT screening may contribute to identifying patients with a high fracture risk in the future.

Prevalence of osteoporosis in older male veterans receiving hip-containing computed tomography scans: opportunistic use of biomechanical computed tomography analysis (BCT).

Osteoporosis care in men is suboptimal due to low rates of testing and treatment. Applying biomechanical computed tomography (BCT) analysis to existing CT scans, we found a high proportion of men with osteoporosis have never been diagnosed or treated. BCT may improve identification of patients at high risk of fracture. PURPOSE: Osteoporosis care in men is suboptimal due to low rates of DXA testing and treatment. Biomechanical computed tomography analysis (BCT) can be applied "opportunistically" to prior hip-containing CT scans to measure femoral bone strength and hip BMD. METHODS: In this retrospective, cross-sectional study, we used BCT in male veterans with existing CT scans to investigate the prevalence of osteoporosis, defined by hip BMD (T-score ≤ - 2.5) or fragile bone strength (≤ 3500 N). 577 men, age ≥ 65 with abdominal/pelvic CTs performed in 2017-2019, were randomly selected for BCT analysis. Clinical data were collected via electronic health records and used with the femoral neck BMD T-score from BCT to estimate 10-year hip fracture risks by FRAX. RESULTS: Prevalence of osteoporosis by BCT increased with age (13.5% age 65-74; 18.2% age 75-84; 34.3% age ≥ 85), with an estimated overall prevalence of 18.3% for men age ≥ 65. In those with osteoporosis (n = 108/577), only 38.0% (41/108) had a prior DXA and 18.6% (7/108) had received osteoporosis pharmacotherapy. Elevated hip fracture risk by FRAX (≥ 3%) did not fully capture those with fragile bone strength. In a multivariate logistic regression model adjusted for age, BMI, race, and CT location, end stage renal disease (odds ratio 7.4; 95% confidence interval 2.3-23.9), COPD (2.2; 1.2-4.0), and high-dose inhaled corticosteroid use (3.7; 1.2-11.8) were associated with increased odds of having osteoporosis by BCT. CONCLUSION: Opportunistic BCT in male veterans provides an additional avenue to identify patients who are at high risk of fractures.

Bone, cognitive, and anthropometric profiles and their relation to fracture sites in fallers: a cross-sectional study.

Risk factors involved in the different osteoporotic fracture locations are not well-known. The results of this study suggest that there is not one typical profile characterising a particular fracture site but that the occurrence of a fracture may result from the combination of different bone, cognitive, and anthropometrics characteristics. PURPOSE: Risk factors involved in the different osteoporotic fracture locations are not well-known. The aim of this study was to identify the differences in bone, cognitive, and anthropometric characteristics between different fracture sites, and to determine whether the site of a fall-related fracture is related to a specific profile. METHODS: One hundred six women aged 55 years and older with a recent fall-related fracture of the hip (n = 30), humerus (n = 28), wrist (n = 32), or ankle (n = 16) were included. Bone, cognitive, and anthropometric characteristics were first compared among the four fracture site groups. Then, a principal component analysis (PCA) was performed and a comparison was made between the four profiles identified by the first two PCA components. RESULTS: The four fracture site groups differed significantly in their education level, bone mineral density (BMD), body mass index (BMI), fear of falling, and number of errors in the Trail Making Test B, an executive function test. Each of the four fracture sites was found in each four PCA profiles, albeit with a different distribution. The profiles differed mainly by bone, cognitive, and anthropometric characteristics, but also by fear of falling. CONCLUSIONS: The fall-related fracture sites differ significantly in anthropometric and bone parameters, in fear of falling and in cognitive abilities. There is not one typical bone, cognitive, and anthropometric profile characterising a particular fall-related site, but rather several possible profiles for a given site. This suggests that the fracture site depends on a combination of several characteristics of the patient.

The clinical utility of the BMD-related comprehensive genome-wide polygenic score in identifying individuals with a high risk of osteoporotic fractures.

The potential of bone mineral density (BMD)-related genome-wide polygenic score (PGS) in identifying individuals with a high risk of fractures remains unclear. This study suggests that an efficient PGS enables the identification of strata with up to a 1.5-fold difference in fracture incidence. Incorporating PGS into clinical diagnosis is anticipated to increase the population-level screening benefits. PURPOSE: This study sought to construct genome-wide polygenic scores for femoral neck and total body BMD and to estimate their potential in identifying individuals with a high risk of osteoporotic fractures. METHODS: Genome-wide polygenic scores were developed and validated for femoral neck and total body BMD. We externally tested the PGSs, both by themselves and in combination with available clinical risk factors, in 455,663 European ancestry individuals from the UK Biobank. The predictive accuracy of the developed genome-wide PGS was also compared with previously published restricted PGS employed in fracture risk assessment. RESULTS: For each unit decrease in PGSs, the genome-wide PGSs were associated with up to 1.17-fold increased fracture risk. Out of four studied PGSs, [Formula: see text] (HR: 1.03; 95%CI 1.01-1.05, p = 0.001) had the weakest and the [Formula: see text] (HR: 1.17; 95%CI 1.15-1.19, p < 0.0001) had the strongest association with an incident fracture. In the reclassification analysis, compared to the FRAX base model, the models with [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] improved the reclassification of fracture by 1.2% (95% CI, 1.0 to 1.3%), 0.2% (95% CI, 0.1 to 0.3%), 1.4% (95% CI, 1.3 to 1.5%), and 2.2% (95% CI, 2.1 to 2.4%), respectively. CONCLUSIONS: Our findings suggested that an efficient PGS estimate enables the identification of strata with up to a 1.7-fold difference in fracture incidence. Incorporating PGS information into clinical diagnosis is anticipated to increase the benefits of screening programs at the population level.

Ethnic disparities in fracture risk assessment using polygenic scores.

Whether the PGS developed using data from European ancestry is predictive of fracture risk for minorities remains unclear. This study demonstrated that PGSs based on common BMD-related genetic variants discovered in the European ancestry cohort are predictive of fracture risk in people of Asian but not African ancestry. PURPOSE: Large-scale genome-wide association studies (GWAS) on bone mineral density (BMD) have been conducted predominantly in European cohorts. Genetic models based on common variants associated with BMD have been evaluated using almost exclusively European data, which could potentially exacerbate health disparities due to different linkage disequilibrium among different ethnic groups. METHODS: UK Biobank (UKB) is a large-scale population-based observational study starting in 2006 that recruited 502,617 individuals aged between 40 and 69 years with genotypic and phenotypic data available. Based on the summary statistics of two GWAS studies of femoral neck BMD and total body BMD, we derived four PGSs and assessed the association between each PGS and prevalent/incident fractures within each ethnic group separately using Multivariate logistic regressions and Cox proportional hazard models. All models were adjusted for age, sex, and the first four principal components. RESULTS: We assessed four PGSs derived from European cohorts. Significant associations were observed between PGSs and fracture in European and Asian cohorts but not in the African cohort. Of all four PGSs, [Formula: see text] performed the best. A standard deviation decreases in [Formula: see text] were associated with an increased hazard ratio (HR) of 1.24 (1.22-1.27), 1.28 (0.83-1.99), and 1.34 (1.10-1.64) in European, African, and Asian ancestry, respectively. A low BMD-related PGS is associated with up to 2.35- and 4.31-fold increased fracture risk in European and Asian populations. CONCLUSIONS: These results showed that PGSs based on common BMD-related genetic variants discovered in the European ancestry cohort are predictive of fracture risk in people of Asian but not African ancestry.

A systematic review on the performance of fracture risk assessment tools: FRAX, DeFRA, FRA-HS.

PURPOSE: Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. METHODS: PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59-88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. CONCLUSION: The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.

Fracture Risk Assessment and Drug Holiday in a Real-Life Setting.

PURPOSE: Describe fracture risk assessment practices among physicians treating osteoporosis in a real-life setting. METHODS: This is a retrospective cohort study in a tertiary academic center. Inclusion criteria involved adults (aged ≥18 years) who received minimum adequate therapy (bisphosphates, raloxifene, or denosumab ≥ 3 years or teriparatide ≥ 18 months). Of 1,814 charts randomly selected and reviewed, 274 patients met the inclusion criteria. Risk stratification tools included fragility fractures, Dual-energy X-ray Absorptiometry (DXA), and fracture risk assessment using the FRAX tool. Fracture risk assessment was performed before therapy initiation (N= 274) and at the time of institution of the drug holiday (N=119). High-risk patients were defined as the presence of a fragility fracture, T-score ≤-2.5, or a high-risk score by FRAX calculation. FRAX scores were independently calculated by the research team for comparison and assessment purposes. RESULTS: Before initiation of therapy (N=274) versus upon starting a drug holiday (DH; N=119), 29.9% versus 3.4% had a history of fragility fractures (P<0.001), 58.8% versus 67.2% had a DXA scan performed (P>0.05), 10.5% versus 10.9% of physicians calculated a FRAX score (P>0.05), and 71.5% versus 66.4% were considered at high risk and eligible for therapy. A DXA scan was performed after DH in 40.2% of these patients and at least once in 95.3% of the entire cohort. CONCLUSION: The reporting of FRAX score in DXA scan reports may significantly increase its utilization in fracture risk assessment. We recommend comprehensive fracture risk assessment utilizing history of prevalent osteoporosis fractures, DXA assessment, and FRAX scoring.

Dose-Dependent Association between Sarcopenia and Moderate-To-Severe Thoracic Vertebral Fragility Fracture in Older Adults.

INTRODUCTION: Sarcopenia and vertebral fracture affect a large number of older adults and can be debilitating. However, the correlation between sarcopenia and vertebral fracture has not been well studied. Thus, this study investigates the correlation between vertebral fragility fracture and the severity of sarcopenia. METHOD: This cross-sectional study included 300 community-dwelling older adults with risk higher than 10-year probability of 3% for a hip fracture and 20% for a major osteoporotic fracture by FRAX score. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus. Bone mineral density (BMD) was classified into normal or abnormal groups (T score ≤ -1.0) according to WHO criteria. Vertebral fracture was graded mild, moderate, and severe by a standardized semi-quantitative method. The association between sarcopenia and vertebral fragility fracture was investigated using a logistic regression model adjusted for confounding factors. RESULTS: Compared with the normal BMD group, the abnormal BMD group had a significantly higher prevalence of sarcopenia (7.4 vs. 26.6%, p < 0.001), poorer muscle mass (p < 0.001), and poorer hand grip (p < 0.001). The prevalence of moderate-to-severe fracture was significantly different (p = 0.006) among severe sarcopenia (16.7%), sarcopenia (6.9%), and non-sarcopenia (3.7%) for thoracic vertebrae. In the logistical regression model adjusted for confounding factors, sarcopenia plus severe sarcopenia was identified as a risk factor for moderate-to-severe thoracic vertebral fragility fracture (odds ratio [OR] = 3.29, 95% CI: 1.23-8.78, p = 0.018). We further classified the participants into normal, sarcopenia, and severe sarcopenia and found that sarcopenia and severe sarcopenia had a dose-dependent association with prevalence of thoracic vertebral fragility fractures with ORs of 2.56 (95% CI: 0.66-9.91) and 4.04 (95% CI: 1.24-13.20), respectively; p for trend = 0.014. CONCLUSION: Sarcopenia is a potential risk factor for and has a dose-dependent association with moderate-to-severe thoracic fragility fracture in older adults at increased risk for fractures.

FRAX Adjustment by Trabecular Bone Score with or Without Bone Mineral Density: The Manitoba BMD Registry.

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a FRAX®-independent risk factor for fracture. The TBS adjustment to FRAX assumes the presence of femoral neck BMD in the calculation. However, there are many individuals in whom hip DXA cannot be acquired. Whether the TBS-adjustment would apply to FRAX probabilities calculated without BMD has not been studied. The current analysis was performed to evaluate major osteoporotic fracture (MOF) and hip fracture risk adjusted for FRAX with and without femoral neck BMD. The study cohort consisted of 71,209 individuals (89.8% female, mean age 64.0 years). During mean follow-up 8.7 years, 6743 (9.5%) individuals sustained one or more incident MOF, of which 2037 (2.9%) sustained a hip fracture. Lower TBS was significantly associated with increased fracture risk when adjusted for FRAX probabilities, with a slightly larger effect when BMD was not included. Inclusion of TBS in the risk calculation gave a small but significant increase in stratification for fracture probabilities estimated with and without BMD. Calibration plots showed very minor deviations from the line of identity, indicating overall good calibration. In conclusion, the existing equations for incorporating TBS in FRAX estimates of fracture probability work similarly when femoral neck BMD is not used in the calculation. This potentially extends the range of situations where TBS can be used clinically to those individuals in whom lumbar spine TBS is available but femoral neck BMD is not available.

Dual-energy x-ray absorptiometry scanner mismatch in follow-up bone mineral density testing.

Scanner mismatch occurs frequently with follow-up dual-energy x-ray absorptiometry (DXA) scans. Nearly one-in-five follow-up DXA scans were conducted on non-cross-calibrated scanners (scanner mismatch) and more than a quarter of patients who had a follow-up DXA scan had experienced scanner mismatch. INTRODUCTION: Detecting significant changes in bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) scanners relies on the least significant change (LSC). Results from two different DXA scanners can only be compared, albeit with decreased sensitivity for change, if the LSC between the two scanners has been directly determined through cross-calibration. Performing follow-up DXA scans on non-cross-calibrated scanners (scanner mismatch) has safety and economic implications. This study aims to determine the proportion of scanner mismatch occurring at a population level. METHODS: All patients who completed at least two DXA scans between 1 April 2009 and 31 December 2018 in the province of Alberta, Canada, were identified using population-based health services databases. Scanner mismatch was defined as a follow-up DXA scan completed on a DXA scanner that differed from and was not cross-calibrated to the previous DXA scanner. Multivariate logistic regression models were used to assess predictive factors that may contribute to scanner mismatch. RESULTS: A total of 264,866 patients with 470,641 follow-up DXA scans were identified. Scanner mismatch occurred in 18.9% of follow-up DXA scans; 28.7% of patients experienced at least one scanner mismatch. Longer duration between scans (OR 1.25, 95% CI 1.24-1.26) and major osteoporotic fracture history before index scan (OR 1.06, 95% CI 1.03-1.08) increased risk of scanner mismatch. Osteoporosis medication use before index scan (OR 0.89; 95% CI 0.88-0.91), recency of follow-up scans (OR 0.98, 95% CI 0.73-0.98), female sex (OR 0.97, 95% CI 0.94-1.00), and age at last scan (OR 0.99, 95% CI 0.99-1.00) were associated with lower risk of scanner mismatch. CONCLUSION: Scanner mismatch is a common problem, occurring in one-in-five follow-up DXA scans and affecting more than a quarter of patients. Interventions to reduce this large proportion of scanner mismatch are necessary.

FREM predicts 10-year incident fracture risk independent of FRAX® probability: a registry-based cohort study.

The Danish Fracture Risk Evaluation Model (FREM) was found to predict fracture risk independent of 10-year fracture probability derived with the FRAX® tool including bone mineral density from DXA. INTRODUCTION: FREM was developed from Danish public health registers without DXA information to identify high imminent risk of major osteoporotic fracture (MOF) and hip fracture (HF), while FRAX® estimates 10-year fracture probability from clinical risk factors and femoral neck bone mineral density (BMD) from DXA. The FREM algorithm showed significant 1- and 2-year fracture risk stratification when applied to a clinical population from Manitoba, Canada. We examined whether FREM predicts 10-year fracture risk independent of 10-year FRAX probability computed with BMD. METHODS: Using the Manitoba BMD Program registry, we identified women and men aged ≥ 45 years undergoing baseline BMD assessment. We calculated FREM and FRAX scores, and identified incident fractures over 10 years. Hazard ratios (HRs) for incident fracture were estimated according to FREM quintile, adjusted for FRAX probability. We compared predicted with observed 10-year cumulative fracture probability estimated with competing mortality. RESULTS: The study population comprised 74,446 women, mean age 65.2 years; 7945 men, mean age 67.5 years. There were 7957 and 646 incident MOF and 2554 and 294 incident HF in women and men, respectively. Higher FREM scores were associated with increased risk for MOF (highest vs middle quintile HRs 1.49 women, 2.06 men) and HF (highest vs middle quintile HRs 2.15 women, 2.20 men) even when adjusted for FRAX. Greater mortality with higher FREM scores attenuated its effect on 10-year fracture probability. In the highest FREM quintile, observed slightly exceeded predicted 10-year probability for MOF (ratios 1.05 in women, 1.49 in men) and HF (ratios 1.29 in women, 1.34 in men). CONCLUSIONS: Higher FREM scores identified women and men at increased fracture risk even when adjusted for FRAX probability that included BMD; hence, FREM provides additional predictive information to FRAX. FRAX slightly underestimated 10-year fracture probability in those falling within the highest FREM quintile.

Accuracy of the Fracture Risk Assessment Tool for judging pharmacotherapy initiation for primary osteoporosis.

INTRODUCTION: This study aimed to determine whether the Fracture Risk Assessment Tool (FRAX®) is useful in assessing the criteria for the initiation of pharmacotherapy for primary osteoporosis based on the current diagnostic criteria in Japan. MATERIALS AND METHODS: We enrolled 614 patients aged ≥ 40 years (average, 77.0 years) who were eligible for primary osteoporosis evaluation. Bone mineral density measurements of the lumbar spine, total hip, and femoral neck using ALPHYS LF (FUJIFILM, Tokyo, Japan) and imaging studies involving the lumbar spine were obtained and the FRAX® scores of each patient were calculated with and without the T-score of the femoral neck. The receiver operating characteristic curve analysis method was used to calculate the cut-off FRAX® scores with reference to the criteria for initiating pharmacotherapy for osteoporosis; the accuracies of both FRAX® scores were compared. RESULTS: The FRAX® score calculated with the T-score was more accurate for hip fracture risk assessment [cut-off value 5.5%; the area under the curve (AUC) 0.946] than for major osteoporotic fracture risk assessment (cut-off value 17.0%; AUC 0.924) in judging the criteria (p = 0.001). Conversely, the FRAX® score calculated without the T-score was equally accurate for hip fracture risk assessment (AUC 0.796) and major osteoporotic fracture risk assessment (AUC 0.806) (p = 0.23). CONCLUSION: The FRAX® score can accurately assess the criteria for initiating pharmacotherapy for primary osteoporosis based on the current Japanese diagnostic criteria, especially when the T-score is used.

Trabecular Bone Score in Rheumatic Disease.

PURPOSE OF REVIEW: Patients with rheumatic disease are at high risk of low bone mass and osteoporotic fracture. Trabecular bone score (TBS), derived from lumbar spine dual-energy x-ray absorptiometry (DXA), is a novel measure of bone texture that independently predicts fracture risk. This review examines the role of TBS in rheumatic disease including fracture prediction. RECENT FINDINGS: Most studies concerning TBS and rheumatic disease are cross-sectional, with consistent evidence of lower TBS in patients with rheumatic disease compared to controls. Recent studies have shown association and predictive ability of TBS for prevalent fracture, and the few longitudinal studies showed predictive ability of TBS for incident fracture. TBS in ankylosing spondylitis is of interest given the high rates of vertebral fracture and technical difficulty with lumbar spine bone mineral density. TBS degradation has been associated with disease activity in ankylosing spondylitis, systemic sclerosis, and rheumatoid arthritis. Glucocorticoid exposure is associated with lower TBS, and predicts prevalent fracture, in patients with rheumatic conditions.

Hospital-Wide Surveillance of Fracture Risk Assessment by Both FRAX and Medication Patterns in Acute Care Hospital.

To identify patients at a high risk for primary and secondary osteoporotic fractures using fracture risk assessments performed using the current method and the proposed method, in an acute care hospital and to identify departments where high-risk patients are admitted. This retrospective study included patients aged 40-90 years who were hospitalized at Fujita Health University Hospital. We collated the clinical data and prescriptions of all study participants. We also gathered data pertaining to risk factors according to Fracture Risk Assessment Tool (FRAX). Of the 1595 patients, the mean number of major osteoporotic fracture risk predicted using FRAX was 11.73%. The department of rheumatology showed the highest fracture risk (18.55 ± 16.81) and had the highest number of patients on medications that resulted in reduced bone mineral density (1.07 ± 0.98 medication). Based on the FRAX, the proportion of patients in the high-risk group in this department was significantly higher compared with those in the remaining departments with respect to glucocorticoid administration, rheumatoid arthritis, and secondary osteoporosis. However, the departments included in the high-risk group were not necessarily the same as the departments included in the top group, based on the administered medications. FRAX score is calculated based on various risk factors; however, only glucocorticoid corresponds to medications. We should focus on medication prescription patterns in addition to FRAX to improve fracture risk assessment in hospital-wide surveillance. Therefore, we recommend the use of FRAX along with the prescribed medications to identify departments that admit high-risk patients.

Pulse-Echo Measurements of Bone Tissues. Techniques and Clinical Results at the Spine and Femur.

The aim of this chapter is to review the available pulse-echo approaches for the quantitative evaluation of bone health status, with a specific application to the assessment of possible osteoporosis presence and to the fracture risk prediction. Along with a review of the main in-vivo imaging approaches for skeletal robustness evaluation and fracture risk assessment, further understanding into Radiofrequency Echographic Multi Spectrometry (REMS), an ultrasound-based method measuring clinically relevant bone districts (i.e. lumbar vertebrae and proximal femur), is provided, and the further potentialities of this technology are discussed.Currently, the bone mineral density (BMD) provided by dual X-ray absorptiometry (DXA) is considered an established indicator for osteoporosis status assessment and fracture risk prediction, however, in order to obtain more accurate results, an additional step beyond BMD would be necessary, which means including data on bone quality for an improved evaluation of the disease and its consequences.REMS is a technology which allows both osteoporosis diagnosis, through the BMD estimation, and the prediction of fracture risk, through the computation of the Fragility Score; both measures are obtained by the automatic processing of unfiltered ultrasound signals acquired in correspondence of anatomical reference sites.

Fracture rates in patients discontinuing alendronate treatment in real life: a population-based cohort study.

In this nationwide register-based cohort study, we found no difference in the risk of fractures in patients discontinuing versus continuing alendronate (ALN) treatment after 5 years. INTRODUCTION: Information on fracture risk in patients discontinuing ALN in a real-life setting is sparse. We aimed to examine ALN discontinuation patterns, compare fracture rates in patients discontinuing versus continuing ALN after 5 years of treatment, and define determinants of fractures in ALN discontinuers. METHODS: A nationwide population-based cohort study using Danish health registry data. Our source population was individuals who had redeemed ≥ 2 ALN prescriptions between January 1, 1995, and September 1, 2017. RESULTS: We found that 25% of all ALN initiators used ALN for less than 1 year and 43% continued treatment for at least 5 years. We classified n = 1865 as ALN discontinuers and n = 29,619 as ALN continuers. Using Cox proportional hazards regression analysis and an "as-treated" approach, we observed no increased risk of any fracture (incidence rate ratio (IRR) 1.06, 95% CI 0.92-1.23), vertebral fracture (IRR 0.59, 95% CI 0.33-1.05), hip fracture (IRR 1.04, 95% CI 0.75-1.45), or major osteoporotic fracture (IRR 1.05, 95% CI 0.88-1.25) in the ALN discontinuers compared to continuers during a follow-up time of 1.84 ± 1.56 years (mean ± SD) and 2.51 ± 1.60 years, respectively. ALN re-initiation was a major determinant of follow-up among the discontinuers. Old age (> 80 vs. 50-60 years, unadjusted IRR 2.92, 95% CI 1.18-7.24) was the strongest determinant for fractures following ALN discontinuation. CONCLUSION: In a real-world setting, less than 50% continued ALN treatment for 5 years. We found no difference in the risk of fractures in patients discontinuing versus continuing ALN after 5 years.

Pharmacotherapy decisions among postmenopausal women attending a group medical consultation or a one-on-one specialist consultation at an osteoporosis center: an observational cohort study.

Group medical visits for osteoporosis can improve access to care while being highly accepted by patients. In this study, a similar proportion of women planned to initiate pharmacotherapy after attending a group or traditional one-on-one osteoporosis consultation, indicating that the group consultation model does not produce unexpected treatment decisions. INTRODUCTION: Group medical consultations for osteoporosis are time-efficient and highly accepted by patients, but effects on treatment decisions are unknown. We aimed to compare women's decisions to initiate or decline osteoporosis pharmacotherapy after attending either a group or transitional one-on-one osteoporosis consultation. METHODS: In this observational study, we prospectively evaluated postmenopausal women referred to an osteoporosis clinic who attended a group medical visit and compared their decisions regarding pharmacologic osteoporosis treatment with retrospective data from a cohort of women who attended a traditional consultation. Both consultation types involved interaction with a specialist physician, individualized fracture risk estimation (using FRAX®), and education regarding fracture consequences and available osteoporosis medications. Both forms of consultation emphasized shared decision-making; however, group consultation attendees did not receive personalized treatment recommendations from the physician. RESULTS: We reviewed the records of 125 women (median age 63 years) who attended a group consultation and 83 women (median age 64 years) who attended a traditional consultation between 2016 and 2019. Twenty-four (19%) of the group cohort and 16 (19%) of the traditional cohort were at high 10-year risk of major osteoporotic fracture (FRAX® ≥ 20.0%). A similar proportion planned to initiate pharmacologic therapy after the group and traditional consultations (23% vs 16%, p = 0.22); these proportions were comparable among women at high risk (42% vs 50%, p = 0.75) and moderate risk (19% vs 15%, p = 0.77), but a higher proportion of low-risk women planned to initiate therapy after the group consultation (18% vs 0%, p = 0.009). CONCLUSION: Patient decisions to initiate pharmacologic treatment made during a group visit are similar to those made during traditional one-on-one consultation. The group consultation model represents an alternative to one-on-one assessment for delivering osteoporosis consultative services.

Regional and gender-specific analyses give new perspectives for secular trend in hip fracture incidence.

In this study, we found that regional disparity in incidence of hip fractures has converged. Also, annual hip fracture risk ratios between genders have systematically diminished over time. INTRODUCTION: Several studies have reported secular trends in hip fracture incidence, but knowledge about the possible causes is limited. We studied potential explanations by examining spatio-temporal epidemiology of the fractures and estimating relative risks between genders. METHODS: This observational study was based on all inpatient hospital discharges in 1972-2018 in Finland. We divided the data by gender, 5-year age groups and Finnish sub-regions and estimated gender and age standardized spatio-temporal rates of hip fractures by using a Bayesian age-period-cohort model. RESULTS: In 1972, women's hip fracture incidence was 1.2-1.3 times higher in western and coastal Finland compared to eastern and inland areas. Also, women had approximately 1.7 times higher average risk to get a hip fracture compared to men. Today, the hip fracture differences between the areas have converged to insignificant and the relative risk between genders has diminished to 1.2. Age-specific relative risks indicate greater hip fracture risk for younger men and older women, and the women's risk increases beyond the risk of men at age 65 which is ten years later than in the beginning of the study period. CONCLUSION: Incidence of hip fracture has converged significantly between regions and genders. Especially factors related with socioeconomic development and increased frailty and longevity seem to be important. The hip fracture incidence rate ratio between women and men has systematically decreased in time, and more attention should be paid to hip fracture risk in men in the future.