C. A. Lill

Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images

There is increasing evidence that, in addition to bone mass, bone microarchitecture and its mechanical load distribution are important factors for the determination of bone strength. Recently, it has been shown that new high-resolution imaging techniques in combination with new modeling algorithms based on the finite element (FE) method can account for these additional factors. Such models thus could provide more relevant information for the estimation of bone failure load. The purpose of the present study was to determine whether results of whole-bone micro-FE (microFE) analyses with models based on three-dimensional peripheral quantitative computer tomography (3D-pQCT) images (isotropic voxel resolution of 165 microm) could predict the failure load of the human radius more accurately than results with dual-energy X-ray absorptiometry (DXA) or bone morphology measurements. For this purpose, microFE models were created using 54 embalmed cadaver arms. It was assumed that bone failure would be initiated if a certain percentage of the bone tissue (varied from 1% to 7%) would be strained beyond the tissue yield strain. The external force that produced this tissue strain was calculated from the FE analyses. These predictions were correlated with results of real compression testing on the same cadaver arms. The results of these compression tests were also correlated with results of DXA and structural measurements of these arms. The compression tests produced Colles-type fractures in the distal 4 cm of the radius. The predicted failure loads calculated from the FE analysis agreed well with those measured in the experiments (R(2) = 0.75 p < 0.001). Lower correlations were found with bone mass (R(2) = 0.48, p < 0.001) and bone structural parameters (R(2) = 0.57 p < 0.001). We conclude that application of the techniques investigated here can lead to a better prediction of the bone failure load for bone in vivo than is possible from DXA measurements, structural parameters, or a combination thereof.

Radius bone strength in bending, compression, and falling and its correlation with clinical densitometry at multiple sites.

This study comprehensively analyzes the ability of site‐specific and nonsite‐specific clinical densitometric techniques for predicting mechanical strength of the distal radius in different loading configurations. DXA of the distal forearm, spine, femur, and total body and peripheral quantitative computed tomography (pQCT) measurements of the distal radius (4, 20, and 33%) were obtained in situ (with soft tissues) in 129 cadavers, aged 80.16 ± 9.8 years. Spinal QCT and calcaneal quantitative ultrasound (QUS) were performed ex situ in degassed specimens. The left radius was tested in three‐point bending and axial compression, and the right forearm was tested in a fall configuration, respectively. Correlation coefficients with radius DXA were r = 0.89, 0.84, and 0.70 for failure in three‐point bending, axial compression, and the fall simulation, respectively. The correlation with pQCT (r = 0.75 for multiple regression models with the fall) was not significantly higher than for DXA. Nonsite‐specific measurements and calcaneal QUS displayed significantly (p < 0.01) lower correlation coefficients, and QUS did only contribute to the prediction of axial failure stress but not of failure load. We conclude that a combination of pQCT parameters involves only marginal improvement in predicting mechanical strength of the distal radius, nonsite‐specific measurements are less accurate for this purpose, and QUS adds only little independent information to site‐specific bone mass. Therefore, the noninvasive diagnosis of loss of strength at the distal radius should rely on site‐specific measurements with DXA or pQCT and may be the earliest chance to detect individuals at risk of osteoporotic fracture.

Bone Strength at Clinically Relevant Sites Displays Substantial Heterogeneity and Is Best Predicted From Site-Specific Bone Densitometry

In this study we test the hypotheses that mechanical bone strength in elderly individuals displays substantial heterogeneity among clinically relevant skeletal sites, that ex situ dual‐energy X‐ray absorptiometry (DXA) provides better estimates of bone strength than in situ DXA, but that a site‐specific approach of bone densitometry is nevertheless superior for optimal prediction of bone failure under in situ conditions. DXA measurements were obtained of the lumbar spine, the left femur, the left radius, and the total body in 110 human cadavers (age, 80.6 ± 10.5 years; 72 female, 38 male), including the skin and soft tissues. The bones were then excised, spinal and femoral DXA being repeated ex situ. Mechanical failure tests were performed on thoracic vertebra 10 and lumbar vertebra 3 (compressive loading of a functional unit), the left and right femur (side impact and vertical loading configuration), and the left and right distal radius (fall configuration, axial compression, and 3‐point‐bending). The failure loads displayed only very moderate correlation among sites (r = 0.39 to 0.63). Ex situ DXA displayed slightly higher correlations with failure loads compared with those of in situ DXA, but the differences were not significant and relatively small. Under in situ conditions, DXA predicted 50‐60% of the variability in bone failure loads at identical (or closely adjacent) sites, but only around 20‐35% at distant sites, advocating a site‐specific approach of densitometry. These data suggest that mechanical competence in the elderly is governed by strong regional variation, and that its loss in osteoporosis may not represent a strictly systemic process.

Biomechanical evaluation of healing in a non-critical defect in a large animal model of osteoporosis

Current methods for fracture treatment in osteoporosis are not always sufficient. To develop new fixation strategies (both mechanical and biological) requires pre‐clinical testing utilizing appropriate models. The aim of this study was to apply a recently developed sheep model of osteoporosis to the study of healing in a non‐critical long bone defect. A standardized transverse mid‐shaft tibial osteotomy (with a fracture gap of 3 mm) was performed in seven osteoporotic and seven normal sheep and stabilized with a special external fixator for 8 weeks. The fixator was used for weekly in vivo bending stiffness measurements. Ex vivo bending stiffness and torsional stiffness of the callus zone were also determined. Callus area, callus density, and osteoporosis status were determined at 0, 4, and 8 weeks using peripheral quantitative computed tomography. The increase of in vivo bending stiffness of the callus was delayed approximately 2 weeks in osteoporotic animals. A significant difference (33%) in torsional stiffness was found between the osteotomized and contralateral intact tibia in osteoporotic animals, but no significant difference occurred in normal sheep (2%). In osteoporotic animals, ex vivo bending stiffness was reduced 21% (p = 0.05). Bending stiffness was correlated with callus density (r = 0.76, r = 0.53); torsional stiffness was correlated with callus area (r = 0.60) and to a lesser extent with callus density (r = 0.53). This study demonstrated a delay of fracture healing in osteoporotic sheep tibiae with respect to callus formation, mineralization, and mechanical properties.

Can Novel Clinical Densitometric Techniques Replace or Improve DXA in Predicting Bone Strength in Osteoporosis at the Hip and Other Skeletal Sites

New peripheral techniques are now available for the diagnosis of osteoporosis, but their value in the clinical management of the disease remains controversial. This study tests the hypothesis that peripheral quantitative computed tomography (pQCT) at the distal radius and/or quantitative ultrasound (QUS) at the calcaneus can serve as replacement or improvement of current methodology (QCT and DXA) for predicting bone strength at the hip and other sites. In 126 human cadavers (age, 80.2 ± 10.4 years), DXA of the femur, spine, and radius and pQCT of the radius were acquired with intact soft tissues. QCT (spine) and QUS (calcaneus) were performed ex situ in degassed specimens. Femoral failure loads were assessed in side impact and vertical loading. Failure loads of the thoracolumbar spine were determined at three levels in compression and those of the radius by simulating a fall. Site‐specific DXA explained approximately 55% of the variability in femoral strength, whereas pQCT and QUS displayed a lower association (15‐40%). QUS did not provide additional information on mechanical strength of the femur, spine, or radius. All techniques displayed similar capability in predicting a combined index of failure strength at these three sites, with only QUS exhibiting significantly lower associations than other methods. These experimental results suggest that clinical assessment of femoral fracture risk should preferably rely on femoral DXA, whereas DXA, QCT, and pQCT display similar capability of predicting a combined index of mechanical strength at the hip, spine, and radius.

Bone Changes due to Glucocorticoid Application in an Ovariectomized Animal Model for Fracture Treatment in Osteoporosis

Abstract: In a pilot experiment comparing four different modalities for inducing osteoporosis in the sheep, a combination of ovariectomy, calcium/vitamin D-restricted diet and steroid administration was found to generate the highest decrease in bone mineral density (BMD). The aim of the present study was to quantify the outcome of this triple treatment in an animal model of osteoporosis in terms of alteration in bone mass, bone structure and bone mechanics. A total of 32 sheep were divided into two equal groups. Group 1 (age 3–5 years) was used as a normal control. Group 2 (age 7–9 years) was ovariectomized, fed a calcium/vitamin D-restricted diet and injected with methylprednisolone (MP) over 7 months (22 weeks MP solution, 6 weeks MP suspension). The BMD at the distal radius and tibia was determined preoperatively and at repeated intervals bilaterally using quantitative computed tomography. Steroid blood levels were determined 4 and 24 h after selected injections. BMD was measured at L3 and L4 after 7 months. Biopsies were taken from iliac crests, vertebral bodies and femoral heads, and bone structure parameters investigated by three-dimensional micro-CT. Compressive mechanical properties of cancellous bone were determined from biopsies of vertebral bodies and femoral heads. After 7 months of osteoporosis induction the BMD of cancellous bone decreased 36 ± 3% in the radius and 39 ± 4% in the tibia. Steroid blood levels 24 h after injection of MP suspension were significantly higher than after injection of MP solution. Changes in structural parameters of cancellous bone from the iliac crest, lumbar spine and femoral head in group 2 indicated osteoporosis-associated changes. In group 2 there was a significant reduction in BMD of the lumbar spine and a significant reduction in stiffness and failure load in compression testing of biopsies of lumbar vertebrae. In sheep, changes in the structural parameters of bone such as trabecular number and separation during osteoporosis induction are comparable to the human situation. The sheep model presented seems to meet the criteria for an osteoporosis model for fracture treatment with respect to mechanical and morphometric bone properties.

Effect of Ovariectomy, Malnutrition and Glucocorticoid Application on Bone Properties in Sheep: A Pilot Study

Abstract:The demographic changes in the human population continue to lead to an increasing incidence of osteoporosis. The main clinical symptom of osteoporosis is fracture. Fracture fixation in osteoporosis is frequently complicated by failure of fixation. There is a great need for a large-animal model of osteoporosis for controlled studies, which allows the investigation of fracture healing and fracture treatment in weak bone. Eight swiss mountain sheep, 7–9 years old, were divided into four treatment groups of two animals each. Group 1 was ovariectomized and fed a calcium/vitamin D-restricted diet (O+D). Group 2 was ovariectomized and given a daily intramuscular injection of 25 mg methylprednisolone (O+S). Group 3 was ovariectomized, fed a calcium/vitamin D-restricted diet and injected with 25 mg intramuscular methylprednisolone per day (O+D+S). Group 4 was used as an untreated, not sham operated control group. At the beginning of the study and every 2 months for 6 months the bone mineral density (BMD) was determined using quantitative computed tomography (pQCT) at the distal radius. Biopsies were taken after 6 months from vertebral bodies and femoral heads and the bone structure, i.e. trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), bone surface fraction (BS/BV) and bone volume fraction (BV/TV), was determined by micro-CT. In vitro compression testing of the biopsies was performed to determine failure load and stiffness. The control group showed no changes in BMD. The greatest decrease in BMD was seen in group 3 (O+D+S), which had a decline of 58% in cancellous bone and 22% in cortical bone. In the vertebral body biopsies a prominent change in structural parameters was observed (Tb.N, –53%; Tb.Th, –63%, Tb.Sp, +150%). The changes were less pronounced in the femoral head biopsies. In the compression test the vertebral body biopsies of group 3 (O+D+S) had stiffness values 40% lower failure load 70% lower compared with the control group. The most effective method of inducing osteoporosis in sheep was found to be the combined treatment. These results need to be confirmed in a larger number of animals.

Impact of bone density on distal radius fracture patterns and comparison between five different fracture classifications.

Objective To investigate the impact of bone mineral density (BMD) and bone geometry on failure loads and fracture patterns of the distal radius and to compare 5 different fracture classifications. Design Biomechanical and radiologic in vitro study. Setting Research laboratory. Main Outcome Measurements A total of 118 intact human forearms from elderly donors were examined by means of conventional radiography and peripheral quantitative computed tomography (PQCT) to determine BMD and geometry. The forearms were subjected to a standardized biomechanical test simulating a fall on the outstretched hand. The distal radius fractures were classified from x-rays using the AO (33), Cooney (9), Fernandez (15), Frykman (17), and Melone (31) classifications. The grading was repeated after preparation and direct visual inspection of the fracture site and was correlated with radiographic results. Fracture patterns also were correlated with BMD and geometry. Results Correlations between bone properties and fracture patterns (r = 0.09–0.70) suggested an increase in the severity of fractures with decreasing bone quality. The highest correlation between failure load and bone properties was found for the cortical area (r = 0.70) and trabecular density (r = 0.60). Good correlations between radiographic and direct visual classification were obtained for the Cooney (9) (r = 0.70), the AO (33) (r = 0.68), and the Fernandez (15) (r = 0.65) classifications. Smaller values were found for the Frykman (17) (r = 0.44) and the Melone (31) (r = 0.27) classifications. Conclusions With increasing osteopenia, the load to failure decreases, and the severity of fractures increases. Fracture patterns in this patient population can be adequately graded with the AO (33) and Cooney (9) classifications. The severity of distal radius fractures tends to be underestimated by conventional x-ray examination, which needs to be taken into account when a fracture treatment plan is selected.

Comparison of the in vitro holding strengths of conical and cylindrical pedicle screws in a fully inserted setting and backed out 180

Previous investigations have suggested that conical and cylindrical pedicle screws have comparable holding strengths. So far, the remaining performance in screws turned back or loose as a result of other reasons has not been determined. Twenty-four cadaveric spines from 6- to 8-week-old calves were examined. After bone mineral density was determined, four pedicle screws (two conical and two cylindrical screws) were inserted. The screws were fully inserted and half of them turned back 180 degrees. Twenty-four axial pullout and 24 cyclic loading tests with subsequent pullout tests were conducted. The pullout strengths of conical screws turned back 180 degrees are significantly smaller (1.8 kN) than those of cylindrical screws (4.3 kN). After cyclic loading, the displacement of conical screws is significantly greater (6.9 mm) than that of cylindrical screws (4.7 mm). Pedicle screws, especially conical ones, need to be placed to a correct depth, and they should not have to be backed out.

A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare

Summary Animal models are necessary to evaluate new options for the treatment of fractures in osteoporotic bone. They permit both the biological response of a living system and the influence of the pathological processes to be taken into account. A sheep model for osteoporosis was established by combining oestrogen deficiency, calcium and vitamin D-deficient diet with steroid medication. Bone mineral density (BMD) was reduced by >30% after 12 weeks of combined treatment. Osteoporosis similar to the human situation with corresponding changes in the micro-architecture and mechanical properties of bone was observed. This publication focuses on the impressive results obtained with the model and contrasts them with considerations of animal welfare. Considerable side-effects associated with steroid medication became manifest. Animals in the treatment groups showed signs of infection of various degrees due to the immunosuppressive effect of the medication. The infections were mostly caused by Corynebacterium pseudotuberculosis. Antibody testing revealed a 100% prevalence of infection in this breed of sheep. A modification of the steroid treatment, i.e. less-frequent injections, reduced the incidence of side-effects. This sheep model shows a significant and reproducible reduction in cancellous BMD of >30%, including relevant changes in biomechanical properties and increased fracture risk. However, the severity of the side-effects cannot be overlooked. The model must be improved if it is to be used in the future. Options to reduce the side-effects are discussed.