Clinical assessment of bone strength

Equipe DBMS

Clinical assessment of bone strength from ultrasonic guided waves measured in axial transmission

Project duration : 3 years

Starting March 2014


  • Dr. Emmanuel Bossy, Institut Langevin, Paris, France
  • Prof. Christian Roux, INSERM, U 1153, Rheumatology Department, Cochin Hospital, Paris Descartes University, Paris, France

logo FRMWe aim at developing new ultrasound-based biomarkers of cortical bone to enhance fracture risk prediction in osteoporosis. Our approach is based on the original concept of measuring ultrasonic guided waves to yield estimates of strength-related structural and material properties of cortical bone. The project includes bio-engineering and instrumentation aspects developed by the principal applicant’s group, supported by both basic (Dr Emmanuel Bossy, Institut Langevin) and clinical research (Professeur Christian Roux, Inserm U 1153).

The main steps are:

  • Modeling wave propagation in cortical bone
    Validation of the biomarkers using multi-modal ex vivo experiments.
    A clinical study in which the performance of the biomarkers will be assessed.
A. Introduction

Osteoporosis is a medical threat with a consequent increase in bone fragility and susceptibility to fracture. There is an increasing awareness about osteoporosis, because of the consequences of fractures on morbidity, quality of life and mortality [1-3].

Fracture risk can be estimated in vivo by bone mineral density (BMD), measured by dual-energy-X-ray-absorptiometry (DXA). However, BMD does not identify all individuals at risk. Half of elderly women who present with non vertebral fractures would not be classified as osteoporotic from DXA. This lack of correlation between BMD and fractures opens the possibility that other factors, the so-called bone ‘quality factors’, including microstructure and material properties, affect bone propensity to fracture.

Such observations have triggered studies for alternative diagnostic modalities showing capacity to reach a quantitative assessment of bone quality beyond BMD. Among others, quantitative ultrasound (QUS) techniques, based on their potential to probe bone quality [4], have been proposed as an alternative to DXA.
Bone assessment has long been focused on trabecular bone, neglecting cortical bone. The role of cortical bone has recently been recognized as central to the occurrence of fractures after the age of 65 [5]. In addition, 80% of fragility fractures affect cortical bone. These results suggest that risk assessment should include accurate evaluation of cortical bone and motivate one important aspect of research in this project which is to focus measurements on cortical bone. QUS techniques are all the more relevant that the intra-cortical porosity-related bone loss is poorly captured by X-ray densitometry or CT techniques.
It has been recently evidenced that cortical bone behaves as a guide for US waves, in a similar way to optical fibers for electromagnetic waves and stethoscopes for acoustic waves. In the appropriate frequency range, cortical bone is a multi-modal waveguide (WG), which means that different modes coexist in the same WG. Our project aims at measuring guided waves in cortical bone and to infer from it bone quality factors such as cortical thickness, elasticity and porosity.

B. Research project

Specific aims

  • Modeling guided wave propagation in cortical bone. The simulations, coupled to realistic 3-D cortical bone models, will allow optimizing experimental conditions and solutions to inverse problems.
  • ex vivo validation of US biomarkers using a multimodal approach including US, X-ray µCT and mechanical tests.
  • clinical study to assess the predictive value of the US biomarkers for fracture risk prediction

Originality, assets

Originality: While the objective with most of QUS approaches developed so far is to provide clinicians with a surrogate marker of axial BMD, our technique seeks to overcome the limitations of DXA by providing bone quality factors that are not currently properly measured.

Novelty: QUS for cortical bone is an active research area. Previous available technologies were limited to the measurement the velocity of the first arriving signal (FAS) (i.e., the earliest event of the multicomponent signal recorded at the receivers). In contrast, our approach records the full response of the WG, enabling to compute the so-called dispersion curves of guided waves. From it, with an inversion scheme, bone elastic and structural properties may be formally recovered.

Further, we have currently both the most advanced technology dedicated for a clinical use. The technology is supported by a patented transducer technology [6-8], associated with a patented signal processing method allowing the exploitation of several propagation modes [9,10]. Both patents have been licensed to the spin-off company AZALEE.

Significance: Our QUS technology applied to long bones such as the radius or tibia in combination with accurate wave propagation models is expected to yield new and more effective US-based biomarkers to predict fracture risk or monitor therapy. The research should therefore be of benefit to the patients. In addition, the presence of AZALEE, with whom the principal applicant (PA) is engaged in a technology transfer, should be considered as a significant contribution to the project.