Peter Augat

Effects of Mechanical Factors on the Fracture Healing Process

An interdisciplinary study based on animal experiments, cell culture studies, and finite element models is presented. In a sheep model, the influence of the osteotomy gap size and interfragmentary motion on the healing success was investigated. Increasing gap sizes delayed the healing process. Increasing movement stimulated callus formation but not tissue quality. Typical distributions of intramembranous bone, endochondral ossification, and connective tissue in the fracture gap are quantified. The comparison of the mechanical data determined by a finite element model with the histologic images allowed the attribution of certain mechanical conditions to the type of tissue differentiation. Intramembranous bone formation was found for strains smaller than approximately 5% and small hydrostatic pressure (<0.15 MPa). Strains less than 15% and hydrostatic pressure more than 0.15 MPa stimulated endochondral ossification. Larger strains led to connective tissue. Cell culture studies on the influence of strain on osteoblasts supported these findings. Proliferation and transforming growth factor beta production was increased for strains up to 5% but decreased for larger strains. Osteoblasts under larger strains (>4%) turned away from the principal strain axis and avoided larger deformations. It is hypothesized that gap size and the amount of strain and hydrostatic pressure along the calcified surface in the fracture gap are the fundamental mechanical factors involved in bone healing.

Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions.

The International Society for Clinical Densitometry (ISCD) has developed Official Positions for the clinical use of dual-energy X-ray absorptiometry (DXA) and non-DXA technologies. While only DXA can be used for diagnostic classification according to criteria established by the World Health Organization, DXA and some other technologies may predict fracture risk and be used to monitor skeletal changes over time. ISCD task forces reviewed the evidence for clinical applications of non-DXA techniques and presented reports with recommendations at the 2007 ISCD Position Development Conference. Here we present the ISCD Official Positions for quantitative computed tomography (QCT) and peripheral QCT (pQCT), with supporting medical evidence, rationale, controversy, and suggestions for further study. QCT is available for bone mineral density measurements at the spine, hip, forearm, and tibia. The ISCD Official Positions presented here focus on QCT of the spine and pQCT of the forearm. Measurements at the hip may have clinical relevance, as this is an important fracture site; however, due to limited medical evidence, definitive advice on its use in clinical practice cannot be provided until more data emerge.

Shear movement at the fracture site delays healing in a diaphyseal fracture model

This study tested the hypothesis that interfragmentary axial movement of transverse diaphyseal osteotomies would result in improved fracture healing compared to interfragmentary shear movement. Ten skeletally mature merino sheep underwent a mid‐diaphyseal osteotomy of the right tibia, stabilized by external fixation with an interfragmentary gap of 3 mm. A custom made external fixator allowed either pure axial (n = 5) or pure shear movement (n = 5) of 1.5 mm amplitude during locomotion by the animals. The movement of the osteotomy gap was monitored weekly in two sheep by an extensometer temporarily attached to the fixator. After 8 weeks the sheep were killed, and healing of the osteotomies was evaluated by radiography, biomechanical testing, and undecalcified histology. Shear movement considerably delayed the healing of diaphyseal osteotomies. Bridging of the osteotomy fragments occurred in all osteotomies in the axial group (100%), while in the shear group only three osteotomies (60%) were partially bridged. Peripheral callus formation in the shear group was reduced by 36% compared to the axial group (p < 0.05). In the axial group bone formation was considerably larger at the peripheral callus and in between the osteotomy gaps but not in the intramedullary area. The larger peripheral callus and excess in bone tissue at the level of the gap resulted in a more than three times larger mechanical rigidity for the axial than for the shear group (p < 0.05). In summary, fixation that allows excessive shear movement significantly delayed the healing of diaphyseal osteotomies compared to healing under axial movement of the same magnitude.

The effect of mechanical stability on local vascularization and tissue differentiation in callus healing

To investigate the influence of the stability of an osteotomy fixation on the local vascularization and tissue differentiation in callus healing, a transverse osteotomy of the right metatarsal with a gap size of 2 mm was performed in 10 sheep and stabilized with an external fixator. This fixator permitted a defined axial movement. Two groups of 5 sheep were each operated upon to allow 0.2 mm (group A) or 1 mm (group B) of axial movement. Nine weeks after surgery, the callus was dissected and histological sections prepared. The type of tissue and the vessel distribution were determined.

Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone

Fracture repair, which aims at regaining the functional competence of a bone, is a complex and multifactorial process. For the success of fracture repair biology and mechanics are of immense importance. The biological and mechanical environments must be compatible with the processes of cell and tissue proliferation and differentiation. The biological environment is characterized by the vascular supply and by many biochemical components, the biochemical milieu. A good vascular supply is a prerequisite for the initiation of the fracture repair process. The biochemical milieu involves complex interactions among local and systemic regulatory factors such as growth factors or cytokines. The mechanical environment is determined by the local stress and strain within the fracture. However, the local stress and strain is not accessible, and the mechanical environment, therefore, is described by global mechanical factors, e.g., gap size or interfragmentary movement. The relationship between local stress and strain and the global mechanical factors can be obtained by numerical models (Finite Element Model). Moreover, there is considerable interaction between biological factors and mechanical factors, creating a biomechanical environment for the fracture healing process. The biomechanical environment is characterized by osteoblasts and osteocytes that sense the mechanical signal and express biological markers, which effect the repair process. This review will focus on the effects of biomechanical factors on fracture repair as well as the effects of age and osteoporosis.

Effect of dynamization on gap healing of diaphyseal fractures under external fixation

We asked whether dynamization of externally fixed diaphyseal fractures could improve bone healing in comparison to rigid fixation of fractures having similar remaining gap sizes. To answer this question we evaluated metatarsal osteotomies in 12 sheep. The osteotomy with a 0.6-mm gap was stabilized with a specially designed high bending and torsional stiffness external ring fixator. Osteotomies in six sheep were stabilized rigidly (axial movement < 0.06 mm) or dynamically (axial movement 0.15-0.34 mm). The cyclical axial interfragmentary movement was caused by the load-bearing of the operated limb. With increasing healing time, the initially allowed movement was decreased by callus formation around the osteotomy. The reduction in interfragmentary movement was measured and monitored by a linear variable displacement transducer at the external fixator and a telemetry system. After 9 weeks the sheep were sacrificed and the healed bones were investigated biomechanically and histomorphologically. Compared to the rigidly fixed osteotomies, the dynamized osteotomies showed significantly (P < 0.05) greater (+41%) callus formation and 45% greater tensile strength of the newly formed bone in the cortical osteotomy gap. Histological analysis indicated that the effect of dynamization occurred mainly after the 5th week. RELEVANCE: From these results we conclude that dynamic fixation of diaphyseal gaps is advantageous in comparison to stable external fixation.

Correlation of bone mineral density with strength and microstructural parameters of cortical bone in vitro

The aim of this study was to evaluate the influence of microstructural parameters, such as porosity and osteon dimensions, on strength. Therefore, the predictive value of bone mineral density (BMD) measured by quantitative computed tomography (QCT) for intracortical porosity and other microstructural parameters, as well as for strength of cortical bone biopsies, was investigated. Femoral cortical bone specimens from the middiaphysis of 23 patients were harvested during total hip replacement while drilling a hole (dia. 4.5 mm) for the relief of the intramedullary pressure. In vitro structural parameters assessed in histological sections as well as BMD determined by quantitative computed tomography were correlated with yield stress, and elastic modulus assessed by a compression test of the same specimens. Significant correlations were found between BMD and all mechanical parameters (elastic modulus: r = 0.69, p < 0.005; yield stress: r = 0.64, p < 0.005). Significant correlations between most structural parameters assessed by histology and yield stress were discovered. Structural parameters related to pore dimensions revealed higher correlation coefficients with yield stress (r = -0.69 for average pore diameter and r = -0.62 for fraction of porous structures, p < 0.005) than parameters related to osteons (r = 0.60 for osteon density and average osteonal area, p < 0.005), whereas elastic modulus was predicted equally well by both types of parameters. Significant correlations were found between BMD and parameters related to porous structures (r = 0.85 for porosity, 0.80 for average pore area, and r = 0.79 for average pore diameter in polynomial regression, p < 0.005). Histologically assessed porosity correlated significantly with parameters describing porous structures and haversian canal dimensions. Our results indicate a relevance of osteon density and fraction of osteonal structures for the mechanical parameters of cortical bone. We consider the measurement of BMD by quantitative computed tomography to be helpful for the estimation of bone strength as well as for the prediction of intracortical porosity and parameters related to porous structures of cortical bone.

Far cortical locking can improve healing of fractures stabilized with locking plates.

BACKGROUND Locked bridge plating relies on secondary bone healing, which requires interfragmentary motion for callus formation. This study evaluated healing of fractures stabilized with a locked plating construct and a far cortical locking construct, which is a modified locked plating approach that promotes interfragmentary motion. The study tested whether far cortical locking constructs can improve fracture-healing compared with standard locked plating constructs. METHODS In an established ovine tibial osteotomy model with a 3-mm gap size, twelve osteotomies were randomly stabilized with locked plating or far cortical locking constructs applied medially. The far cortical locking constructs were designed to provide 84% lower stiffness than the locked plating constructs and permitted nearly parallel gap motion. Fracture-healing was monitored on weekly radiographs. After the animals were killed at week 9, healed tibiae were analyzed by computed tomography, mechanical testing in torsion, and histological examination. RESULTS Callus on weekly radiographs was greater in the far cortical locking constructs than in the locked plating constructs. At week 9, the far cortical locking group had a 36% greater callus volume (p = 0.03) and a 44% higher bone mineral content (p = 0.013) than the locked plating group. Callus in the locked plating specimens was asymmetric, having 49% less bone mineral content in the medial callus than in the lateral callus (p = 0.003). In far cortical locking specimens, medial and lateral callus had similar bone mineral content (p = 0.91). The far cortical locking specimens healed to be 54% stronger in torsion (p = 0.023) and sustained 156% greater energy to failure in torsion (p < 0.001) than locked plating specimens. Histologically, three of six locked plating specimens had deficient bridging across the medial cortex, while all remaining cortices had bridged. CONCLUSIONS Inconsistent and asymmetric callus formation with locked plating constructs is likely due to their high stiffness and asymmetric gap closure. By providing flexible fixation and nearly parallel interfragmentary motion, far cortical locking constructs form more callus and heal to be stronger in torsion than locked plating constructs.

Quantitative assessment of experimental fracture repair by peripheral computed tomography.

Abstract. An experimental fracture model was used to assess bone mineral density at the fracture site by peripheral computed tomography and to compare the model with biomechanical, histological, and radiographic methods for the quantification of the fracture repair process. Transverse osteotomies in the mid-diaphysis of 28 tibia of sheep were externally fixed and mineral densities, cross-sectional areas, flexural rigidities, tissue composition, and projected callus area were calculated after 9 weeks of healing time. BMD measured by pQCT was strongly correlated with histologically determined percentages of mineralized tissue in the osteotomy gap (R2= 0.71) and in the periosteal callus (R2= 0.62). The percentage of mineralized tissue in the osteotomy gap was the best predictor of the flexural rigidity of the tibiae (R2= 0.74). Because of high correlations with the histological findings, the volumetric BMD at the level of the osteotomy gap was also strongly correlated with the biomechanical findings (R2= 0.70). Neither the cross-sectional area in pQCT nor the projected callus area in plane film radiography were positively correlated to the flexural rigidity of the tibiae.Quantitative computed tomography proved to be a successful estimator for the prediction of the mechanical stability of healing bones. The noninvasive procedure is a reliable tool for the quantification of the fracture repair process in experimental studies and may be useful for treatment decisions in particular clinical situations.

Effects of Construct Stiffness on Healing of Fractures Stabilized with Locking Plates

The benefits of locked-plate fixation, which include improved fixation strength in osteoporotic bone1-3 and the ability to provide a more biologically friendly fixation construct4,5, have led to the rapid adoption of this technology. Biological fixation of comminuted fractures with locking plates relies on secondary fracture-healing by callus formation6,7, which is stimulated by interfragmentary motion in the millimeter range8,9. Secondary bone-healing can be enhanced by active or passive dynamization10,11. Conversely, bone-healing can be suppressed by rigid fracture fixation aimed at preventing interfragmentary motion12. Biomechanical studies have suggested that locked-plate constructs are stiff and suppress interfragmentary motion to a level that may be insufficient to reliably promote secondary fracture-healing1,13-15. Recent clinical studies substantiate the concern that the inherently high stiffness of locked-plate constructs suppresses callus formation, contributing to a nonunion rate of up to 19% seen with periarticular locking plates16,17. Deficient healing may also contribute to late hardware failures seen with locking plates18-20 since, in the absence of osseous union, constructs remain load-bearing and eventually fail by hardware fatigue or loss of fixation. This paper summarizes a line of research that addresses two questions of critical importance when using locked-plate constructs: 1. Does the high stiffness of locked-plate constructs suppress callus formation and fracture-healing? 2. Can a stiffness-reduced locked-plate technique, termed far cortical locking , improve fracture-healing, compared with standard locked plating, by providing flexible fixation and parallel interfragmentary motion? First, we will present the findings of biomechanical and clinical studies of the effect of construct stiffness on interfragmentary motion and fracture-healing with locking plates. Subsequently, studies that describe the function, benefits, and clinical application of far cortical locking are …