Hepatic osteodystrophy and fracture risk prediction using FRAX tool in Indian patients with cirrhosis.
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SUBMITTER: De A
PROVIDER: S-EPMC7578334 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Hepatic osteodystrophy and fracture risk prediction using FRAX tool in Indian patients with cirrhosis.
De Arka A Ray Debadrita D Lamoria Sandeep S Sharma Vishal V Khurana Tilak Raj TR
JGH open : an open access journal of gastroenterology and hepatology 20200612 5
<h4>Background and aim</h4>The main clinical relevance of hepatic osteodystrophy is the increased risk of fractures. Dual-energy X ray absorptiometry (DEXA)-based assessment of bone mineral density, the current gold standard for diagnosing osteoporosis, is not the sole determinant of fracture risk. Other clinical risk factors also play an important role. This study was carried out to assess the prevalence and risk factors of hepatic osteodystrophy and estimate the entailed fracture risk by using ...[more]
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Project description:A frailty index (FI) of deficit accumulation could quantify and predict the risk of fractures based on the degree of frailty in the elderly. We aimed to compare the predictive powers between the FI and the fracture risk assessment tool (FRAX) in predicting risk of major osteoporotic fracture (hip, upper arm or shoulder, spine, or wrist) and hip fracture, using the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort. There were 3985 women included in the study, with the mean age of 69.4 years (standard deviation [SD] = 8.89). During the follow-up, there were 149 (3.98%) incident major osteoporotic fractures and 18 (0.48%) hip fractures reported. The FRAX and FI were significantly related to each other. Both FRAX and FI significantly predicted risk of major osteoporotic fracture, with a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 1.02-1.05) and 1.02 (95% CI: 1.01-1.04) for per-0.01 increment for the FRAX and FI respectively. The HRs were 1.37 (95% CI: 1.19-1.58) and 1.26 (95% CI: 1.12-1.42) for an increase of per-0.10 (approximately one SD) in the FRAX and FI respectively. Similar discriminative ability of the models was found: c-index = 0.62 for the FRAX and c-index = 0.61 for the FI. When cut-points were chosen to trichotomize participants into low-risk, medium-risk and high-risk groups, a significant increase in fracture risk was found in the high-risk group (HR = 2.04, 95% CI: 1.36-3.07) but not in the medium-risk group (HR = 1.23, 95% CI: 0.82-1.84) compared with the low-risk women for the FI, while for FRAX the medium-risk (HR = 2.00, 95% CI: 1.09-3.68) and high-risk groups (HR = 2.61, 95% CI: 1.48-4.58) predicted risk of major osteoporotic fracture significantly only when survival time exceeded 18months (550 days). Similar findings were observed for hip fracture and in sensitivity analyses. In conclusion, the FI is comparable with FRAX in the prediction of risk of future fractures, indicating that measures of frailty status may aid in fracture risk assessment and fracture prevention in the elderly. Further evidence from randomized controlled trials of osteoporosis medication interventions is needed to support the FI and FRAX as validated measures of fracture risk.
| S-EPMC5104554 | biostudies-literature
Project description:The Fracture Risk Assessment Tool (FRAX) is the most widely used tool for fracture prediction. It provides 10-year probabilities for hip and major osteoporotic fracture (MOF). It uses country-specific hip fracture incidence and life expectancy data, and for most countries, MOF/hip fracture incidence rate ratios (IRRs) from Malmo Sweden. However, the risk of MOF varies by age, sex, and geography. The objective is to compare the MOF/hip IRRs across countries, by sex and age. This systematic review targeted observational studies of MOF and hip fractures in individuals >50 years (PROSPERO 2019 CRD42019129259). One reviewer screened potential articles. Two reviewers completed duplicate and independent data abstraction, and assessed study quality based on population representativeness, study design and duration, definition of ethnicity, and fracture characteristics. We calculated the MOF/hip IRRs (95% confidence interval) and Z-values to compare IRRs in various countries to those for Sweden. We included 27 studies, of fair to good quality in the majority, from Europe (15), US and Canada (7), Asia (3), and Australia (2). The IRRs were twofold to 10-fold higher in younger compared to older age categories, and in women compared to men, with few exceptions. Within Europe, and using Sweden as a reference, MOF/Hip IRRs in women 50-54 years from Finland, Italy, Netherlands, Denmark, and UK were significantly lower by 38% to 60%. Findings were similar in men. At older ages, MOF/Hip IRRs were consistently lower in women from European countries compared to Sweden, by 10%-40% and 11%-51%, at 75-79 years and 85-89 years, respectively. Findings were heterogenous in men and in non-European countries. In conclusion, the MOF/hip fracture IRR may vary between countries. The variability at older ages may affect FRAX prediction when country-specific fracture IRRs are not used. Further research is needed to elucidate the implication of our findings to FRAX-derived MOF estimates in various countries. © 2021 American Society for Bone and Mineral Research (ASBMR).
| S-EPMC8531513 | biostudies-literature
Project description:UNLABELLED: The present study estimated the 10-year probability using the Japanese version of WHO fracture risk assessment tool (FRAX) in order to determine fracture probabilities that correspond to intervention thresholds currently used in Japan and to resolve some issues for its use in Japan. INTRODUCTION: The objective of the present study was to evaluate a Japanese version of the WHO fracture risk assessment (FRAX) tool to compute 10-year probabilities of osteoporotic fracture in Japanese men and women. Since lumbar spine bone mineral density (BMD) is used preferentially as a site for assessment, and densitometers use Japanese reference data, a second aim was to investigate the suitability and impact of this practice in Japan. METHODS: Fracture probabilities were computed from published data on the fracture and death hazards in Japan. Probabilities took account of age, sex, the presence of clinical risk factors and femoral neck BMD. Fracture probabilities were determined that were equivalent to intervention thresholds currently used in Japan. The difference between T-scores derived from international reference data and that using Japanese-specific normal ranges was estimated from published sources. The gradient of risk of BMD for fracture in Japan was compared to that for BMD at the lumbar spine in the Hiroshima cohort. RESULTS: The 10-year probabilities of a major osteoporosis-related fracture that corresponded to current intervention thresholds ranged from approximately 5% at the age of 50 years to more than 20% at the age of 80 years. The use of femoral neck BMD predicts fracture as well as or better than BMD tests at the lumbar spine. There were small differences in T-scores between those used for the model and those derived from a Japanese reference population. CONCLUSIONS: The FRAX mark tool has been used to determine possible thresholds for therapeutic intervention, based on equivalence of risk with current guidelines. The approach will need to be supported by appropriate health economic analyses. Femoral neck BMD is suitable for the prediction of fracture risk among Japanese. However, when applying the FRAX model to Japan, T-scores and Z-scores should be converted to those derived from the international reference.
| S-EPMC2267486 | biostudies-other
Project description:BackgroundAge-related bone loss is asymptomatic, and the morbidity of osteoporosis is secondary to the fractures that occur. Common sites of fracture include the spine, hip, forearm and proximal humerus. Fractures at the hip incur the greatest morbidity and mortality and give rise to the highest direct costs for health services. Their incidence increases exponentially with age.Independently changes in population demography, the age - and sex- specific incidence of osteoporotic fractures appears to be increasing in developing and developed countries. This could mean more than double the expected burden of osteoporotic fractures in the next 50 years.Methods/designTo assess the predictive power of the WHO FRAX™ tool to identify the subjects with the highest absolute risk of fragility fracture at 10 years in a Spanish population, a predictive validation study of the tool will be carried out. For this purpose, the participants recruited by 1999 will be assessed. These were referred to scan-DXA Department from primary healthcare centres, non hospital and hospital consultations.Study populationPatients attended in the national health services integrated into a FRIDEX cohort with at least one Dual-energy X-ray absorptiometry (DXA) measurement and one extensive questionnaire related to fracture risk factors.MeasurementsAt baseline bone mineral density measurement using DXA, clinical fracture risk factors questionnaire, dietary calcium intake assessment, history of previous fractures, and related drugs. Follow up by telephone interview to know fragility fractures in the 10 years with verification in electronic medical records and also to know the number of falls in the last year. The absolute risk of fracture will be estimated using the FRAX™ tool from the official web site.DiscussionSince more than 10 years ago numerous publications have recognised the importance of other risk factors for new osteoporotic fractures in addition to low BMD. The extension of a method for calculating the risk (probability) of fractures using the FRAX™ tool is foreseeable in Spain and this would justify a study such as this to allow the necessary adjustments in calibration of the parameters included in the logarithmic formula constituted by FRAX™.
| S-EPMC3224379 | biostudies-literature
Project description:Bone loss is common in advanced cirrhosis, although the precise mechanisms underlying bone loss in cirrhosis are unknown. We studied the profile and functionality of bone-forming cells and bone-building proteins in bone marrow (BM) of individuals with cirrhosis (n = 61) and individuals without cirrhosis as normal controls (n = 50). We also performed dual energy X-ray absorptiometry for clinical correlation. BM mesenchymal cells (MSCs) were analyzed for colony-forming units-fibroblasts and their osteogenic (fibronectin-1 [FN1], insulin-like growth factor binding protein 3 [IGFBP3], collagen type 1 alpha 1 chain [COL1A1], runt-related transcription factor 2 [RUNX2], and alkaline phosphatase, liver [ALPL]) and adipogenic ( adiponectin, C1Q, and collagen domain containing [ADIPOQ], peroxisome proliferator-activated receptor gamma [PPARγ], and fatty acid binding protein 4 [FABP4]) potentials. Colony-forming units-fibroblasts were lower in patients with cirrhosis (P = 0.002) than in controls. Cirrhotic BM-MSCs showed >2-fold decrease in osteogenic markers. Compared to controls, patients with cirrhosis showed fewer osteocytes (P = 0.05), osteoblasts, chondroblasts, osteocalcin-positive (osteocalcin+) area, clusters of differentiation (CD)169+ macrophages (P < 0.001, each), and nestin+ MSCs (P = 0.001); this was more apparent in Child-Turcotte-Pugh (CTP) class C than A (P < 0.001). Multivariate logistic regression showed low nestin+ MSCs (P = 0.004) as a predictor of bone loss. Bone-resolving osteoclasts were comparable among CTP groups, but >2-fold decreased anti-osteoclastic and increased pro-osteoclastic factors were noted in patients with CTP C compared to CTP A. Bone-building proteins (osteocalcin [P = 0.008], osteonectin [P < 0.001], and bone morphogenic protein 2 [P = 0.001]) were decreased while anti-bone repair factors (fibroblast growth factor 23 [P = 0.015] and dipeptidyl peptidase 4 [P < 0.001]) were increased in BM and peripheral blood; this was more apparent in advanced cirrhosis. The dual energy X-ray absorptiometry scan T score significantly correlated with the population of osteoblasts, osteocytes, MSCs, and CD169+ macrophages. Conclusion: Osteoprogenitor cells are substantially reduced in patients with cirrhosis and more so in advanced disease. Additionally, increased anti-bone repair proteins enhance the ineffective bone repair and development of osteoporosis in cirrhosis. Hepatology Communications 2018;0:0-0).
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Project description: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.
| S-EPMC8169615 | biostudies-literature
Project description:We identified large between-ethnicity calibration differences in the Canadian FRAX® tool which substantially overestimated the major osteoporotic fracture (MOF) risk in Asian women and Black women, and overestimated hip fracture risk in Asian women.PurposeFRAX® is calibrated using population-specific fracture and mortality data. The need for FRAX to accommodate ethnic diversity within a country is uncertain. We addressed this question using the population-based Manitoba Bone Mineral Density (BMD) Program registry and self-reported ethnicity.MethodsThe study population was women aged 40 years or older with baseline FRAX assessments (Canadian and other ethnic calculators), fracture outcomes, and self-reported ethnicity (White N = 68,907 [referent], Asian N = 1910, Black N = 356). Adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to MOF and hip fracture were estimated. We examined candidate variables from DXA that might contribute to ethnic differences including skeletal size, hip axis length (HAL), trabecular bone score (TBS), and estimated body composition.ResultsAdjusted for baseline risk using the Canadian FRAX tool with BMD, Asian women compared with White women were at much lower risk for MOF (HR 0.46, 95% CI 0.35-0.59) and hip fracture (0.16, 95% CI 0.08-0.34). Black women were also at lower MOF risk (HR 0.58, 95% CI 0.32-1.00); there were no hip fractures. The US ethnic-specific FRAX calculators accounted for most of the between-ethnicity differences in MOF risk (86% for Asian, 92% for Black) but only partially accounted for lower hip fracture risk in Asian women (40%). The candidate variables explained only a minority of the effect of ethnicity. Gradient of risk in analyses was similar (p-interactions ethnicity*FRAX non-significant).ConclusionsWe identified significant ethnic differences in performance of the Canadian FRAX tool with fracture probability overestimated among Asian and Black women. The US ethnic calculators helped to address this discrepancy for MOF risk assessment, but not for hip fracture risk among Asian women.
| S-EPMC7611612 | biostudies-literature
Project description:FRAX is a validated, computer-based clinical fracture risk calculator that estimates the 10-year risk of major osteoporotic (clinical spine, forearm, hip, or shoulder) fracture, and hip fracture alone. It is widely used for decision making in fracture prevention, but it may underestimate the risk in HIV-infected individuals. Some experts recommend considering HIV as a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals.From the Veterans Aging Cohort Study Virtual Cohort, we included 24,451 HIV-infected and uninfected men aged 50-70 years with complete data in the year 2000 to approximate all but 2 factors (ie, history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10-year observational data for incident fragility fracture. The accuracy of the modified-FRAX calculation was compared by the observed/estimated (O/E) ratios of fracture by HIV status.The accuracy of modified-FRAX was less for HIV-infected [O/E = 1.62, 95% confidence interval (CI) 1.45 to 1.81] than uninfected men (O/E = 1.29, 95% CI: 1.19 to 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E = 1.20, 95% CI: 1.08 to 1.34). However, only 3%-6% of men with incident fractures were correctly identified by the modified-FRAX using accepted FRAX thresholds for pharmacologic therapy.Modified-FRAX underestimated the fracture rates more in older HIV-infected than in otherwise similar uninfected men. The accuracy improved when HIV was included as a cause of secondary osteoporosis, but it still performed poorly for case finding. Further studies are necessary to determine how to use FRAX or define an HIV-specific index to risk stratify for screening and treatment in older HIV-infected individuals.
| S-EPMC4942335 | biostudies-other
Project description:Background/aimHormonal changes and hepatic osteodystrophy are less often studied complications of cirrhosis. This study describes the variance in hormones and osteodystrophy between Frail and Not frail patients with cirrhosis.Methods116 outpatients with cirrhosis were prospectively enrolled in this study. Frailty assessment was done using Liver Frailty Index (LFI). Sociodemographic assessment, anthropometry, nutritional assessment, hormone profile, and dual-energy X-ray absorptiometry scan were done in all patients.Results116 patients, predominantly males (100 (86.2%) with mean age of 50.16 years (95% CI, 48.43-51.89) were included. Malnutrition was more common in Frail group as compared to Not frail group. Subjective global assessment (SGA) class-B patients were significantly more in Frail group (37 (74%) vs 3 (4.5%), P = 0.001). The prevalence of lower parathyroid hormone (PTH) (14 (28%) vs 2 (3%)), testosterone (33 (66%) vs 15 (22.7%)), vitamin D3 (44 (88%) vs 39 (59.1%)), and cortisol (37 (74%) vs 37 (56.1) levels was higher in Frail group (P < 0.05). The number of patients diagnosed with osteodystrophy (34 (68%) vs 21 (31.8%), P = 0.001) was significantly higher in Frail group. The marker of osteoclastic activity, β-cross laps, was significantly elevated in the Frail group both in males (736 (655-818) vs 380 (329-432), P = 0.001) and (females 619 (479-758) vs 313 (83-543), P = 0.02). Bone mineral density (BMD) at lumbar spine (LS) and neck of femur (NF) had significant correlation with LFI (ρ = 0.60, P = 0.001 for LS and ρ = 0.59, P = 0.001 for NF), serum testosterone (ρ = 0.58, P = 0.001 for LS and ρ = 0.53, P = 0.001 for NF), β-cross laps (ρ = 0.38, P = 0.001for LS and ρ = 0.35, P = 0.000 for NF), vitamin D3 (ρ = 0.23, P = 0.04 for LS and ρ = 0.25, P = 0.01 for NF), PTH (ρ = 0.52, P = 0.001 for LS and ρ = 0.48. P = 0.001 for NF), and cortisol (ρ = 0.50, P = 0.001 for LS and ρ = 0.45, P = 0.001 for NF) levels.ConclusionThis is the first study that highlights the high prevalence of hormonal changes and hepatic osteodystrophy in frail patients with cirrhosis and opens a new dimension for research and target of therapy in this field.
| S-EPMC9168697 | biostudies-literature
Project description:Currently identification, and therefore, management of patients at risk of osteoporotic fracture in the UK is suboptimal. As the majority of patients who fracture have fallen, it follows that people who fall can usefully be targeted in any programme that aims to reduce osteoporotic fracture. Targeting vulnerable patients who are likely to benefit from intervention may help shift the management of fracture prevention into primary care, away from emergency departments. Paramedics who attend to patients who have fallen may be well placed to assess future fracture risk, using the Fracture Risk Assessment Tool (FRAX) and communicate that information directly to general practitioners (GPs).This feasibility study takes the form of a pragmatic, randomised controlled trial aimed at exploring and refining issues of study design, recruitment, retention, sample size and acceptability preceding a large-scale study with fracture as the end point. Patients (aged >50) who fall, call an ambulance, are attended by a study paramedic and give verbal consent will be asked FRAX and fall questions. Patients who subsequently formally consent to participation will be randomised to control (usual care) or intervention groups. Intervention will constitute transmission of calculated future fracture risk to the patients' GP with suitable, evidence-based recommendations for investigation or treatment. 3 months after the index fall, data (proportion of patients in each group undergoing investigation or starting new treatment, quality of life and health economic) will be collected and analysed using descriptive statistics. A nested qualitative study will explore issues of acceptability and study design with patients, paramedics and GPs.This protocol was approved by NRES Committee South Central Oxford C in October 2012. Research Ethics Committee ref.12/SC/0604. The study findings will be disseminated through peer-reviewed journals, conference presentations and local public events. A publication plan and authorship criteria have been preagreed.36245726.
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