Influence of cement stiffness and bone morphology on the compressive properties of bone-cement composites in simulated vertebroplasty.

Vertebroplasty is widely used to treat vertebral compression fractures. Little is known about the influence of morphological parameters of the bone on the properties of the bone-cement composite. Furthermore, although generic finite element (FE) models have been suggested as a way to compute the values of these properties, their accuracy has not been established. In the experimental part of this study, we tested bovine cancellous bone and three different polymethylmethacrylate bone cements and determined six quasi-static uniaxial compressive properties of bone-cement composite specimens and 10 morphological parameters of the bone. For the FE work, we used two simulations, one being µFE and the other unit cell FE. In conclusion, we found that (1) for composite specimens, that relative contribution of the cement to the overall response of the composite increases with increasing cement stiffness; (2) the anisotropy ratio is the bone morphological property that exerts the most significant influence on the experimentally obtained compressive properties of the bone-cement composites determined; (3) the accuracy of the computed compressive properties of the composites ranged from low to high, depending on simulation method used. The largest errors, however, can partially be explained by difference in boundary conditions between the experimental testing and the simulation techniques. The lattermost finding points to the potential for simplified FE models being incorporated into automatic material mapping schemes in whole bone vertebra FE simulations.

Experimental and computational models to investigate the effect of adhesion on the mechanical properties of bone-cement composites.

A generic finite element approach was developed to study the effect of adhesion on the mechanical response of bone cement composites and validated against literature data. The results showed that a zero friction bone-cement (PMMA) interface conditions captured the results of the experimental testing better than assuming a fully bonded interface. An experimental model for studying the effect of interface adhesion in a bone-cement like composite was also developed in the present study. The results using this model indicate that the difference in Young's modulus and ultimate strength between a fully bonded interface and unbonded interface is approximately 30% for bone volume fraction similar to what can be found in osteoporotic vertebrae. Apart from concluding that bone to cement adhesion is a major contributor to the mechanical response of bone-cement composites, our studies based on the generic FE approach also indicate that the mechanical properties of the cement is the most important contributor to the resulting mechanical properties of the composite at bone volume fraction relevant in terms of vertebroplasty treatment.

Causes of death in rodent toxicity and carcinogenicity studies.

Peto test procedures for the statistical evaluation of carcinogenicity studies require that each tumor in an animal that died intercurrently (or was sacrificed in extremis) be classified as either fatal, probably fatal, incidental, or probably incidental. There is considerable controversy as to whether or not the cause of death can be established with accuracy in rodent studies. In the present article, the causes of death or ill-being as found in 10 consecutive carcinogenicity studies--5 studies with 2400 OFA (Sprague-Dawley-derived) and Wistar rats and 5 studies with 2400 OF1 and NMRI mice--were re-examined. A cause of death or moribund state had been established in more than 80% of the cases in rats and in more than 70% in mice. These causes were, in rats, mainly pituitary tumors, chronic progressive nephropathy (males), mammary gland tumors (females), and subcutaneous tumors (males); in mice, mainly hemolymphoreticular tumors, lung tumors, liver tumors (males), and glomerulonephropathy. The criteria used for determining the tumorous or non-tumorous lesions as the cause of death were based on in-life and pathological findings. The validity of such procedures, the possibility of improving criteria in the future, and the usefulness of establishing causes of death in safety assessment are discussed.