Effects of vertebral bone fragility and bone formation rate on the mineralization levels of cancellous bone from white females.

Back-scattered electron microscopy was used to study mineralization levels of human iliac cancellous bone of white females (N = 49). Mineralization levels were assessed by converting bone pixel grayscale levels to atomic number (Z) using known calibration standards. The data set consisted of bone biopsies from normal and vertebral fracture subjects that had either high or low values for bone formation rate (BFR(s)) within their respective groups (fracture/low BFR(s), N = 12; fracture/high BFR(s), N = 10; normal/low BFR(s), N = 12; normal/high BFR(s), N = 15). The following three measures of mineralization were quantitatively determined for each specimen: an overall mean mineralization (Z(mean)), the mineralization of trabecular packets deep within the interior of trabeculae (Z(deep)), and the mineralization of superficial exterior packets (Z(superficial)). Two-way analysis of variance revealed that the high BFR(s) group had a significantly lower Z(superficial) than the low BFR(s) group [mean (SD) 10.383 (0.270) vs. 10.563 (0.289)], and there was no significant interaction. BFR(s) had no effect on Z(mean) or Z(deep). For the pooled data, Z(deep) was significantly higher than Z(superficial) [10.866 (0.242) vs. 10.471 (0.291)]. There was no significant difference in Z(mean), Z(deep), or Z(superficial) between normals and those with vertebral fracture, but the standard deviations of the mineralization measures in the fracture group were at least double that of the normal group. Frequency histograms show that the two groups have fundamentally different mineralization distributions. The normal group demonstrates typical Gaussian distributions centered around the mean, and the distributions of the fracture group are bimodal, with peaks occurring at either the high or low tails of the distributions of the normal group. We hypothesize that both low and high patterns of mineralization might detrimentally affect bone material properties, with low mineralization levels causing reduced stiffness and strength and high mineralization resulting in reduced fracture toughness. The degree to which the mineralization differences may affect strength and stiffness of individual elements is estimated. The higher standard deviations of mineralization measures in the fracture group may reflect an inability to properly regulate trabecular level stress and strain. Forward stepwise regression analysis showed significant relationships between Ob.S/OS and both Z(superficial) and Z(mean), suggesting that the osteoblast may play an important role in regulating mineralization.

Cancellous bone mechanical properties from normals and patients with hip fractures differ on the structure level, not on the bone hard tissue level.

Osteoporosis is currently defined in terms of low bone mass. However, the source of fragility leading to fracture has not been adequately described. In particular, the contributions of bone tissue properties and architecture to the risk or incidence of fracture are poorly understood. In an earlier experimental study, it was found that the architectural anisotropy of cancellous bone from the femoral heads of fracture patients was significantly increased compared with age- and density-matched control material (Ciarelli et al., J Bone Miner Res 15:32-40; 2000). Using a combination of compression testing and micro-finite element analysis on a subset of cancellous bone specimens from that study, we calculated the hard tissue mechanical properties and the apparent (macroscopic) mechanical properties. The tissue modulus was 10.0 GPa (SD 2.2) for the control group and 10.8 GPa (SD 3.3) for the fracture group (not significant). There were no differences in either the apparent yield strains, percentages of highly strained tissue, or the relationship between apparent yield stress and apparent elastic modulus. Hence, a difference in the tissue yield properties is unlikely. At the apparent level, the fracture group had a significantly decreased transverse stiffness, resulting in increased mechanical anisotropy. These changes suggest that bone in the fracture group was "overadapted" to the primary load axis, at the cost of fragility in the transverse direction. We conclude that individuals with a history of osteoporotic fractures do not have weaker bone tissue. Architectural and mechanical anisotropy alone renders their bone weaker in the nonprimary loading direction.

Variations in three-dimensional cancellous bone architecture of the proximal femur in female hip fractures and in controls.

Cubes of cancellous bone were obtained from proximal femora of women with hip fractures (n = 26) and from female cadaveric controls (n = 32) to compare architecture and mechanics between groups. Specimens were scanned on a microcomputed tomography system. Stereologic algorithms and model-based estimates were applied to the data to characterize the three-dimensional cancellous microstructure. Cubes were mechanically tested to failure to obtain mechanical properties. Specimens from control subjects had significantly higher bone volume fraction, trabecular number, and connectivity than specimens from patients with hip fractures; no difference in trabecular thickness was observed between groups. Both maximum modulus and ultimate stress were significantly higher in the control than in the fracture group, consistent with the higher bone volume found in the control group. No statistical differences in any of these architectural or mechanical variables were found when groups were matched for bone volume. Specimens from both patients with hip fractures and controls demonstrated strong relationships between trabecular number and bone volume fraction that were statistically equivalent, suggesting that for a given bone mass, both groups have the same overall number of trabeculae. However, there was an architectural difference between fracture and control groups in terms of the three-dimensional spatial arrangement of trabeculae. Fracture specimens had a significantly more anisotropic (oriented) structure than control specimens, with proportionately fewer trabecular elements transverse to the primary load axis, even when matched for bone volume. Relationships between mechanical and architectural parameters were significantly different between groups, suggesting that fracture and control groups have different structure-mechanics relationships, which we hypothesize may be a consequence of the altered three-dimensional structure between groups.