BME/ME 456 Biomechanics
Biomechanics of Fracture Healing
In the section on mechanically mediated bone adaptation, we focused on how mechanics may affect bone per say through modeling and remodeling. In most cases, mechanics only significantly affects bone structure when modeling is enabled, either in adolescence or if loads are too high, or remodeling is enabled when loads are too small. The third classification of bone alteration is osteogenesis, the ability to change bone structure when laying bone down on soft tissues, either fibrous soft tissue or cartilage. In this section we will first review biological processes of fracture healing, discuss how these healing processes determine mechanical behavior of healing bone, discuss theories of how external mechanical stimulus can affect healing bone, and finally, discuss how these theories of healing and mechanical stimulus affect clinical fracture fixation treatments.
II. Biological Processes of Fracture Healing
As discussed in the section of your text on Biomechanics of Fracture Fixation (Chapter 9), there are three distinct phases of fracture healing: 1) inflammation, 2) reparation, and 3) remodeling. The first phase, inflammation, occurs immediately following the bone fracture. At that time, a hematoma or blood clot occurs at the fracture site. This hematoma provides two important factors important for fracture healing. First, the hematoma provides a small amount of mechanical stability to the fracture site. Second, and perhaps more importantly, the hematoma brings osteoblast, and chondrocyte precursors to the fracture site in large numbers that can begin to differentiate into osteoblasts and chondrocytes to begin producing matrix. In addition, macrophages and osteoclasts come into the site to remove damaged and necrotic tissue. Also, since bone fracture usually involves disruption of the periosteum surrounding the bone, more precursor cells from the periosteum will be introduced into the fracture site. The will begin the process of making a fracture callus through the general process of osteogenesis, laying down bone on soft tissue. Both types of osteogenesis, intramembranous and endochondral ossification may be occuring at the fracture site. The resulting proliferation of woven bone tissue will produce a fracture callus, bridging the fracture gap.
The second step in the biology of fracture healing is he reparation phase. In this phase, the processes of osteogenesis continue and a fracture callus bridges the fracture site. An example of histology of a callus from the pathology site //www-medlib.med.utah.edu/WebPath/BONEHTML/BONE015.html is shown below:
The bone again can be produced through intramembranous ossification, endochondral ossification or both. It is at this stage of fracture healing that external mechanical stimuli can have the greatest affect on fracture healing. This is because mechanical stability is crucial at this stage of fracture healing. Although it is not necessary to completely immoblize the fracture, and there is some debate about the need for small motion at the fracture site, it is definitely clear that too much motion will lead to a non-union. A non-union is the healing of a fracture site with soft tissue instead of bone. The desire to prevent non-unions is the reason that different types of fracture fixation devices are used in clinical practice.
The healed bony callus is formed of woven bone and primary bone. At this point, it consists of a large bony bridge connecting the two bones. The base material of the callus typically will have lower strength and stiffness than mature lamellar bone. It is the large mass of bone in the callus that gives the construct its strength. To reduce the callus mass while maintaining mechanical integrity the callus must be remodeled to produce the lamellar bone. During the remodeling period, the large fracture callus is reduced to become the size of the bone at the fracture site. The woven/primary bone is replaced with secondary lamellar bone. This process may take months or even up to a year or more in adults.
The steps of fracture healing may be summarized as follows:
1. Bleeding and fracture hematoma forms
3. Next 2-3 Days, granulation tissue formation
4. Osteogenic Cells invade tissue and lay down osteoid
5. At 3 weeks a soft callus forms consisting of osteoid and cartilage
6. Hard tissue callus forms in 6 - 12 weeks
7. Clinical union of bone ends occurs in 12 - 16 weeks
8. Remodeling of united fracture
III. Mechanical Properties of Healing Fracture Tissue
In keeping with the idea of bone structure function, each phase of fracture healing that has a different tissue type will also have different mechanical properties resulting from that tissue type. As outlined in your text, there is a tremendous change in a number of tissue parameters during fracture healing. For example, hydroxyproline, a constituent of type I collagen increases 2x. In addition, the amount of mineralized tissue within the fracture gap increases significantly. Of the structural parameters that have been related to fracture stiffness and strength, the size of the callus appears to be poorly related. Rather, it is the connectivity of the bone fragments across the fracture seem to correlate with overall fracture stiffness and strength. In addition, the amount of mineral have a significant influence on fracture stiffness and strength. The corresponds very well with structure-function relationships we discussed for normal bone, where Schaffler and Burr found a significant statistical relationship between degree of mineralization and stiffness for cortical bone. A graph below from your text illustrates the time versus hardness relationship:
The time frame is compressed because these measures were performed in rats, whose bone heals very quickly. The first ramp up in hardness coincides with callus formation and the increase in mineralization of granulation tissue. Following this, you will note a drop in hardness. This occurs at the beginning of the remodeling stage where bone is first resorbed by osteoclasts and then replaced by osteoblasts. As remodeling is complete and secondary bone is in place, the hardness is once again increased.
A classic study by White et al. (1977, Journal of Bone and Joint Surgery, "The four biomechanical stages of fracture repair", 59A:188-192), characterized the mechanical properties of healing fracture tissue into four stages. These four stages are as follows:
Bone fails through original fracture site; has low stiffness similar to soft tissue stiffness
Fracture site has low stiffness and low strength
Bone fails through original fracture site, but stiffness is more similar to mineralized tissue
Fracture site has normal bone stiffness but low strength
Bone fails partially through original site and partially through surrounding bone
Fracture site has normal bone stiffness and medium strength
Site of failure is not related to original fracture
Fracture site has normal bone stiffness and normal bone strength
When these stages are viewed with respect to tissue type, we can again see structure function relationships at work. In stage 1, we have primarily fibrous granulation tissue and possibly cartilage in the initial stages of osteogenesis. In Stage 2, we have begun to have woven bone. Since we have a large callus, we may have close to normal bone stiffness from the mass of the callus. However, woven bone does not have the strength of lamellar bone. In Stage 3, we have a mixture of woven and lamellar bone that increases overall strength. Finally, in stage 4, we have completely remodeled bone with normal bone stiffness and strength.
IV. Mechanical Effects on Fracture Healing: Theory
The premise that mechanical deformation and motion can affect the course of fracture healing has been postulated for many years. In the 1960's it was discovered that rigid fixation of a fracture site could lead to direct haversian bone healing without formation of an intermediate callus. This type of healing was called primary healing, while healing in which a callus was formed was called secondary healing. In fact, a whole orthopaedic movement and company in Switzerland and Germany grew based on the idea of primary fracture healing and internal rigid fracture fixation. This group was known as the AO.
Although the concept that mechanics can affect fracture healing has been around for a while, direct evidence or a mathematical theory relating mechanics to fracture healing has not been rigorously tested. The two main theories relating mechanical stimuli to fracture healing are one due to Perren and one due to Blenman and Carter. The one due to Perren is called the interfragmentary strain theory. It postulates changes in fracture gap tissue related to strain magnitudes in the fracture gap. Perren theorized that the magnitude of interfragmentary strain would determine the subsequent differentiation of fracture gap tissue. Interfragmentary strain was defined as the relative displacement of the fracture gap ends divided by the initial fracture gap width. This may be written as:
This definition of gap strain corresponds to a small deformation definition of strain. Perren theorized that interfragmentary strains above 100% would lead to non-union. Strains between 10 and 100% would lead to sustain intial fibrous tissue formation. Strains between 2 and 10% would lead to cartilage formation and an endochonral ossification formation. Strains under 2% would lead to direct bone formation and primary fracture healing. This theory is illustrated in the schematic below:
Perren based his ideas on the fact that tissues that were strained beyond their ultimate strain could not form in the gap. In addition to the strain affects on initial formation, Perren believed that once set in progress that once tissues formed they would stiffen the fracture gap, which in turn would lead to lower strains, which would allow formation of the next stiffest tissue and the cycle would repeat until all bone was formed.
Another theory relating mechanical stimulus to fracture healing tissue was proposed by Carter and Blenman. Their theory differs from Perrens in that it not only predicts that the magnitude of mechanical stimulus will affect fracture tissue differentiation, but also the type of mechanical stimulus. This theory is actually a subset of a broader theory developed by Carter and colleagues relating mechanical stimulus to tissue growth, remodeling and healing. In terms of fracture healing, Carter and Blenman believed that vascular supply to tissues was the primary factor determing tissue differentiation. Based upon the level of vascularity, they believed that both the magnitude and type of mechanical stress, bascially hydrostatic pressure versus octahedral shear stress, would affect the type of tissue within fracture sites. If a good vascular supply was available to tissues, Carter/Blenman believed that the following sequence would occur:
1. Fracture elicits osteogenic stimulus
2. If minimial cyclic stresses are present with good blood supply, bone will form directly
3. If high hydrostatic compressive stresses were present, fibrocartilage would form
4. If high tensile or shear stresses were present, fibrous tissue would form
5. If fibrocartilage forms, subsequent shear stresses would lead to bone formation
These events are summarized in the graphic below from Carter (1987, J. Biomechanics):
The hydrostatic pressure is represented as:
The octahedral shear stress is given as:
where s1, s2 and s3 are the three principal stresses. If the fracture gap had poor vascularity, then Carter/Blenman believed that producing bone would not be possible since bone is a highly metabolic tissue in need of good blood supply. They proposed the following graph in the case of poor blood supply:
In this case, even low magnitude stresses will produce fibrocartilage instead of bone. To predict whether tissue would differentiate into bone or fibrocartilage, Carter and colleagues developed the osteogenic index:
where I is the scalar value of the index, i is a given load case, c is the total number of different load cases, ni is the number of loading cycles for a given load case, Si is the cyclic octahedral shear stress (always positive), Di is the cyclic hydrostatic stress (negative if compression, positive if tension), and k is an empirical factor weighing the relative contributions of hydrostatic and shear stress to tissue differentiation. The higher the value of I the more likely that the tissue will ossify. Carter, Blenman et al. applied this theory to look at a case of fracture healing in long bone subject to one axial load and two bending moments. Their results (from Carter, 1987, J. Biomechanics) are shown below:
They felt that values of k greater than or equal to 2 most closely matched clinical results, showing callus formation outside the fracture gap with fibrocartilage forming within the fracture gap. These results indicated that tissue differentiation during fracture healing was most sensitive to hydrostatic pressure.
There are both similarities and differences between Perren's and the Carter/Blenman theory of mechanical effects on fracture healing. Both theories suggest that too high of a mechanical stimulus will prevent bone formation and lead to a non-union. Both theories also suggest that very low magnitudes of strain and stress will lead to direction bone formation. It is the areas in between on which the theories disagree. Perren believes only strain magnitude, strains between 2% and 10%, drive cartilage formation, while Carter and Blenman belived that the type of stress, hydrostatic versus octahedral, would drive cartilage formation. Clinical results suggest that the theories most closely match the extremes, ie low stress for bone, high stress/strain fibrous non-union, with the middle being less clear.
V. Applications of Mechanically Mediate Fracture Healing on Clinical Applications
All rigorous applications of mechanically mediated fracture healing theories are not common, aspects of these theories can be seen in the use of devices to fix and stabilize fractures. It is widely believed that some mechanical rigidity is needed for complex unstable fractures to prevent gap tissue stresses from becoming too high and preventing bone formation to heal the fracture. The fracture fixation devices include external fixators, internal plates, and intramedullary rods. An example of how these devices may relate to mechanically mediated fracture healing theories is shown below (from Chapter 9 in the text, p. 327):
In this case, the presence of the fixator carries most of the load since it is much stiffer than the initial fracture gap tissue. Because the deformation of the fracture gap tissue is low, fibrocartilage can form. Since it is stiffer than only fibrous tissue, it begins to share load with the fixator. Because the fixator stiffness remains the same, and the fracture gap stiffness has increased, the overall construct stiffness increases reducing strain in the fracture gap. This allows the cartilage tissue then to become calcified and turn to bone. Thus, by tuning the stiffness of the fracture fixation device we can hope to predict strains in the fracture gap and make sure the fracture healing process can proceed normally.
VI. Types and mechanical performance of fracture fixation devices
Although most common fractures can be treated by immobilization with a cast, again an effort to reduce strains at the fracture site, unstable and compound fractures most often must be treated surgically with fracture fixation devices. These devices fall into three categories depending mainly on whether the device is entirely within the skin (internal fixation) or comes out of the skin (external fixation) and if internal, whether the device is a plate that is screwed to the outside of the bone or a rod that goes down the center of the bone. Most often the choice of what device to use is based on clinical experience and surgical ease in placing the device.
External fixation is achieved by an external frame with pins sticking in through the skin into bone pieces above and below the fracture site. External fixation is appropriate mainly for long bone fixation, and finds its most common application in complex, compound tibial fractures. In this case, it may not be possible to plate the fracture is many fragments exist. Common external fixators are shown below from the text:
It is intuitive that the mechanical stability at the fracture gap that can be achieved using external fixators depends on the fixator construct stiffness that in turns depends upon the geometric configuration of the fixator. The means by which fixator geometric factors affect fixator stiffness is listed below:
1. Increased pin diameter increases fixator rigidity
2. Increased pin number increases fixator rigidity
3. Decreased side bar separation increases fixator rigidity
4. Decreased pin separation increases fixation rigidity
These factors indicate that under axial load and to some extent under bending loads fixator stiffness is determined by bending of the pins placed in the bone.
A second type of fracture fixation device is internal plate fixation. Compared to external fixators, the advantage of plate fixation is the ability to achieve much more mechanical rigidity at the fracture site and no external pins being a site of fixation. A disadvantage is the decision of whether or not to remove the plate following bone union and the risk for bone resorption under the plate. Some example plate fixators are shown below:
The goal of internal fixation is to place the fracture gap between the two sets of holes, place screws through the holes and through both cortices if possible. It is also desirable to angle the screws towards the fracture gap in order to create compression across the fracture gap. Plate fixation is most commonly used in complex bone fractures, such as the pelvis and craniofacial region where it is not possible to easily place external fixators and where no intramedullary canal exists for rod fixation.
The third commonly used method of fracture fixation is intramedullary rod fixation. This type of fixation is most commonly used for femoral shaft fracture. For the femoral shaft that is slightly bowed and subject to both axial and bending loads primary, the intramedullary rod allows faster ambulation of the patient because the rod can carry much of the initial load on the bone. If plates are used, they will be placed on the outside of the femoral shaft and subject to much high bending stresses under early ambulation and therefore may fail under fatigue. An example of intramedullary rod fixation is shown below (p. 337 in Chapter 9):
Factors that affect the rigidity of intramedullary nailing include the cross section of the rod, whether distal screws are used (especialy to increase torsional rigidity), and the material from which the rod is made. Although in general less stiff than either plate or external fixation, the advantage of intramedullary nailing for femoral shaft fixation is early ambulation, ease of surgery, and the ability to remove the rod relatively easily.
We next compare the mechanical properties of and fracture healing under different fixation devices. It is important to remember that the choice of fracture fixation is determined by a number of factors in addition to mechanical rigidity including ease of surgical implantation, anatomic site, patient compliance, risk of infection and complications and ease of removal. In a general comparison of external fixation, intramedullary rod fixation, and internal plate fixation in dog tibia tested under bending, aixal distraction and torsion, plate fixation was seen to consistently give the highest rigidity. Intramedullary rods and external fixators with half a frame were consistently low, while external fixation with full pins was close to plate fixation for bending and torsion. This is shown in the figure on p. 331 in the text and repeated below:
However, if plate and rod fixators are tested for femoral shaft fixation, we see that plates and interlocking intramedullary rods have similar bending stiffness:
In terms of how rigidity affects bone formation during fracture healing, the results at least qualitatively agree with theories. Better and faster bone formation is generally seen with plates, although in the long run bone mechanical properties are roughly equal under different methods of fixation as long as a threshold of adequate fixation is achieved. Some results comparing bone formation under plates and rods for canine tibia fractures are seen below:
Under fracture healing conditions, mechanical stimulus has a much larger affect on tissue adaptation, with the ability to affect the whole course of tissue differentiation from bone to cartilage to fibrous tissue. This greatly affects fracture treating with a need to surgically provide adequate mechanical stability at the fracture site reduce fracture tissue strains and allow bone formation. This agrees with bone adaptation theories because osteogenesis and modeling are physiologic pathways for mechanically mediate bone adaptation which have a much greater potential to change tissue structure.
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