Cortical pore size distribution, thickness and viscoelastic human tibia properties discriminate fragility fractures in postmenopausal women better than bone mineral density

Introduction Osteoporosis is a disorder of bone remodeling leading to reduced bone mass, structural deterioration, cortical thinning, and increased bone fragility. The current golden standard to predict bone status is based on the measurement of areal bone mineral density by dual energy x-ray absorptiometry (DXA), which poorly captures individual bone loss and structural decay. Enlarged cortical pores and reduced cortical thickness in the tibia have been proposed to indicate structural deterioration and reduced bone strength in the hip.

Methods In this cross-sectional study, we have assessed cortical pore parameters with two novel ultrasonic techniques. First, using cortical backscatter (CortBS) technology, were we assessed for the first time the cortical pore diameter distribution Ct.Po.Dm.D together with viscoelastic bone properties (i.e. slope and intercept of the frequency-dependent attenuation Ct.αf and Ct.αo ) at the anteromedial tibia midshaft. Second, using a refraction and phase aberration corrected multifocus (MF) imaging approach of the outer (periosteal) and inner (endosteal) cortical bone surface at the same location to determine cortical thickness Ct.Th and cortical speed of sound Ct.ν11. We hypothesized that the CortBS and MF biomarkers are associated with the occurrence of fragility fractures in postmenopausal women (N=55). The discrimination performance was assessed by means of multivariate PLS discrimination analyses with Leave-One-Out Cross-Validation (PLS-LOOCV) and benchmarked with models obtained from DXA and site-matched second-generation high-resolution peripheral computed tomography (HR-pQCT).

Results The short-term precision of the individual CortBS parameter estimations was in the range between 1.7 and 13.9%. Ct.Po.Dm values were in the range between 20 and 62.8 µm. CortBS parameters were associated with subject’s age (R²=0.44), height (R²=0.42), and marginally with weight (R²=0.27) and BMI (R²=0.24). Accuracy and precision were 0.18 mm and 6.61% for Ct.Th using cortical thickness values from HR-pQCT as reference values. CortBS+MF parameters were associated with subject’s age (R²=0.56), height (R²=0.42), weight (R²=0.41) and marginally with BMI (R²=0.23). We found a superior discrimination performance of CortBS (area under the receiver operating characteristic curve: 0.69≤AUC≤0.75) and of CortBS+MF (0.69≤AUC≤0.79) compared to DXA (0.53≤AUC≤0.55) and a similar performance compared to HR-pQCT (0.68≤AUC≤0.73).

Discussion CortBS and MF are quantitative bone imaging modality that can quantify viscoelastic and microstructural tissue deteriorations in cortical bone, which occur during normal aging and the development of osteoporosis. A widespread application of the method is anticipated to enable an early identification of people at increased risk, a timely initiation of preventive therapies, and subsequently to a reduction of the prevalence of fragility fractures in people with metabolic bone diseases.

Korrespondenzadresse Kay Raum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Deutschland, E-Mail: [e-mail]

Publication History

Article published online:
08 September 2022