Ivan Hvid

Quantification of age-related changes in the structure model type and trabecular thickness of human tibial cancellous bone

Structure model type and trabecular thickness are important characteristics in describing cancellous bone architecture. It has been qualitatively observed that a radical change of trabeculae from plate-like to rod-like occurs in aging, bone remodeling, and osteoporosis. Thickness of trabeculae has traditionally been measured using model-based histomorphometric methods on two-dimensional (2-D) sections. However, no quantitative study has been published based on three-dimensional (3-D) methods on the age-related changes in structure model type and trabecular thickness for human peripheral (tibial) cancellous bone. In this study, 160 human proximal tibial cancellous bone specimens from 40 normal donors, aged 16 to 85 years, were collected. These specimens were micro-computed tomography (micro-CT) scanned, then the micro-CT images were segmented using optimal thresholds. From accurate 3-D data sets, structure model type and trabecular thickness were quantified by means of novel 3-D methods. Structure model type was assessed by calculating the structure model index (SMI). The SMI was quantified based on a differential analysis of the triangulated bone surface of a structure. This technique allows quantification of structure model type, such as plate, rod objects, or mixture of plates or rods. Trabecular thickness is calculated directly from 3-D images, which is especially important for an a priori unknown or changing structure. Furthermore, 2-D trabecular thickness was also calculated based on the plate model. Our results showed that structure model type changed towards more rod-like in the elderly, and that trabecular thickness declined significantly with age. These changes become significant after 80 years of age for human tibial cancellous bone, whereas both properties seem to remain relatively unchanged between 20 and 80 years. Although a fairly close relationship was seen between 3-D trabecular thickness and 2-D trabecular thickness, real 3-D trabecular thickness was significantly underestimated using 2-D method.

The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens

The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens was studied by non-destructive uniaxial compression to 0.4% strain using cylindrical specimens with different sizes and length-to-diameter ratios, and by comparing cubic and cylindrical specimens with the same cross-sectional area. Both the length and the cross-sectional area of the specimen had a highly significant influence on the mechanical behaviour (p less than 0.0001). Within the actual range of length (2.75-11.0 mm) the normalized stiffness (Youngs modulus) was related nearly linearly to the specimen length. This dependency on specimen length is suggested to be caused mainly by structural disintegrity of the trabecular specimens near the surface. The normalized stiffness (Youngs modulus) was also positively correlated to the cross-sectional area. This dependency on cross-sectional area is probably due to friction-induced stress inhomogeneity at the platen-specimen interface. A cube with side length 6.5 mm or a cylindrical specimen with 7.5 mm diameter and 6.5 mm length are suggested as standard specimens for comparative studies on trabecular bone mechanics.

A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage

In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabecular bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis.

AGE VARIATIONS IN THE PROPERTIES OF HUMAN TIBIAL TRABECULAR BONE

We tested in compression specimens of human proximal tibial trabecular bone from 31 normal donors aged from 16 to 83 years and determined the mechanical properties, density and mineral and collagen content. Youngs modulus and ultimate stress were highest between 40 and 50 years, whereas ultimate strain and failure energy showed maxima at younger ages. These age-related variations (except for failure energy) were non-linear. Tissue density and mineral concentration were constant throughout life, whereas apparent density (the amount of bone) varied with ultimate stress. Collagen density (the amount of collagen) varied with failure energy. Collagen concentration was maximal at younger ages but varied little with age. Our results suggest that the decrease in mechanical properties of trabecular bone such as Youngs modulus and ultimate stress is mainly a consequence of the loss of trabecular bone substance, rather than a decrease in the quality of the substance itself. Linear regression analysis showed that collagen density was consistently the single best predictor of failure energy, and collagen concentration was the only predictor of ultimate strain.

Age-related variations in the microstructure of human tibial cancellous bone

A thorough understanding of the microstructure of cancellous bone is crucial for diagnosis, prophylaxis, and treatment of age‐related skeletal diseases. Until now, little has been known about age‐related variations in the microstructure of peripheral cancellous bone. This study quantified age‐related changes in the three‐dimensional (3D) microstructure of human tibial cancellous bone. One hundred and sixty cylindrical cancellous bone specimens were produced from 40 normal proximal tibiae from 40 donors, aged 16–85 years. These specimens were micro‐computed tomography (micro‐CT) scanned, and microstructural properties were determined. The specimens were then tested in compression to obtain Youngs modulus.

Changes in the three-dimensional microstructure of human tibial cancellous bone in early osteoarthritis

We obtained medial and lateral subchondral cancellous bone specimens from ten human post-mortem proximal tibiae with early osteoarthritis (OA) and ten normal age- and gender-matched proximal tibiae. The specimens were scanned by micro-CT and the three-dimensional microstructural properties were quantified. Medial OA cancellous bone was significantly thicker and markedly plate-like, but lower in mechanical properties than normal bone. Similar microstructural changes were also observed for the lateral specimens from OA bone, although there had been no sign of cartilage damage. The increased trabecular thickness and density, but relatively decreased connectivity suggest a mechanism of bone remodelling in early OA as a process of filling trabecular cavities. This process leads to a progressive change of trabeculae from rod-like to plate-like, the opposite to that of normal ageing. The decreased mechanical properties of subchondral cancellous bone in OA, which are due to deterioration in architecture and density, indicate poor bone quality.

Recombinant human vascular endothelial growth factor enhances bone healing in an experimental nonunion model

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model. Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 microg VEGF, carrier alone or autograft. After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow. We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion.

Mechanical properties of trabecular bone. Dependency on strain rate

The effect of strain rate (epsilon) and apparent density (rho) on stiffness (E), strength (sigma u), and ultimate strain (epsilon u) was studied in 60 human trabecular bone specimens from the proximal tibia. Testing was performed by uniaxial compression to 5% specimen strain. Six different strain rates were used: 0.0001, 0.001, 0.01, 0.1, 1, and 10 s-1. Apparent density ranged between 0.23 and 0.59 g cm-3. Linear and non-linear regression analyses using strength, stiffness and ultimate strain as dependent variables (Y) and strain rate and apparent density as independent variables were performed using the following models: Y = a rho b epsilon c, Y = rho b(a + c epsilon; Y = (a + b rho)epsilon c, Y = a rho 2 epsilon c, E = a rho 3 epsilon c. The variations of strength and stiffness were explained equally well by the linear and the power function relationship to strain rate. The exponent was 0.07 in the power function relationship between strength and strain rate and 0.05 between stiffness and strain rate. The variation of ultimate strain was explained best using a power function relationship to strain rate (exponent = 0.03). The variation of strength and stiffness was explained equally well by the linear, power function and quadratic relationship to apparent density. The cubic relationship between stiffness and apparent density showed a less good fit. Ultimate strain varied independently of apparent density.

Total condylar knee arthroplasty: Prosthetic component positioning and radiolucent lines

Prosthetic positioning and overall postoperative alignment were studied in 138 consecutive total knee replacements, using the Insall/Burstein total condylar knee system. Overall alignment was within 7 +/- 5 degrees of valgus in 63 per cent of the knees, while tibial component positioning was within 4 degrees of tilt in any direction in 53 per cent of the knees. A radiolucency index incorporating width and extent of radiolucent zones at the tibia was shown to progress from 3 months to 2 years postoperatively. The radiolucency index 2 years postoperatively was higher with postoperative varus alignment in the rheumatoid arthritis group; a tibial component tilt of more than 4 degrees in any direction increased the radiolucency index in both treatment groups.

X-RAY QUANTITATIVE COMPUTED TOMOGRAPHY: THE RELATIONS TO PHYSICAL PROPERTIES OF PROXIMAL TIBIAL TRABECULAR BONE SPECIMENS

Cylindrical bone specimens from the proximal epiphysis of ten normal human proximal tibiae were randomly assigned to a destructive axial compression test-series (N = 94) or to a protocol of standardized mechanical conditioning followed by non-destructive repeated testing to 0.6% strain and a final destructive test (N = 121). Specimen X-ray quantitative computed tomography (QCT) obtained at different scanning energies (100, 120 and 140 kVp) yielded closely related results (r = 1.00). Accordingly, predictions of physically measured densities or mechanical properties were not improved by using more than one scanning energy. QCT and physically measured densities were intimately related (QCT at 140 kVp to apparent density using linear regression: r = 0.94, and to apparent ash density: r = 0.95) and did not differ significantly in their ability to predict the mechanical properties, thus favouring the more easily implemented QCT for routine work. Evaluation of the relation of apparent density to Youngs modulus and ultimate strength suggested that a power law regression model is preferable to a linear model, although linear model prediction of mechanical properties does not have significantly worse accuracy within the narrow density range investigated. The effect of conditioning on the behaviour of bone specimens subjected to destructive compression tests was to increase the stiffness and strength by approximately 50 and 20% respectively.