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 <<Laboratoire de Mécanique des Contacts et des Solides (LaMCoS).>> 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.