Bone quantity and quality are considered the main predictors of bone mechanical properties (i.e., strength and fracture resistance). These factors deal with the morphology and chemical composition of bone and can be assessed by non-invasive techniques such as dual-energy x-ray absorptiometry (DXA), providing the bone mineral density (BMD) and the trabecular bone score (TBS). These parameters, and in particular BMD, are currently used as clinical predictors of fracture risk but do not provide information regarding the fatigue life. Bone is continuously subjected to fatigue loading and fatigue-induced damage can be crucial in fragility fractures. To probe the effect of fatigue-induced damage on bone microarchitecture and elucidate the effect of such damage on the bone clinical parameters, we combined fatigue testing on ex-vivo porcine trabecular bone samples with DXA measurements and μCT imaging. In addition, we performed interrupted cyclic tests at different load levels and measured fatigue-induced damage accumulation in the form of stiffness degradation. We also highlighted the change of clinical and microstructural parameters during the accumulation of fatigue-induced damage in interrupted fatigue tests. Our results suggest that the parameters obtained from the current non-invasive diagnostic protocols (i.e. μCT and DXA) are not able to assess the amount of fatigue-induced damage. This can be due to the fact that such techniques provide global parameters, whereas fatigue-induced damage is a local phenomenon, closely connected to the microarchitecture.

Bone’s resistance to fracture depends on several factors, such as bone mass, microarchitecture, and tissue material properties. The clinical assessment of bone strength is generally performed by Dual-X Ray Photon Absorptiometry (DXA), measuring bone mineral density (BMD) and trabecular bone score (TBS). Although it is considered the major predictor of bone strength, BMD only accounts for about 70% of fragility fractures, while the remaining 30% could be described by bone “quality” impairment parameters, mainly related to tissue microarchitecture. The assessment of bone microarchitecture generally requires more invasive techniques, which are not applicable in routine clinical practice, or X-Ray based imaging techniques, requiring a longer post-processing. Another important aspect is the presence of local damage in the bony tissue that may also affect the prediction of bone strength and fracture risk. To provide a more comprehensive analysis of bone quality and quantity, and to assess the effect of damage, here we adopt a framework that includes clinical, morphological, and mechanical analyses, carried out by means of DXA, μCT and mechanical compressive testing, respectively. This study has been carried out on trabecular bones, taken from porcine trabecular vertebrae, for the similarity with human lumbar spine. This study confirms that no single method can provide a complete characterization of bone tissue, and the combination of complementary characterization techniques is required for an accurate and exhaustive description of bone status. BMD and TBS have shown to be complementary parameters to assess bone strength, the former assessing the bone quantity and resistance to damage, and the latter the bone quality and the presence of damage accumulation without being able to predict the risk of fracture.