Comparison of proximal femur and vertebral body strength improvements in the FREEDOM trial using an alternative finite element methodology.

Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.6%) strength in sideways fall configuration at 36 months, estimated in Newtons by an established voxel-based finite element (FE) methodology. Since FE analyses rely on the choice of meshes, material properties, and boundary conditions, the aim of this study was to independently confirm and compare the effects of denosumab on vertebral and femoral strength during the FREEDOM trial using an alternative smooth FE methodology. Unlike the previous FE study, effects on femoral strength in physiological stance configuration were also examined. QCT data for the proximal femur and two lumbar vertebrae were analyzed by smooth FE methodology at baseline, 12, 24, and 36 months for 51 treated (denosumab) and 47 control (placebo) subjects. QCT images were segmented and converted into smooth FE models to compute bone strength. L1 and L2 vertebral bodies were virtually loaded in axial compression and the proximal femora in both fall and stance configurations. Denosumab increased vertebral body strength by 10.8%, 14.0%, and 17.4% from baseline at 12, 24, and 36 months, respectively (p<0.0001). Denosumab also increased femoral strength in the fall configuration by 4.3%, 5.1%, and 7.2% from baseline at 12, 24, and 36 months, respectively (p<0.0001). Similar improvements were observed in the stance configuration with increases of 4.2%, 5.2%, and 5.2% from baseline (p≤0.0007). Differences between the increasing strengths with denosumab and the decreasing strengths with placebo were significant starting at 12 months (vertebral and femoral fall) or 24 months (femoral stance). Using an alternative smooth FE methodology, we confirmed the significant improvements in vertebral body and proximal femur strength previously observed with denosumab. Estimated increases in strength with denosumab and decreases with placebo were highly consistent between both FE techniques.

An experimentally validated finite element method for augmented vertebral bodies.

BACKGROUND: Finite element models of augmented vertebral bodies require a realistic modelling of the cement infiltrated region. Most methods published so far used idealized cement shapes or oversimplified material models for the augmented region. In this study, an improved, anatomy-specific, homogenized finite element method was developed and validated to predict the apparent as well as the local mechanical behavior of augmented vertebral bodies. METHODS: Forty-nine human vertebral body sections were prepared by removing the cortical endplates and scanned with high-resolution peripheral quantitative CT before and after injection of a standard and a low-modulus bone cement. Forty-one specimens were tested in compression to measure stiffness, strength and contact pressure distributions between specimens and loading-plates. From the remaining eight, fourteen cylindrical specimens were extracted from the augmented region and tested in compression to obtain material properties. Anatomy-specific finite element models were generated from the CT data. The models featured element-specific, density-fabric-based material properties, damage accumulation, real cement distributions and experimentally determined material properties for the augmented region. Apparent stiffness and strength as well as contact pressure distributions at the loading plates were compared between simulations and experiments. FINDINGS: The finite element models were able to predict apparent stiffness (R(2)>0.86) and apparent strength (R(2)>0.92) very well. Also, the numerically obtained pressure distributions were in reasonable quantitative (R(2)>0.48) and qualitative agreement with the experiments. INTERPRETATION: The proposed finite element models have proven to be an accurate tool for studying the apparent as well as the local mechanical behavior of augmented vertebral bodies.

The effect of standard and low-modulus cement augmentation on the stiffness, strength, and endplate pressure distribution in vertebroplasty.

PURPOSE: Vertebroplasty restores stiffness and strength of fractured vertebral bodies, but alters their stress transfer. This unwanted effect may be reduced by using more compliant cements. However, systematic experimental comparison of structural properties between standard and low-modulus augmentation needs to be done. This study investigated how standard and low-modulus cement augmentation affects apparent stiffness, strength, and endplate pressure distribution of vertebral body sections. METHODS: Thirty-nine human thoracolumbar vertebral body sections were prepared by removing cortical endplates and posterior elements. The specimens were scanned with a HR-pQCT system and loaded in the elastic range. After augmentation with standard or low-modulus cement they were scanned again and tested in two steps. First, the contact pressure distribution between specimen and loading plates was measured with pressure-sensitive films. Then, they were loaded again in the elastic range and compressed until failure. Apparent stiffness was compared before and after augmentation, whereas apparent strength of augmented specimens was compared to a non-augmented reference group. RESULTS: Vertebral body sections with fillings connecting both endplates were on average 33% stiffer and 47% stronger with standard cement, and 27% stiffer and 30% stronger with low-modulus cement. In contrast, partial fillings showed no significant strengthening for both cements and only a slight stiffness increase (<16%). The averaged endplate pressure above/below the cement was on average 15% lower with low-modulus cement compared to standard cement. CONCLUSION: Augmentation connecting both endplates significantly strengthened and stiffened vertebral body sections also with low-modulus cement. A trend of reduced pressure concentrations above/below the cement was observed with low-modulus cement.