Date Published: April 17, 2019
Publisher: Public Library of Science
Author(s): Gianluca Iori, Johannes Schneider, Andreas Reisinger, Frans Heyer, Laura Peralta, Caroline Wyers, Melanie Gräsel, Reinhard Barkmann, Claus C. Glüer, J. P. van den Bergh, Dieter Pahr, Kay Raum, Ryan K. Roeder.
Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 μm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMDneck) was measured by dual‐energy X‐ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMDneck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 μm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMDneck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo.
With >3.5 million fragility fractures annually in Europe only, osteoporosis represents a significant burden on the society . In elderly subjects, the hip is the most frequent and severe osteoporotic fracture site . In a population of increasing age, hip fractures represent a dramatic cause of functional decline, morbidity and mortality [3,4]. Despite these facts, a large number of hip fractures occurs in patients without diagnosed osteoporosis . The failure in detecting alterations of the cortical bone microstructure is considered one of the reasons of the only modest efficacy of the current DXA-based fracture risk assessment [6–8]. In an attempt to fill this diagnostic gap, studies have investigated the association of structural features in cortical bone with fracture risk [9,10]. One motivation for this has been the observation that in long bones, a reduction of the cortical thickness (Ct.Th) and an increase in the cortical porosity (Ct.Po) are responsible for the larger part of the age-related bone loss . Fueled by the advent of new technology such as high-resolution peripheral quantitative computed tomography (HR-pQCT), which allows the imaging of the distal skeleton in vivo with a spatial resolution down to 95 μm, clinical studies have associated Ct.Po and Ct.Th of the tibia and radius of humans with age, disease, fracture history, treatment and training [12–18].
In this work, we asked whether the cortical bone of the tibia can reflect changes in the stiffness and fracture resistance of the hip.
Recent evidence on intracortical bone remodeling have shown that an age-induced delay in osteoprogenitor recruitment following pore resorption leads to a progressive enlargement and accumulation of cavities in cortical bone . In this ex vivo study, the contribution to cortical porosity of canals with a diameter larger than 100 μm in the tibia of human donors was associated with reduced strength and stiffness of the proximal femur. The cortical bone of the tibia represents a key diagnostic opportunity for the prediction of the bone fracture risk since it is load bearing and can be measured in vivo by HR-pQCT and ultrasound. Our results indicate that cortical bone thickness and the prevalence of large voids in tibial cortical bone should be taken into account as biomarkers of a mechanical impairment of the hip, alternatively or in addition to standard DXA metrics.