Fracture Risk Prediction Research Articles

Conceptual design of the dual X-ray absorptiometry health informatics prediction system for osteoporosis care.

Osteoporotic fractures are a major and growing public health problem, which is strongly associated with other illnesses and multi-morbidity. Big data analytics has the potential to improve care for osteoporotic fractures and other non-communicable diseases (NCDs), reduces healthcare costs and improves healthcare decision-making for patients with multi-disorders. However, robust and comprehensive utilization of healthcare big data in osteoporosis care practice remains unsatisfactory. In this paper, we present a conceptual design of an intelligent analytics system, namely, the dual X-ray absorptiometry (DXA) health informatics prediction (HIP) system, for healthcare big data research and development. Comprising data source, extraction, transformation, loading, modelling and application, the DXA HIP system was applied in an osteoporosis healthcare context for fracture risk prediction and the investigation of multi-morbidity risk. Data was sourced from four DXA machines located in three healthcare centres in Ireland. The DXA HIP system is novel within the Irish context as it enables the study of fracture-related issues in a larger and more representative Irish population than previous studies. We propose this system is applicable to investigate other NCDs which have the potential to improve the overall quality of patient care and substantially reduce the burden and cost of all NCDs.

Skip that repeat DXA scan in these postmenopausal women.

Repeat bone density measurement offers no advantage in predicting fracture risk in postmenopausal women who do not have osteoporosis.

The Effects of Body Position on Trochanteric Soft Tissue Thickness-Implications for Predictions of Impact Force and Hip Fracture Risk During Lateral Falls.

Trochanteric soft tissue thickness (TSTT) is a protective factor against fall-related hip fractures. This study's objectives were to determine: (1)the influence of body posture on TSTT and (2)the downstream effects of TSTT on biomechanical model predictions of fall-related impact force (Ffemur) and hip fracture factor of risk. Ultrasound was used to measure TSTT in 45 community-dwelling older adults in standing, supine, and side-lying positions with hip rotation angles of -25°, 0°, and 25°. Supine TSTT (mean [SD] = 5.57 [2.8]cm) was 29% and 69% greater than in standing and side-lying positions, respectively. The Ffemur based on supine TSTT (3380 [2017]N) was 19% lower than the standing position (4173 [1764]N) and 31% lower than the side-lying position (4908 [1524]N). As factor of risk was directly influenced by Ffemur, the relative effects on fracture risk were similar. While less pronounced (<10%), the effects of hip rotation angle were consistent across TSTT, Ffemur, and factor of risk. Based on the sensitivity of impact models to TSTT, these results highlight the need for a standardized TSTT measurement approach. In addition, the consistent influence of hip rotation on TSTT (and downstream model predictions) support its importance as a factor that may influence fall-related hip fracture risk.

A transcriptome-wide association study to detect novel genes for volumetric bone mineral density.

Transcriptome-wide association studies (TWAS) systematically investigate the association of genetically predicted gene expression with disease risk, providing an effective approach to identify novel susceptibility genes. Osteoporosis is the most common metabolic bone disease, associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fractures, whereas genetic factors explain approximately 70% of the variance in phenotypes associated with bone. BMD is commonly assessed using dual-energy X-ray absorptiometry (DXA) to obtain measurements (g/cm2) of areal BMD. However, quantitative computed tomography (QCT) measured 3D volumetric BMD (vBMD) (g/cm3) has important advantages compared with DXA since it can evaluate cortical and trabecular microstructural features of bone quality, which can be used to directly predict fracture risk. Here, we performed the first TWAS for volumetric BMD (vBMD) by integrating genome-wide association studies (GWAS) data from two independent cohorts, namely the Framingham Heart Study (FHS, n=3298) and the Osteoporotic Fractures in Men (MrOS, n=4641), with tissue-specific gene expression data from the Genotype-Tissue Expression (GTEx) project. We first used stratified linkage disequilibrium (LD) score regression approach to identify 12 vBMD-relevant tissues, for which vBMD heritability is enriched in tissue-specific genes of the given tissue. Focusing on these tissues, we subsequently leveraged GTEx expression reference panels to predict tissue-specific gene expression levels based on the genotype data from FHS and MrOS. The associations between predicted gene expression levels and vBMD variation were then tested by MultiXcan, an innovative TWAS method that integrates information available across multiple tissues. We identified 70 significant genes associated with vBMD, including some previously identified osteoporosis-related genes such as LYRM2 and NME8, as well as some novel loci such as DNAAF2 and SPAG16. Our findings provide novel insights into the pathophysiological mechanisms of osteoporosis and highlight several novel vBMD-associated genes that warrant further investigation.

Peripheral quantitative computed tomography (pQCT) measures are associated with prior low trauma fracture in men.

Peripheral quantitative computed tomography (pQCT) provides information about bone structure and density complementary to dual x-ray absorptiometry. This study aimed to determine which pQCT parameters are associated with prior fracture. Participants were men (n = 508, age 33-96years) from the Geelong Osteoporosis Study. Parameters at 4% (n = 469) and 66% (n = 436) of radial length, and 4% (n = 449) and 66% (n = 437) of tibial length were acquired (pQCT XCT 2000, Stratec Medizintechnik, Pforzheim, Germany), and mean standardised. Low trauma prior fractures in adulthood (≥ age 20years) were radiologically confirmed when possible. Cross-sectional associations between pQCT and fracture were tested using logistic regression adjusting for confounders. Prior low trauma fractures were identified for 106 participants. Fracture was negatively associated with parameters at the 4% radius site: bone mass (adjusted OR = 0.67; 95%CI = 0.52-0.86), total density (OR = 0.61; 95%CI = 0.47-0.78), trabecular density (OR = 0.62; 95%CI = 0.48-0.79) and cortical subdensity (OR = 0.61; 95%CI = 0.47-0.77). At the 66% radius site, fracture was associated with total density (OR = 0.69; 95%CI = 0.55-0.87) and cortical thickness (OR = 0.68; 95%CI = 0.54-0.86). Fracture was associated with the ratio of the cortical area at the 66% site to the total area at the 4% site (OR = 0.74; 95%CI = 0.58-0.94). Prior fracture was negatively associated with parameters at the 4% tibial site: total density (OR = 0.67; 95%CI = 0.52-0.86), trabecular density (OR = 0.64; 95%CI = 0.50-0.82) and cortical subdensity (OR = 0.72; 95%CI = 0.56-0.92). Fracture was negatively associated with cortical density at the 66% site (OR = 0.74; 95%CI = 0.58-0.94), and the ratio of the cortical area at the 66% site to the total area at the 4% site (OR = 0.65; 95%CI = 0.46-0.91), but were attenuated in adjusted models. No other associations were identified. Prior fracture was associated with parameters at both the radius and tibia. This study highlights key pQCT parameters that may aid in the prediction of fracture risk.

Bone fracture healing within a continuum bone remodelling framework

Bone fracture healing is a complex process which is still under research. Computer-aided patient-specific prediction of bone development, fracture risk, prevention and treatment approaches promises a significant milestone in clinical practice. With this long-term goal in mind, a novel model is presented and examined in this work in the context of continuum bone remodelling. Therein, a clear distinction is made between external mechanical stimulation and the biological healing process of an injured bone tissue. The model is implemented within a finite element framework and investigated for the example of a fractured proximal femur head. The results show promising perspectives for further application. Besides, the model offers the possibility of easily integrating other factors like age-dependency and the availability of nutrition. For the future, further studies with large clinical datasets are essential for validation.

Applications of Machine Learning in Bone and Mineral Research.

In this unprecedented era of the overwhelming volume of medical data, machine learning can be a promising tool that may shed light on an individualized approach and a better understanding of the disease in the field of osteoporosis research, similar to that in other research fields. This review aimed to provide an overview of the latest studies using machine learning to address issues, mainly focusing on osteoporosis and fractures. Machine learning models for diagnosing and classifying osteoporosis and detecting fractures from images have shown promising performance. Fracture risk prediction is another promising field of research, and studies are being conducted using various data sources. However, these approaches may be biased due to the nature of the techniques or the quality of the data. Therefore, more studies based on the proposed guidelines are needed to improve the technical feasibility and generalizability of artificial intelligence algorithms.

Prediction of imminent fracture risk in Canadian women and men aged 45years or older: external validation of the Fracture Risk Evaluation Model (FREM).

The FREM is a tool developed from Danish public health registers (hospital diagnoses) to identify individuals over age 45years at high imminent risk of major osteoporotic fractures (MOF) and hip fracture (HF). In this study, our aim was to examine the ability of FREM to identify individuals at high imminent fracture risk in women and men from Manitoba, Canada. We used the population-based Manitoba Bone Mineral Density (BMD) Program registry, and identified women and men aged 45years or older undergoing baseline BMD assessment with 2years of follow-up data. From linked population-based data sources, we constructed FREM scores using up to 10years of prior healthcare information. The study population comprised 74,828 subjects, and during the 2years of observation, 1612 incident MOF and 299 incident HF occurred. We found significant fracture risk stratification for all FREM scores, with AUC estimates of 0.63-0.66 for MOF for both sexes and 0.84 for women and 0.65-0.67 for men for HF. FREM performed better than age alone but not as well as FRAX® with BMD. The inclusion of physician claims data gave slightly better performance than hospitalization data alone. Overall calibration for 1-year MOF prediction was reasonable, but HF prediction was overestimated. In conclusion, the FREM algorithm shows significant fracture risk stratification when applied to an independent clinical population from Manitoba, Canada. Overall calibration for MOF prediction was good, but hip fracture risk was systematically overestimated indicating the need for recalibration.

The influence of snuff and smoking on bone accretion in late adolescence. The Troms\xf8 study, Fit Futures

SummaryAreal bone mineral density (aBMD) predicts future fracture risk. This study explores associations between use of tobacco and bone accretion in Norwegian adolescents. Our results indicate that use of snuff is negatively associated with accretion of aBMD in adolescence and may be a signal of increased future fracture risk.PurposeBone mineral accrual in childhood and adolescence is a long-term primary preventive strategy of osteoporosis. Areal bone mineral density (aBMD) is a surrogate measure of bone strength and a predictor of fracture risk. The aim of this population-based 2-year follow-up cohort study was to explore associations between use of snuff and smoking and changes (∆) in aBMD in Norwegian girls and boys aged 15–17 years at baseline.MethodsThe first wave of the Tromsø study, Fit Futures was conducted from 2010 to 2011. Femoral neck (FN), total hip (TH), and total body (TB) bone mineral content (BMC) and aBMD were measured by dual-energy X-ray absorptiometry. Information on use of snuff, smoking habits, and other lifestyle related variables were collected through self-administered questionnaires. Two years later, during 2012–2013, the measurements were repeated in the second wave. The present study included 349 girls and 281 boys and compared “non-users” (n = 243 girls, 184 boys) with “users” (n = 105 girls, 96 boys) of snuff and “non-smokers” (n = 327 girls, 249 boys) with “smokers” (n = 21 girls, 31 boys) using linear regression adjusted for age, baseline height and weight, change in height and weight, pubertal maturation, physical activity, ethnicity, alcohol consumption, diagnosis known to affect bone, and medication known to affect bone. The influence of “double use” on bone accretion was also explored.ResultsIn girls, no associations between use of snuff and ∆aBMD were found. In boys, use of snuff was associated with reduced bone accretion in all ∆aBMD models. Sensitivity analysis with exclusion of “sometimes” users of snuff strengthened associations at femoral sites in girls and attenuated all associations in boys. In girls, no associations between smoking and ∆aBMD were found. In boys, only the association with TB ∆aBMD was significant in the fully adjusted models. In girls, “double users” analyses showed similar association to smoking. In boys, nearly all models showed statistically significant associations with a difference of ~ 1–2% in ∆aBMD between “non-users” and “double users” during 2 years of follow-up.ConclusionsOur results indicate that tobacco use in late adolescence could be detrimental to bone accretion and may be a signal of increased fracture risk in adult life.

One leg standing time predicts fracture risk in older women independent of clinical risk factors and BMD

SummaryIn women of ages 75–80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women.IntroductionPhysical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women.MethodsThe Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75–80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed.ResultsDuring a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49–6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34–1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26–2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s).ConclusionA low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women.

Comparison of Trabecular Bone Score-Adjusted FRAX™ and FRAX™-Bone Mineral Density in Postmenopausal Women with Clinical Vertebral Fractures: A Cross-Sectional, Analytic Study

Background: Ethnicity differentially modulate fracture risk prediction using FRAX™-bone mineral density (BMD). Objective: To compare FRAX™-BMD and trabecular bone score (TBS)-adjusted FRAX™ in the 10-year probability of fracture among Thai postmenopausal woman (PMW) with vertebral fracture (VF). Materials and Methods: The present study was a cross-sectional study conducted by retrospective review of medical records of PMW with VF older than 45 years undergoing lumbar and hip DXA scan. The authors excluded the PMW having been treated with metal implant at the spine, 3 or more lumbar VF, or cancer spreading to vertebral spine. The authors assessed the difference in means of normally distributed data by dependent sample t-test, the correlation between TBS and LS BMD by Pearson correlation, and the difference in proportions of PMW who met intervention threshold (IT) before and after TBS-adjusted FRAX™ by McNemar’s test. A p&lt;0.05 was considered statistically significant. Results: Of the 119 patients, the mean age was 70.8±8.1 years. The mean 10-year probability of a hip fracture by TBS-adjusted FRAX™ was significantly higher than that by FRAX™-BMD with the mean difference of 0.44% (95% CI 0.13 to 0.76). The higher difference in means, using TBSadjusted FRAX™, was even significantly greater in the 10-year probability of major osteoporotic fractures. For either the IT of major osteoporotic fracture or hip fracture, TBS-adjusted FRAX™ resulted in four added PMWs who needed treatment, but without statistical significance. Conclusion: TBS-adjusted FRAX™ had a higher 10-year probability of fracture than FRAX™-BMD. Keywords: Trabecular bone score; FRAX™; Bone mineral density; Postmenopausal women; Osteoporosis

Assessment of Osteoporosis and Fracture Risk in Mastocytosis within a North American Cohort

Systemic mastocytosis (SM), a clonal expansion of mast cells affecting multiple organs including the skeletal system, puts patients at risk for osteoporosis and fractures. Various aspects of skeletal disease in SM have been reported among European cohorts. To determine fracture prevalence and risk predictors in SM in a North American (NA) cohort and compare findings with studies of other populations. Fifty patients, aged 25-74 years, were grouped based on fracture type and history. Data collected included laboratory findings and radiographic markers such as serum tryptase, bone turnover markers, dual-energy x-ray absorptiometry images, and trabecular bone scores. We performed univariate and multivariate analyses of these findings. Fracture history was found in 74% of patients. Significantly different median age, body mass index, dual-energy x-ray absorptiometry scores, and alkaline phosphatase levels were observed between fracture groups, consistent with French and Dutch studies. Significant findings included the difference in trabecular bone scores among fracture groups, the association between alkaline phosphatase and fracture type and occurrence, and the model for predicting fracture risk based on DXA spine T-scores, alkaline phosphatase, and age (81.3% accuracy and 77.1% sensitivity). Our findings in an NA cohort are in overall agreement with those reported in European studies of skeletal disease and fracture risk for individuals with SM. We include an interactive calculator designed from a predictive model based on the NA cohort, which may be used for improved screening for fracture risk.

Association Between DXA And HR-pQCT Measurements Of BMD In Active, Recruit-aged Men And Women

Dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD) measurements are routinely employed to assess fracture risk despite the limitations of a two-dimensional, estimated projection of bone volume. Conversely, high-resolution peripheral quantitative computed tomography (HR-pQCT) provides three-dimensional volumetric BMD (vBMD) measurements of total, trabecular, and cortical bone, offering better characterization of fracture risk. It remains unclear whether regional aBMD accurately reflects vBMD of specific bone compartments in the distal tibia, a common injury site for military personnel. PURPOSE: To determine if lower limb aBMD correlates with distal total (Tt), trabecular (Tb) and cortical (Ct) vBMD in healthy, recruit-aged men and women. METHODS: Seventy-six recreationally active men (n = 43;26.4 ± 0.8 yrs.), and women (n = 33;26.2 ± 4.7 yrs.), free of any musculoskeletal conditions that could influence BMD, completed two HR-pQCT (XtremeCT; Scanco Medical) and one total body DXA (Lunar iDXA; GE Healthcare) scans. Total body DXA and non-dominant tibial HR-pQCT scans at the metaphysis (4% site) and diaphysis (30% site) were obtained. Lower leg aBMD was assessed in DXA scans with custom region of interest (ROI) analysis between the ultradistal tibia and the tibial plateau. Associations between variables were analyzed with Pearson’s correlation coefficient (r2); alpha was set at p < 0.05. RESULTS: aBMD positively correlated with Tt vBMD at the 4% site for men (r2 = 0.42; p < 0.001) and women (r2 = 0.17; p = 0.016) but only in men at the 30% site (r2 = 0.16; p = 0.008). aBMD positively correlated with Tb vBMD at the 4% site for men (r2 = 0.35; p < 0.001) and women (r2 = 0.20; p = 0.010), but not at the 30% site for either sex. aBMD was not correlated with Ct vBMD at the 4% site for either sex but was positively correlated with Ct vBMD at the 30% site in men (r2 = 0.12; p = 0.032). CONCLUSIONS: There is poor to moderate association between lower limb aBMD and tibial vBMD at both sites, with greater association in men than in women. aBMD is unlikely to provide a suitable assessment of distal tibial bone health. aBMD and tibial vBMD should, therefore, not be used interchangeably to examine the bone response to interventions or for the prediction of fracture risk. Supported by UK Ministry of Defence (WGCC 5.5.6-Task 0107).

Repeating bone mineral density screening after 3 years does not improve fracture risk prediction

University of Missouri FP Columbia (Founding), Columbia, MO The authors declare no conflicts of interest.

Predicting Fracture Risk in Patients with Metastatic Bone Disease of the Femur: A Pictorial Review Using Three Different Techniques.

One of the key roles of an orthopedic surgeon treating metastatic bone disease (MBD) is fracture risk prediction. Current widely used impending fracture risk tools such as Mirels scoring lack specificity. Two newer methods of fracture risk prediction, CT-based structural rigidity analysis (CTRA) and finite element analysis (FEA), have each been shown to be more accurate than Mirels. This case series illustrates comparative Mirels, CTRA, and FEA for 8 femurs in 7 subjects. These cases were selected from a much larger data set to portray examples of true positives, true negatives, false positives, and false negatives as defined by CTRA relative to the fracture outcome. Case illustrations demonstrate comparative Mirels and FEA. This series illustrates the use, efficacy, and limitations of these tools. As all current tools have limitations, further work is needed in refining and developing fracture risk prediction.

Response to “Physical performance test as a predictor of fracture risk”

Response to “Physical performance test as a predictor of fracture risk”

P159 Patients with Inflammatory Bowel Disease Present with Lower Trabecular Bone Scores

Abstract Background Patients with inflammatory bowel diseases (IBD) have lower bone mineral density (BMD). However, BMD does not reflect bone micro-structure/geometry, nor indicates the intrinsic properties of bone tissue. The trabecular bone score (TBS) delivers an indirect measurement of bone microarchitecture and predicts fracture risk independent of bone density. The aim of this study was to assess if patients with IBD present with lower TBS vs a healthy control (HC) population and to identify variables associated with lower TBS. Methods This prospective cohort study included patients with active Crohn’s disease (CD) or ulcerative colitis (UC) and a matched HC group. Patients with ostomies, short gut or known endocrine co-morbidities associated with low BMD, patients with osteoporosis on pharmacologic therapy were excluded. L1-L4 TBS and BMD parameters were determined by dual-energy X-ray absorptiometry (DXA) using a GE Lunar iDXA scan and TBS iNsight™ and GE enCORE™. Other collected variables included demographics, disease phenotype, laboratories (25-OH vitamin D [25OHD] and parathyroid hormone levels [PTH]), disease activity (c-reactive protein [CRP], simple endoscopic score [SES-CD] in CD, and endoscopic Mayo score [EMS] in UC). IBD severity was stratified based on endoscopy: mild (EMS=1 in UC or SES-CD=3–6), moderate (EMS=2 or SES-CD=7–15) and severe (EMS=3 or SES-CD&amp;gt;15). The primary outcome was the L1-L4 TBS. Secondary outcomes were left total and neck femoral BMD and the L1-L4 region BMD. Results A total of 141 patients were included (115 IBD and 26 HC). Patients with IBD had significantly lower TBS, femoral and L1-L4 BMD and Z-Scores when compared to controls (Figure 1). Endoscopic disease activity was not associated with TBS (Figure 2) or total/neck femur and L1-L4 BMD and Z-scores (p&amp;gt;0.05 for all). When stratifying levels by 25OHD quartiles, patients with 25OHD ≥28 ng/mL (the highest 50th percentile of the study population) had significantly higher TBS Z-scores when compared to those with 25OHD ≤28 ng/mL (0.3 [-0.2 – 1.1] vs -0.1 [-1.1 – 0.5], p=0.002). No associations were seen between TBS Z-scores and use of steroids, gender, type of IBD (UC vs CD), smoking status or when comparing females 50 years or older vs the rest of the group (p&amp;gt;0.05 for all). Moreover, there were no differences in TBS between patients who did or did not engage in resistance exercises (p=0.22) and/or regular aerobic exercises (RAPA ≥6) (p=0.84). Conclusion Patients with IBD present with lower TBS Z-scores when compared to HC and there is no correlation with disease activity. The only variable associated with lower TBS was a 25OHD &amp;lt;28 ng/mL. Further studies looking at the implications of these findings are warranted. FIGURE 1 FIGURE 2

Predictive ability of novel volumetric and geometric indices derived from dual-energy X-ray absorptiometric images of the proximal femur for hip fracture compared with conventional areal bone mineral density: the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

To clarify whether volumetric and geometric indices derived from novel three-dimensional (3D) modeling of the hip using dual-energy X-ray absorptiometric (DXA) images improve hip fracture prediction relative to areal bone mineral density (aBMD). We examined 1331 women who had completed the baseline survey and at least one follow-up survey over 20 years (age 40-79 years at baseline). Each survey included aBMD measurement at the hip by DXA. Volumetric and geometric indices of the hip at baseline and the 10-year follow-up were estimated from DXA images using a 3D modeling algorithm. Incident hip fractures during the 20-year follow-up period were identified through self-report. Cox proportional hazards regression models allowing for repeated measurements of predictors and outcomes were constructed, and their predictive ability for hip fracture was evaluated using areas under receiver operating characteristic curves (AUCs) and net reclassification improvement (NRI) over aBMD at the femoral neck (FN) and total hip (TH) as references. During a median follow-up of 19.8 years, 68 incident hip fractures were identified (2.22/1000 person-years). A significantly larger AUC of trabecular volumetric BMD (vBMD) at the total hip (AUC = 0.741), femoral neck (AUC = 0.748), and intertrochanter (AUC = 0.738) and significant NRI (0.177, 0.149, and 0.195, respectively) were observed compared with FN-aBMD (AUC = 0.701), but not TH-aBMD. vBMD obtained from 3D modeling using routinely obtained hip DXA images significantly improved hip fracture risk prediction over conventional FN-aBMD, but not TH-aBMD. The Japanese Population-Based Osteoporosis (JPOS) Cohort Study was retrospectively registered as UMIN000032869 in the UMIN Clinical Trials Registry on July 1, 2018.

The clinical application of high-resolution peripheral computed tomography (HR-pQCT) in adults: state of the art and future directions

High-resolution peripheral computed tomography (HR-pQCT) was developed to image bone microarchitecture in vivo at peripheral skeletal sites. Since the introduction of HR-pQCT in 2005, clinical research to gain insight into pathophysiology of skeletal fragility and to improve prediction of fractures has grown. Meanwhile, the second-generation HR-pQCT device has been introduced, allowing novel applications such as hand joint imaging, assessment of subchondral bone and cartilage thickness in the knee, and distal radius fracture healing. This article provides an overview of the current clinical applications and guidance on interpretation of results, as well as future directions. Specifically, we provide an overview of (1) the differences and reference data for HR-pQCT variables by age, sex, and race/ethnicity; (2) fracture risk prediction using HR-pQCT; (3) the ability to monitor response of anti-osteoporosis therapy with HR-pQCT; (4) the use of HR-pQCT in patients with metabolic bone disorders and diseases leading to secondary osteoporosis; and (5) novel applications of HR-pQCT imaging. Finally, we summarize the status of the application of HR-pQCT in clinical practice and discuss future directions. From the clinical perspective, there are both challenges and opportunities for more widespread use of HR-pQCT. Assessment of bone microarchitecture by HR-pQCT improves fracture prediction in mostly normal or osteopenic elderly subjects beyond DXA of the hip, but the added value is marginal. The prospects of HR-pQCT in clinical practice need further study with respect to medication effects, metabolic bone disorders, rare bone diseases, and other applications such as hand joint imaging and fracture healing. The mostly unexplored potential may be the differentiation of patients with only moderately low BMD but severe microstructural deterioration, which would have important implications for the decision on therapeutical interventions.

POS0163 INCIDENT FRACTURE RISK PREDICTION USING THE FRAGILITY SCORE CALCULATED BY LUMBAR SPINE RADIOFREQUENCY ECHOGRAPHIC MULTI SPECTROMETRY (REMS) SCANS

Background:The main consequence of osteoporosis is the occurrence of fractures due to bone fragility, with important sequelae in terms of disability and mortality. It has been already demonstrated that the information about bone mass density (BMD) alone is not sufficient to predict the risk of fragility fractures, since several fractures occur in patients with normal BMD [1].The Fragility Score is a parameter that allows to estimate skeletal fragility thanks to a trans-abdominal ultrasound scan performed with Radiofrequency Echographic Multi Spectrometry (REMS) technology. It is calculated by comparing the results of the spectral analysis of the patient’s raw ultrasound signals with reference models representative of fragile and non-fragile bones [2]. It is a dimensionless parameter, which can vary from 0 to 100, in proportion to the degree of fragility, independently from BMD.Objectives:This study aims to evaluate the effectiveness of Fragility Score, measured during a bone densitometry exam performed with REMS technology at lumbar spine, in identifying patients at risk of incident osteoporotic fractures at a follow-up period of 5 years.Methods:Caucasian women with age between 30 and 90 were scanned with spinal REMS and DXA. The incidence of osteoporotic fractures was assessed during a follow-up period of 5 years. The ability of the Fragility Score to discriminate between patients with and without incident fragility fractures was subsequently evaluated and compared with the discriminatory ability of the T-score calculated with DXA and with REMS.Results:Overall, 533 women (median age: 60 years; interquartile range [IQR]: 54-66 years) completed the follow-up (median 42 months; IQR: 35-56 months), during which 73 patients had sustained an incident fracture.Both median REMS and DXA measured T-score values were significantly lower in fractured patients than for non-fractured ones, conversely, REMS Fragility Score was significantly higher (Table 1).Table 1.Analysis of T-score values calculated with REMS and DXA and Fragility Score calculated with REMS. Median values and interquartile ranges (IQR) are reported. The p-value is derived from the Mann-Whitney test.Patients without incident fragility fracturePatients with incident fragility fracturep-valueT-score DXA[median (IQR)]-1.9 (-2.7 to -1.0)-2.6 (-3.3 to -1.7)0.0001T-score REMS[median (IQR)]-2.0 (-2.8 to -1.1)-2.7 (-3.5 to -1.9)&lt;0.0001Fragility Score[median (IQR)]29.9 (25.7 to 36.2)53.0 (34.2 to 62.5)&lt;0.0001By evaluating the capability to discriminate patients with/without fragility fractures, the Fragility Score obtained a value of the ROC area under the curve (AUC) of 0.80, higher than the AUC of the REMS T-score (0.66) and of the T-score DXA (0.64), and the difference was statistically significant (Figure 1).Figure 1.ROC curve comparison of Fragility Score, REMS and DXA T-score values in the classification of patients with incident fragility fractures.Furthermore, the correlation between the Fragility Score and the T-score values was low, with Pearson correlation coefficient r=-0.19 between Fragility Score and DXA T-score and -0.18 between the Fragility Score and the REMS T-score.Conclusion:The Fragility Score was found to be an effective tool for the prediction of fracture risk in a population of Caucasian women, with performances superior to those of the T-score values. Therefore, this tool presents a high potential as an effective diagnostic tool for the early identification and subsequent early treatment of bone fragility.