Towards novel measurements of remodeling activity in cortical bone: implications for osteoporosis and related pharmaceutical treatments.

Bone remodelling is performed by basic multicellular units (BMUs) that resorb and subsequently form discrete packets of bone tissue. Normally, the resorption and formation phases of BMU activity are tightly coupled spatially and temporally to promote relatively stable bone mass and bone quality. However, dysfunctional remodelling can lead to bone loss and is the underlying cause of osteoporosis. This review surveys how BMU activity is altered in postmenopausal, disuse and glucocorticoid-induced osteoporosis as well as the impact of anabolic and anti-resorptive pharmaceutical treatments. The dysfunctional remodelling observed during disease and following medical intervention bares many testable hypotheses regarding the regulation of BMU activity and may provide novel insights that challenge existing paradigms of remodelling dynamics, particularly the poorly understood BMU coupling mechanisms. Most bone remodelling research has focused on trabecular bone and 2D analyses, as technical challenges limit the direct assessment of BMU activity in cortical bone. Recent advances in imaging technology present an opportunity to investigate cortical bone remodelling in vivo. This review discusses innovative experimental methods, such as 3D and 4D (i.e. time- lapsed) evaluation of BMU morphology and trajectory, that may be leveraged to improve the understanding of the spatio-temporal coordination of BMUs in cortical bone.

Stressed volume estimated by finite element analysis predicts the fatigue life of human cortical bone: The role of vascular canals as stress concentrators.

The fatigue life of cortical bone can vary several orders of magnitude, even in identical loading conditions. A portion of this variability is likely related to intracortical microarchitecture and the role of vascular canals as stress concentrators. The size, spatial distribution, and density of canals determine the peak magnitude and volume of stress concentrations. This study utilized a combination of experimental fatigue testing and image-based finite element (FE) analysis to establish the relationship between the stressed volume (i.e., volume of bone above yield stress) associated with vascular canals and the fatigue life of cortical bone. Thirty-six cortical bone samples were prepared from human femora and tibiae from five donors. Samples were allocated to four loading groups, corresponding to stress ranges of 60, 70, 80, and 90 MPa, then cyclically loaded in zero-compression until fracture. Porosity, canal diameter, canal separation, and canal number for each sample was quantified using X-ray microscopy (XRM) after testing. FE models were created from XRM images and used to calculate the stressed volume. Stressed volume was a good predictor of fatigue life, accounting for 67% of the scatter in fatigue-life measurements. An increase in stressed volume was most strongly associated with higher levels of intracortical porosity and larger canal diameters. The findings from this study suggest that a large portion of the fatigue-life variance of cortical bone in zero-compression is driven by intracortical microarchitecture, and that fatigue failure may be predicted by quantifying the stress concentrations associated with vascular canals.

Stressed volume around vascular canals explains compressive fatigue life variation of secondary osteonal bone but not plexiform bone.

The fatigue life of bone illustrates a large degree of scatter that is likely related to underlying differences in composition and microarchitecture. Vascular canals act as stress concentrations, the magnitude and volume of which may depend on the size and spatial distribution of canals. The purpose of this study was to establish the relationship between vascular canal microarchitecture, stressed volume and the fatigue life of both secondary osteonal and plexiform bovine bone. Twenty-one cortical bone samples were prepared from bovine femora and tibiae and imaged using micro-computed tomography (µCT) to quantify canal diameter, canal separation and canal number. Samples were cyclically loaded in zero-compression to a peak magnitude of 95 MPa, and fatigue life was defined as the number of cycles until fracture. Finite element models were created from µCT images and used to quantify the stressed volume, i.e., the volume of bone stressed higher than a yield stress of 108 MPa. Fatigue life ranged from 162-633,437 cycles with the fatigue life of plexiform bone (n = 15) being more than 4.5 times longer than secondary bone (n = 6). The fatigue life of secondary bone was negatively correlated with canal diameter (r2 = 0.73) and canal separation (r2 = 0.56), while the fatigue life of plexiform bone was negatively correlated with canal separation (r2 = 0.41), but positively correlated with canal number (r2 = 0.36). Stressed volume was related to canal microarchitecture in secondary bone only, where canal diameters and canal separation were larger than approximately 50 µm and 200 µm, respectively. Consequently, stressed volume explained 89% of the fatigue life variance in secondary bone but was not related to the fatigue life of plexiform bone. These findings suggest that the volume of the stress concentration surrounding vascular canals is dictated by canal size and spacing and may play an important role in the fatigue failure of osteonal bone. We suspect that a larger stressed volume is more likely to encounter and facilitate the propagation of pre-existing microcracks, thereby leading to a reduction in fatigue life.