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Development of an adjustment factor of the ten year probability of fracture (FRAX®) based on an independent bone texture parameter (Trabecular Bone Score) to enhance the detection of patient at risk of fracture: The FRAXOS study

English title Development of an adjustment factor of the ten year probability of fracture (FRAX®) based on an independent bone texture parameter (Trabecular Bone Score) to enhance the detection of patient at risk of fracture: The FRAXOS study
Applicant Didier Hans
Number 156978
Funding scheme Project funding (special)
Research institution Département de l'Appareil Locomoteur - DAL Centre Hospital Universitaire Vaudois - CHUV
Institution of higher education University of Lausanne - LA
Main discipline Methods of Epidemiology and Preventive Medicine
Start/End 01.11.2014 - 31.10.2018
Approved amount 454'000.00
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All Disciplines (4)

Discipline
Methods of Epidemiology and Preventive Medicine
Diseases of Bones and Joints
Geriatrics
Medical Statistics

Keywords (6)

FRAX; Fracture prediction; Bone microarchitecture; Bone Texture; Osteoporosis; large nested project (Psy-CoLaus)

Lay Summary (French)

Lead
L’ostéoporose est un problème majeur de santé publique dont les fractures touchent 1 femme sur deux après 50 ans. Il existe des outils diagnostiques et des protocoles de prise en charges de ces patients bien établis mais les résultats restent insuffisants. Cependant l’intégration des nouveautés technologiques dans les outils existant pourrait permettre d’avoir une vision plus complète de l’état du patient et devrait ainsi permettre une meilleure estimation du risque de fracture afin de mieux cibler les interventions en termes de prévention et de traitement. Le projet a donc pour but d’améliorer de manière significative les performances cliniques de nos outils actuels
Lay summary

Introduction

L’ostéoporose est un problème majeur de santé publique dont les fractures touchent 50% des femmes après 50 ans. Disposer d’un outil performant pour évaluer le risque fracturaire est déterminant pour proposer un traitement aux femmes qui en ont le plus besoin.

Objectifs du travail de recherche

L’ostéoporose est définie par une diminution de la densité osseuse (DO) et une altération de la microarchitecture. Cependant 50% des fractures ostéoporotiques apparaissent chez des femmes sans ostéoporose densitométrique. FRAXÒ est l’outil le mieux validé pour prédire le risque de fracture, mais sa performance est modeste. Il combine DO et facteurs de risque clinique. Le trabecular bone score (TBS) est facile à obtenir par une simple ré-analyse informatique de l’image de DO lombaire. Il est corrélé à la microarchitecture osseuse et donne des informations importantes pour la clinique indépendantes de la DO. Si le TBS est capable de donner des informations non capturées par la DO, il pourrait être utilisé dans un algorithme permettant une meilleure prédiction du risque de fracture.

Le but de ce projet est d’améliorer la prédiction du risque de fracture en développant et validant un modèle FRAXÒ qui incorpore le TBS. Les données de plus de 45000 femmes issues de cohortes suisses et internationales seront utilisées pour développer (une cohorte principale) et valider le modèle (méta-analyse des autres).

Contexte scientifique et social du projet

Le TBS est une technique innovante et facile à mesurer. Ce projet devrait permettre une meilleure estimation du risque de fracture afin de mieux cibler les interventions en termes de prévention et de traitement. Ceci est important au vu du vieillissement de la population et du coût lié à la prise en charge des fractures ostéoporotiques.

Direct link to Lay Summary Last update: 24.11.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Review on the Utility of Trabecular Bone Score, a Surrogate of Bone Micro-architecture, in the Chronic Kidney Disease Spectrum and in Kidney Transplant Recipients
Shevroja Enisa, Lamy Olivier, Hans Didier (2018), Review on the Utility of Trabecular Bone Score, a Surrogate of Bone Micro-architecture, in the Chronic Kidney Disease Spectrum and in Kidney Transplant Recipients, in Frontiers in Endocrinology, 9, 1-6.
Menopausal Hormone Therapy Is Associated With Reduced Total and Visceral Adiposity: The OsteoLaus Cohort
Papadakis Georgios E, Hans Didier, Rodriguez Elena Gonzalez, Vollenweider Peter, Waeber Gerard, Marques-Vidal Pedro, Lamy Olivier (2018), Menopausal Hormone Therapy Is Associated With Reduced Total and Visceral Adiposity: The OsteoLaus Cohort, in The Journal of Clinical Endocrinology & Metabolism, 103(5), 1948-1957.
Cohort Profile: The OsteoLaus Study, design and cohort overview through the second follow-up visit
shevrojaEnisa, Marques-VidalPedro, Aubry-RozierBerengere, HansGabriel, RivadeneiraFermando, LamyOlivier, HansDidier (2018), Cohort Profile: The OsteoLaus Study, design and cohort overview through the second follow-up visit, in International Journal Of Epidemiology, 1-9.
High Evening Cortisol Level Is Associated With Low TBS and Increased Prevalent Vertebral Fractures: OsteoLaus Study
Gonzalez Rodriguez Elena, Lamy Olivier, Stoll Delphine, Metzger Marie, Preisig Martin, Kuehner Christine, Vollenweider Peter, Marques-Vidal Pedro, Waeber Gérard, Aubry-Rozier Bérengère, Hans Didier (2017), High Evening Cortisol Level Is Associated With Low TBS and Increased Prevalent Vertebral Fractures: OsteoLaus Study, in The Journal of Clinical Endocrinology & Metabolism, 102(7), 2628-2636.
Use of Trabecular Bone Score (TBS) as a Complementary Approach to Dual-energy X-ray Absorptiometry (DXA) for Fracture Risk Assessment in Clinical Practice
Shevroja Enisa, Lamy Olivier, Kohlmeier Lynn, Koromani Fjorda, Rivadeneira Fernando, Hans Didier (2017), Use of Trabecular Bone Score (TBS) as a Complementary Approach to Dual-energy X-ray Absorptiometry (DXA) for Fracture Risk Assessment in Clinical Practice, in Journal of Clinical Densitometry, 20(3), 334-345.
The lumbar spine age-related degenerative disease influences the BMD not the TBS: the Osteolaus cohort
Padlina I., Gonzalez-Rodriguez E., Hans D., Metzger M., Stoll D., Aubry-Rozier B., Lamy O. (2017), The lumbar spine age-related degenerative disease influences the BMD not the TBS: the Osteolaus cohort, in Osteoporosis International, 28(3), 909-915.
The Benefit of Menopausal Hormone Therapy on Bone Density and Microarchitecture Persists After its Withdrawal
Papadakis Georgios, Hans Didier, Gonzalez-Rodriguez Elena, Vollenweider Peter, Waeber Gérard, Marques-Vidal Pedro Manuel, Lamy Olivier (2016), The Benefit of Menopausal Hormone Therapy on Bone Density and Microarchitecture Persists After its Withdrawal, in The Journal of Clinical Endocrinology & Metabolism, 101(12), 5004-5011.
Reproducibility of Vertebral Fracture Assessment Readings From Dual-energy X-ray Absorptiometry in Both a Population-based and Clinical Cohort: Cohen's and Uniform Kappa
Aubry-Rozier Bérengère, Chapurlat Roland, Duboeuf François, Iglesias Katia, Krieg Marc-Antoine, Lamy Olivier, Burnand Bernard, Hans Didier (2015), Reproducibility of Vertebral Fracture Assessment Readings From Dual-energy X-ray Absorptiometry in Both a Population-based and Clinical Cohort: Cohen's and Uniform Kappa, in Journal of Clinical Densitometry, 18(2), 233-238.

Collaboration

Group / person Country
Types of collaboration
Winnipeg University Canada (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Sheffield University Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Erasmus MC - University Medical Center , Departments of Internal Medicine and Epidemiology Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Lyon University Hospital / INSERM - Lyon France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
American Society of Bone and Mineral Research (ASBMR) Poster The Impact of a Beta Trabecular Bone Score (TBS) Algorithm Accounting for Soft Tissue Thickness Correction on the Prediction of Incident Major Osteoporotic Fracture (MOF) Risk in Postmenopausal Women: The OsteoLaus Study 28.09.2018 Montreal, Canada Didier Hans; Shevroja Enisa;
European Calcified Tissue Society Poster Impact of the new trabecular bone score (TBS) algorithm using a different correction model based on soft tissue thickness on the prediction of incident atraumatic fracture risk in elderly women: The OsteoLaus prospective Study 26.05.2018 Valencia, Spain Didier Hans; Shevroja Enisa;
World Conference for Osteoporosis Poster The prediction of incident atraumatic fracture risk by trabecular bone score (TBS) correction algorithms in elderly women of the OsteoLaus Study 19.04.2018 Krakow, Poland Lamy Olivier; Shevroja Enisa; Didier Hans;
International Society of Clinical Densitometry (ISCD) Talk given at a conference The utility of TBS-adjusted BMD T-score in the discrimination of the major osteoporotic fractures in the postmenopausal women of the Rotterdam and the Osteolaus Studies 28.02.2018 Boston, United States of America Didier Hans; Shevroja Enisa;
American Society of Bone and Mineral Research (ASBMR) Poster The validity of the TBS-adjusted BMD T-score in fracture risk prediction: The OsteoLaus and Rotterdam Studies 09.09.2017 Denver, United States of America Didier Hans; Shevroja Enisa;
European Calcified Tissue Society (ECTS) Talk given at a conference Prediction of incident atraumatic fracture risk by TBS in the elderly women of the OsteoLaus Study 12.05.2017 Salzburg, Austria Shevroja Enisa; Didier Hans;
Annual conference of the International Society of Clinical Densitometry (ISCD) Talk given at a conference Prediction of incident atraumatic fracture risk by TBS in the elderly women of the OsteoLaus Study 20.04.2017 Orlando, United States of America Didier Hans; Shevroja Enisa;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Annual Research Meeting of the Department of Internal Medicine, Erasmus Medical Center Talk 12.01.2017 Rotterdam, Netherlands Shevroja Enisa;


Awards

Title Year
ISCD Young Investigator Award 2018
ASBMR Young Investigator Travel Grant 2017
ISCD Best Clinician Abstract 2017

Associated projects

Number Title Start Funding scheme
188886 Towards semi-personalized (cluster) medicine with the optimal osteoporotic fracture prediction: artificial intelligence- or current human- based models? The OsteoLaus Project 01.10.2019 Project funding (Div. I-III)
173092 Longitudinal metabolome- and genome-wide assessment of the CoLaus population to develop predictive signatures for early detection of type 2 diabetes 01.09.2017 Project funding (Div. I-III)
122661 Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study 01.01.2009 Cohort Studies Large

Abstract

Osteoporosis is a major public health issue and is expected to become even more important in the next decades with population aging. Clinical consequences of osteoporosis are fragility fractures (mainly vertebral), wrist, humerus and hip fractures. Hip fractures are the most serious, and are responsible for a significant increase in death and institutionalization. Vertebral fractures can be disabling and also increase mortality. Prior to a fragility fracture, the definition of osteoporosis is based on bone mineral density (BMD).Fracture risk assessment is crucial to identify subjects at high risk of fracture for whom treatment is most appropriate, and to avoid unnecessary treatment for subjects at low risk. Several effective pharmacological treatments have been shown to prevent osteoporotic fractures in clinical trials. However, many individuals that might benefit from treatment are not identified before a major fracture occurs.The rationale to improve fracture prediction is the modest performance of existing prediction scores. Indeed, inclusion of risk factors in the FRAX® model (FRAX: Fracture Risk Assessment tool) was predicated on their ability to predict fractures, independently of each other and independently of BMD, and to indirectly capture some aspects of bone quality. Studies using texture analysis of human cadaver vertebrae have suggested that trabecular bone score (TBS) is an interesting marker of changes in bone micro-architecture and captures clinically relevant information on skeletal changes independent of BMD. If TBS is able to provide a direct assessment of how some of these non-BMD risk factors affect fracture risk, then it could effectively replace one or more of these risk factors in future fracture risk algorithms. Alternatively, the TBS could be used as a covariate in the current FRAX model to improve fracture prediction.Thus, the objective of this project is to assess the importance of bone micro-architectural estimation in improving the current FRAX model by developing and validating a FRAX model including estimates of bone micro-architecture. The project will use already available data from Swiss and international cohorts representing over 45000 subjects (the largest cohort will be used to develop the model and the sum of the others cohorts will be used for validation).If successful, this work will lead to better fracture risk estimation and classification, which will improve targeting of interventions to prevent fragility fractures. Given the ageing of the population and the expected increase in osteoporotic fractures, the health and economic benefits of an improved risk estimator would be considerable. A clinical tool (such as online calculator or risk tables) will be developed for physicians to calculate fracture prediction, thus facilitating individual treatment. This project will enable a strong interdisciplinary collaboration between doctors, physicists, and statisticians directed towards a major public health problem.
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