Strength of bones depends on bone matrix volume (BMV), bone microarchitecture, and also on the degree of mineralization of bone (DMB). We have recently shown in osteoporotic patients treated with alendronate that fracture risk decreased and bone mineral density increased with a parallel increase of the DMB due to prolonged secondary mineralization but without modifications of BMV or bone microarchitecture. DMB and strength were both measured at the tissue level in calcaneus bone samples taken at autopsy from 20 subjects (aged 78 +/- 8 years, 8 women, 12 men) who died suddenly without apparent bone disease. DMB parameters measured on microradiographs (mean DMB, distribution of DMB, most frequent maximum DMB value, and width at half maximum, an index reflecting the homogeneity of DMB) were compared with those reported in iliac cancellous bone samples of 43 human bones. Histomorphometric measurements of microarchitectural parameters (TbTh, TbN, and TbSp) were also measured. Compression tests were performed on contiguous samples of the same calcaneus on a universal screw-driven machine (Schenck RSA 250). A 5000-N load cell (TME, F 501 TC) measured the compressive load. The displacement was measured directly on the sample using a specific displacement transducer developed by the <> The apparent Young's modulus (E), the maximal strength (sigma(max)), and the work (W) until failure were measured. In human cancellous bone tissue, mean DMB (+/- SD) was higher in calcaneus (1.135 +/- 0.147 g/cm(3)) than in iliac crest (1.098 +/- 0.077 g/cm(3)). The mean most frequent maximum DMB values (mean DMB freq. max.) were 1.118 +/- 0.175 g/cm(3) in calcaneus and 1.108 +/- 0.095 g/cm(3) in iliac samples, and DMB was more heterogeneous in calcaneus than in iliac samples (mean width at half maximum were 0.270 +/- 0.127 versus 0.227 +/- 0.056 g/cm(3), respectively). Compression tests revealed significant positive linear correlations between DMB and both elastic modulus (r(2) = 0.69) and maximal strength (r(2) = 0.69). Correlations with DMB persisted (P < 0.003) even after adjustment for both calcified bone volume, for the Young's modulus (E), the maximal strength (sigma(max)) (r(2) = 0.44 and 0.41, respectively), and microarchitectural parameters (0.50 < r(2) < 0.56, P < 0.001). The same results were obtained with the work to fracture (W) (0.23 < r(2) < 0.46, P < 0.045). We conclude that the more the cancellous tissue was mineralized, the higher was its stiffness and compressive strength. This may explain the increase in bone strength when DMB is modified in a physiological range without necessary changes of BMV and bone microarchitecture. The impact of such modifications on fracture risk and the therapeutic implications of these data remain to be analyzed.
The aim of the present study on human vertebral cancellous bone was to validate structural parameters measured with high-resolution (150 microm) computed tomography (HRCT) by referring to histomorphometry and to try to predict mechanical properties of bone using HRCT. Two adjacent vertical cores were removed from the central part of human L2 vertebral body taken after necropsy in 22 subjects aged 47-95 years (10 women, 12 men; mean age 79 +/- 14 years). The right core was used for structural analysis performed by both HRCT and histomorphometry. Two cancellous bone specimens were extracted from the left core: a cube for HRCT and a compression test, and a cylinder for a shear test. Significant correlations were found between HRCT and histomorphometric measurements (BV/TV, trabecular thickness, separation and number, and node-strut analysis), but with higher values for most of the tomographic parameters (BV/TV and trabecular thickness determined by HRCT were overestimated by a factor 3.5 and 2.5 respectively, as compared with histomorphometry). The maximum compressive strength and Young's modulus were highly correlated (rho = 0.99, p<0.0005). Significant correlation was obtained between bone mineral density (determined using dual-energy X-ray absorptiometry) and the maximum compressive strength (rho = 0. 64, p = 0.002). In addition the maximum compressive strength and architectural parameters determined by HRCT or histomorphometry showed significant correlations (e.g., for HRCT, BV/TV: rho = 0.88, p<0.0005, N.Nd/TV: rho = 0.73, p<0.001). The shear strength was significantly correlated with BV/TV (rho = 0.62, p = 0.002), Tb.Sp (rho = -0.58, p = 0.004) and TSL (rho = 0.55, p = 0.006) measured by HRCT. In conclusion, an HRCT system with 150 microm resolution is not sufficient to predict the true values of the structural parameters measured by histomorphometry, although high correlations were found between the two methods. However, we showed that a resolution of 150 microm allowed us to predict the mechanical properties of human cancellous bone. In vivo peripheral systems with such a resolution should be of interest and would deliver an acceptable radiation dose to the patient.
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