A Franco-German project funded by DFG and ANR

Duration: 3 years

Start: february 2015

Partners (coordinators):

Laboratory of Biomedical Imaging (LIB), Université Pierre et Marie Curie (Quentin Grimal)
Berlin-Brandenburg School for Regenerative Therapies, Charité – Universitätsmedizin, Germany (Kay Raum)
Osteoporosediagnostik, University of Kiel, Germany (Claus C Gluer)

Project

Osteoporosis (OP) is one of the most important global health problems of our aging population, which reduces mobility and quality of life, increases mortality, and sets dramatic burden to the healthcare system. OP and other degenerative bone pathologies are caused by a dis-balance between bone resorption and bone formation, leading to a rarefication of the trabecular network, and accumulation of partially refilled basic multicelluar units (BMUs) in cortical tissue. The latter result in cortical thinning, increased porosity, alterations of cortical bone stiffness and subsequently, to a reduction of bone strength. OP is considered as one of the most underdiagnosed diseases. Besides the limited applicability of ionizing radiations for longitudinal screening, it is now well accepted that dual X-ray absorptiometry (DXA), the established diagnostic tool for measuring bone mineral density, predicts only ~60% of the individual fracture risk and is not sensitive to the reduction of fracture risk upon response to treatment.

Bone strength assessment has long focused on trabecular bone, which is considered to be lost more rapidly than is cortical bone. This focus has neglected the role of the decay of cortical bone in the pathogenesis of bone fragility and in the incidence of fractures in women and men aged 65 years or more. Recent studies are pointing towards the importance of cortical bone, suggesting that diagnosis and risk assessment should include accurate evaluation of cortical bone. This motivates an important aspect of research in this proposal which is to focus measurements on cortical bone. Cortical bone loss is poorly captured by X-ray based techniques. Recently, innovative basic research on quantitative ultrasound has shifted towards measurements of cortical bone using guided and backscattered waves. Sophisticated approaches are currently explored in which, by solving an inverse problem, effective stiffness coefficients, intra-cortical porosity, and cortical thickness could be provided individually for each patient.

The aims of this concerted project are

• to establish novel ultrasound biomarkers of cortical bone loss, which allow quantitative assessment of cortical thickness, stiffness, and porosity using guided waves propagation by multidirectional axial transmission) and high-frequency pulse-echo backscatter measurement analyses, respectively;
• to relate these ultrasound biomarkers to local cortical bone strength at the measurement sites (tissue failure, mm-length scale) and to proximal femur strength (organ failure).

Measurements will be conducted ex-vivo in femur-tibia pairs from human donors. Structure, elastic and failure properties of cortical bone tissue will be determined at all measurement sites (tibia midshaft, proximal femoral shaft and femoral neck) by means of state-of-the art techniques, such as scanning acoustic microscopy, micro-computed tomography, resonance ultrasound spectroscopy, and mechanical failure testing. Proximal femur strength will be determined experimentally, in two mechanical loading configurations, and by high-resolution quantitative CT based finite element analysis.

Through this systematic survey we target early systemic and specific tissue changes that are strongly suspected to affect bone fragility and fracture risk. The targeted ultrasound biomarkers are anticipated to open perspectives in the diagnosis and longitudinal monitoring of bone pathologies.