Click on the following link for the full article in PDF format:

Overuse Injuries: All The Small Things - PDF Article. Published in Podiatry Management, October 2010. Update on the latest theories and evidence on tendon injury and stress fractures. Updates on Achilles tendinopathy.

All organs and tissues are made from cells so it is at the cellular level we will find our solutions. Cells are responsible for the changes that can prevent, repair, or breakdown the biological materials of which we are made. Much of the origin of both injury and injury avoidance can be found in mechanics or more accurately in mechanobiology and mechanotransduction.

"All tissues derive from cells so it is at the cellular level we will find our solutions"

We'll add more material on the theory here on the web, but in the meantime click on the link above and enjoy the article.

 

Excerpt from PM Magazine: 2010
Overuse Injuries Of Tendon And Bone: All The Small Things
Author: Stephen M. Pribut, DPM

Introduction:

Exercise is good for what ails you. It can improve memory, lower the risk of chronic disease, lessen the risk of diabetes, heart disease, stroke, and contribute to maintaining a healthy body weight.  When done to excess, running can be the cause of overuse injuries and run you into the ground.

Overuse injuries occur frequently among runners, causing downtime, and having deleterious physical and emotional consequences.  What follows is an excerpt from the full PDF article linked above. Recent theories on cell and tissue mechanics are reviewed along with a discussion of bone and tendon overuse injuries in the full article.

Mechanobiology: Let’s Get Physical

When a patient presents with an overuse injury we often think of the clinical aspects of their problem. We may try to analyze the events that led up to the injury and how to improve their condition and return them to their sport. In doing so, and in the articles we select to read on overuse injuries, we often forget about what is going on at the cellular level. The genome has been one of the main focuses of discussions of performance and disease, but we should also look at a newly developing discipline: mechanobiology. (Ingber 2004; Ingber 2006; Chen 2008) Biochemistry, biophysics, physiology, anatomy, biomechanics, and cellular mechanics all come into play in this field with significance to a variety of clinical entities including overuse injuries. We think of the diabetic with a chronic ulceration and the distance runner as vastly different. However, many of the same tissue structures and components important in wound healing are also critical to the healing of overuse injuries.

For all the elegance of genomics and biochemistry, mechanics still plays a major role in health and disease. (Ingber 2003; Chen, Liu et al. 2010)The mechanical loading that occurs with each step and with each movement that a joint undergoes is critical to maintain healthy articular cartilage. Intermittent contractions of muscles and the mechanical forces of loading thereby applied to muscles, tendons and bone result in remodeling and reshaping of these tissues.

Julius Wolff, a nineteenth century anatomist, proposed in 1892, that bone remodeled according to the stresses placed upon it. (Wolff 1892) This has since become known as “Wolff’s Law”.  From this simple and clear observation we have progressed to the more general concept of mechanotransduction.

Cellular Mechanics and Mechanotransduction

It has become apparent that mechanical forces play a major role in the regulation of cellular activity.  (Ingber 2003; Ingber 2003) The role is becoming increasing clear for mechanical forces in biological and genetic activation, cellular proliferation, tissue morphogenesis, and even in the growth of malignant tissue. (Ingber 2003; Ingber 2004; Ingber 2005; Schriefer, Warden et al. 2005; Vogel and Sheetz 2006) Mechanotransduction is the method by which optimal mechanical stress acting on a cell is detected, thereby stimulating intracellular signaling, promoting cellular activity including cellular growth, and enhancing cell survival. The forces acting on the cell through mechanotransduction affects cellular morphology and architecture have an impact on the metabolism and genetic expression of the cell. It is important to realize that mechanical forces can strengthen and enhance repair of the connective tissue as well as acknowledging that aberrant forces can also stimulate the break down of that tissue. Mechanotransduction is just starting to be recognized as possibly being central to much of physical therapy and massage therapy. It is  likely one of the reasons why early mobilization following injury is helpful and may also contribute to the benefits of other mechanical therapies including taping, bracing and custom orthotics. (Ingber 2008)

Buckminster Fuller and the architecture of the cell

Donald Ingber used the term “tensegrity” to refer to the tensile integrity that cells exhibit as a result of their cytoskeleton. (Ingber 2010) The term was coined by Buckminster Fuller to describe structures made by the sculptor Kenneth Snelson in 1948. (Fuller 1961)  Fuller designed many of his own structures along similar principles.   

Snelson: Needle
The Needle -
Kenneth Snelson’s Tensegrity Sculpture


A tensegrity structure is self-supporting and includes a set of rigid elements such as struts with endpoints that are connected to each other by continuous tensile connectors such as strings. The internal balance and self created tensions create an equilibrium by virtue of the compression of struts and tension of strings which allows the structure to maintain its shape. Geodesic domes and self-supporting camping tents are examples of tensegrity structures.

The old concept of a cell as an amorphous blob of protoplasm surrounded by a gelatinous membrane is definitely out. This image of the cell does not allow for force transmission within the cell. Instead a specific “solid” cytoskeleton provides structure to the cell. (Ingber 2008)The cytoskeleton is made of three filament systems: microfilaments, intermediate filaments and microtubules. Microfilaments are made of actin that associates with myosin to make tension generating ‘contractile filaments’. Actin by itself can form a flexible network or self-assemble into rigid cross-linked bundles. Intermediate filament composition varies according to cell type. They are polymers made from a variety of proteins including keratin, desmin or vimentin. They form “flexible cables” extending from the cell surface to the cell center surrounding the nucleus.

The cellular architecture is essentially a network of what Ingber terms “molecular cables, ropes and struts that span from the nucleus to the surface membrane”. (Ingber 2010) He believes that the cell is no jello like blob, but rather its tensional integrity provides for shape stability or “tenseg-rity”.

 Tensional forces develop within the cell as the actomyosin filaments slide within the cell. These forces are transmitted and balanced both within the cell and may be transmitted to other cells via external adhesions to the extra-cellular matrix (ECM).

Mechanically, the cytoskeleton acts as a system of struts and strings to internally balance forces. The cell transforms mechanical forces into biochemical signals and actions. Ingber’s view has come to be widely accepted and mechanobiology has become a growing discipline. Ingber further demonstrated that integrins are the receptors transmitting  signals that result in changes to cell shape which regulate gene expression and DNA synthesis. Integrins are trans-membranous protein chains that are integrated into the cellular membrane extending from the extracellular space across the membrane into the intracellular space.

ECM and mechanics as a determinant of cellular control

The extracellular matrix (ECM) is a mix of a variety of materials. In a sense it creates a flexible network that essentially transforms mechanical loading into intracellular signals. Proteoglycan molecules (PG), integrins, and dystroglycan all combine to form a scaffold for the adhesion of cells. The forces transmitted through this network both activate cellular signaling pathways and initiate cellular cytoskeletal rearrangement. Growth factors contained within the ECM are released following mechanical stimulation. Integrins are thought to be the main sensors of tensile stress at the cell surface.  Extracellular matrix sites which interact with integrins include collagens, fibronectin, tenascin and laminin.
The biological processes which affect cell growth, differentiation, polarity, motility contractility, and apoptosis are all subject to the influence of mechanical forces acting on cells that alter their physical shape. Fibroblasts, chondrocytes and capillary endothelium can have their activity changed from growth to differentiation by a decrease in the stiffness or in the adhesivity (Ingber 2003. Diseases of Mechanotransduction) . Endothelial cells can be converted to increase their rate of apoptosis. Individual bone cells have been shown to produce new bone in response to mechanical stress in vitro, just as they do in aggregate in vivo. Tensional forces have been observed to promote capillary outgrowth in vitro. The studies performed have demonstrated the importance of physical force in altering cellular activities and behavior without reliance upon hormonal or cytokine influence.

[See PDF Table 1a: Selected Mechanical Therapies]
[See PDF Table 1b: Selected Diseases With Possible Mechanical Etiology]

Go With The Force

Tendon is usually viewed as a simple, unitary structure that transmit force. The reality may be more complicated. There is evidence that suggests that force is not transmitted evenly throughout the tendon. Stresses and strains may be distributed differently in deeper portions of the tendon in comparison with superficial sections. Studies in human patellar tendon have demonstrated different mechanical properties of the anterior and posterior portions of the tendon. (Haraldsson. Region specific mechanical properties of the human patella tendon. J Appl Physio 2006) This suggests that forces applied to a tendon would not be evenly distributed throughout a cross section of the tendon. It is possible that shear forces within the interfascicular spaces serve to stimulate collagen production in the fibroblasts.
While knowledge is rapidly increasing in the science of tendinopathy, we still know little about even the length of the collagen fibrils within a tendon. There is contradictory evidence on whether or not fibrils are continuous or discontinuous. If the tendon fibrils are continuous the local tension would be borne by an individual fibril. If the fibrils are discontinuous the forces would be transferred to the adjacent fibrils and shearing forces would be of greater significance. This leads directly to another question: Is the injury a microrupture of a tendon fibril or are the components of the ECM playing a major role in injury and being damaged by shear forces.
The movement, stretching, and dissipation of local strains could take place in either of or a combination of three possible mechanisms (Magnusson 2010)

  • The triple helix of the tropocollagen may elongate
  • The gap between longitudinally oriented fibers may increase
  • A relative slippage may occur between adjacent molecules.

Repetitive tensile loading mechanically alters the shape of the fibroblast cells in tendons. This plays a major role in the mechanotransduction of physical force into genetic and biochemical action. Over-loading may result in injury or a material fatigue of the tendon tissue. Too little stress will also have a major impact on cellular function. Somewhere between the extremes of too little or too much strain the tissue will reach a proper balance of synthesis and degradation of tissue.

Characteristics of Tendinopathy

Histology

Tendinopathic tissue demonstrate a variety of alterations to cellular structure, cellular function, and to the ECM. The fibroblasts (tenocytes) are reduced in number and more rounded. The ECM shows an increase in proteoglycans, glycosaminoglycans, and water. Collagen fibers are disorganized. Substance-P nerve fibers and adrenergic receptors are found. Apoptosis occurs to a significantly greater extent in tendinopathic tissue. Inflammatory cells are not seen.  These changes are outlined in Table [2]

Cyclic Loading And The Healthy Tendon

Normal tendon activity increases collagen synthesis, while inactivity lowers both the collagen synthesis and collagen turnover. Some amount of activity is necessary to spur normal collagen formation even in tendinopathic tissue. A question that is hard to answer is how much and what role should eccentric exercises play in the therapy of severely damaged tendon.
Mechanical loading causes an increase in mRNA linked to collagen expression and increased synthesis of collagen. IGF-1, transforming growth factor -β (TGF -β) , connective tissue growth factor (CCTGF) and interleukin 6 (IL-6) all increase in response to exercise. Strain loads lead to a 2 to 3 times increase in collagen formation which peaks 24 hours after exercise and remains elevated for up to 70 or more hours. Degradation of collagen proteins also increases after exercise and starts even sooner than the collagen formation. Proteolytic markers, MMPs and collagen degradation fragments are elevated after exercise for 18 to 36 hours. These changes decrease after adaptation to exercise. Unaccustomed exercise stresses the tissues more than accustomed exercise and has a greater impact on the balance of anabolism and catabolism. Insufficient recovery time (or the “too little rest” of the terrible too’s) is another likely key to tendinopathy.

 Angiogenesis:

Formation of new blood vessels is a feature of healing tissue and injured tendons. Angiogenesis is also factor in cancer, diabetic retinopathy, and macular degeneration. Vascular endothelial growth factor (VEGF) antagonists have recently been approved to treat macular degeneration and someday may be useful for tendinopathy. Angiogenesis is a factor in both tendinopathy and its recovery. Oncology research into vascular growth factors is also relevant to tissue healing and to cellular mechanics.  A recent article detailed both in vitro and in vivo factors and showed that the mechanical features and stiffness of the ECM had a substantial impact on angiogenesis via VEGFR2. (Mammoto, Connor et al. 2009) This study demonstrated the first known functional cross-antagonism between transcription factors of tissue morphogenesis. The antagonistic transcription factors, TFII-I and GATA2, control the genetic expression of the VEGF receptor VEGFR2. This thorough study showed that the VEGF system responded to both mechanical and chemical factors.

Bone Biology and Mechanobiology

Introduction:

Bone is a dynamic and ever changing tissue. It is part of an intricate system balanced in its resorption and production by mechanics and hormonal influences. While bone plays a structural role as a frame does to a building, it is a biological tissue that is capable of self-repair. Theories of bone development, functioning, modeling and remodeling have evolved. The mechanics of Wolff’s law ultimately led to a time when the surface electrical changes, hormonal influences, and biochemical and genetic factors were thought to be most significant. A good deal of research has focused on these aspects of bone healing, but there has been a resurgence of interest in the importance of physical and mechanical influences.

The adaptability of bone is well known. Julius Wolff, a nineteenth century anatomist, proposed in 1892, that bone remodeled according to the stresses placed upon it.

This has since become known as “Wolff’s Law”. (Wolff 1892) For many years the understanding of boney adaptation has been on the functional adaptation of bone as a tissue. Cells, however, are what make tissue what it is.  Although the general principle has been known for more than a century, the cellular mechanisms have not been well described.

From Wolff’s simple and clear observation, our understanding of the “how” of bone modeling and remodeling moves on to the more general concept of mechanotransduction. Mechanotransduction is the manner in which mechanical energy is transposed into an electrical or biochemical biological signal. It is likely that most, if not all eukaryotic cells are mechanosensitive and respond to external forces. The physical world has many signals detected by our senses and cells. Gravity, sound waves, light waves, temperature, pressure, shear forces and impact shock are all in our environment and change cellular functioning and ultimately structure. Adaptation to the physical environment has been the hallmark of life and its evolution. Signal detection and translation of these signals to biological information is the subject of study of mechanobiology. 

Mechanical stimulation at the cellular level

Osteocytes are thought to be the main mechanosensory cell of bone and the lacuno-canalicular network appears to be the mediator of the signals. (Burger and Klein-Nulend 1999) Strain related flow of fluid through this system mechanically activates the osteocytes and carries cell signaling molecules along with nutrients and waste products. Instead of gross loading forces, lamellar fluid flow and the resultant shearing forces are likely the important signal received by bone cells, while induced local strain may be an additional signal. Jumping, vibration, and muscle contraction all create a variety of potential signals. Low magnitude but high frequency bone strains have been found to be anabolic to bone. (Ozcivici, Luu et al. 2010) Disuse, aging, and sarcopenia all decrease direct loading of the bone and loading from muscle. This depresses the normal mechanical regulatory signal and results in bone loss. Exercise, vibration stimulation and other protocols will ultimately be useful in prescriptions for recovery from bone injury.

Osteocytes are enclosed in lacunae surrounded by concentric lamellar layers of boney matrix. The osteocytes are connected to their neighbors by a network of interconnecting canaliculi. Both the osteocytes and the bone lining cells are remnants of the osteoblasts that have performed the productive work. Osteoclasts and osteoblasts are considered regulatory cells of modeling and remodeling. The osteocytes are strain sensitive cells that translate mechanical signals derived from physical loads into biological activities. Osteocytes have dendritic processes that contact nearby cells at gap junctions and form a cellular network. The network extends from deep in the lacuna to the bone surface. Transduced signals are sent to both osteoblasts and osteoclasts.  Proposed mechanosensory sites include stretch activated and voltage sensitive calcium channels (VSCC), focal adhesion proteins such as focal adhesion kinase (FAK), proline rich tyrosine kinase 2 (Pyk2) which are linked to the membrane by integrins, and G protein-coupled receptor 9GPCR).

Bone has four surfaces which may undergo remodeling: the haversian system, trabecular, endosteal, and periosteal. Each surface differs in its response to remodeling signals. Appropriate mechanical stimulation received and mechanotransduced activates osteoblastic differentiation, proliferation and apoptosis. Low levels of stimulation through inactivity or low gravity environment results in reduced bone synthesis and increased osteoclastic activity at the periosteal, endosteal and trabecular surfaces. Aberrant forces also cause disruption of the normal balance of production and destruction of bone tissue.  Pavalko et. al. describe a synthesis of how tensegrity theory could effect a mechanical and molecular cascade that would act directly on the nucleus. (Pavalko, Norvell et al. 2003) Their pithy conclusion was that “bending bones ultimately bend genes”.

The magnitude, duration and frequency of the load modulate the response of the skeleton. (Schriefer, Warden et al. 2005) The mechanism underpinning mechanodetection and differentiation of signals resulting from axial loading, torsion, bending forces and shearing forces remains to be worked out. Papachristou et. al. (2009) recently summarized the currently hypothesized metabolic pathways triggered by mechanical stimuli. (Papachristou, Papachroni et al. 2009) Several contributing pathways have been mapped. Prostaglandin synthetase (PGES) and COX 1/2 assist in the production of PGE2 .  COX-2 is also activated by PI3K/Akt and Wnt/ β-Catenin. Mechanical loading activates L type voltage sensitive calcium channel (L-VSCC), which allows the entrance of extracellular calcium to enter the cellular cytoplasm inducing intracellular calcium release.

Mitogen-activated protein (MAP) kinases (MAPK) (serine and threonine kinases) are a major link between membrane receptors of environmental signals and altered gene expression. The MAPK cascade system ERK1/2 plays an integral role in upregulating COX-2. This correlates with research suggesting limiting NSAID use during early bone healing.(Simon and O'Connor 2007)

The signaling systems implicated in mechanotransduction: Ca++ signaling, Wnt/ β-catenin signaling, nitric oxide, prostaglandin signaling and integrin signaling pathways interact in a complex manner with the cells and the extracellular matrix (ECM).  The genes controlling osteoblastic differentiation, proliferation and survival respond by appropriate upregulation and down regulation.

Ultimately, delineating the mechanoresponsive genes, molecular pathways, and signals, which affect bone will have a major impact on therapy for bone healing, injury prevention, aging and osteoporosis.     

Stress Injuries and Stress Reactions of Bone: Update 2010

(Also see: Dr. Pribut On Stress Fractures, A Repetitive Stress Injury of Bone)

Background

Chronic repetitive stress injury of bone, most commonly called a "stress fracture" has been described in the literature for many years. Cases have appeared in the literature going back to the 1800's. Briethaupt, a Prussian military physician, first reported this injury in 1855. (Breithaupt 1855) He presented the first description of a metatarsal stress fracture when he noted swelling and pain in the feet of military recruits. In 1897, just a few years after William Roentgen created the first x-ray machine, radiographic examination (x-ray) revealed the nature of these injuries. Injuries such as these were called "march fractures" because of they commonly were seen in military recruits suddenly subject to long forced marches. (Stechow 1897)

Discussion and Definition:

Stress-related bone injuries are frequent injuries among participants of running sports. In the absence of a visible fracture line, the bone is reacting to the stress, but it is not overtly cracked. X-rays may show periosteal bone formation, cortical thickening, or endosteal bone formation. Usually there is a discrete area of boney tenderness. The out of favor term “stress fracture” implies a physical crack, which is how engineers think of stress or “fatigue” fractures. However, stress reaction or stress-related injury of bone better fit the overuse injury observed.

The initial injury might be a biological or biochemical abnormality or failure at the cellular or Bone Multicellular Unit (BMU) level. Bone adapts to many levels of intermittent, repetitive compressive and tension strains by an increase in density. However, in the presence of abnormally high and repetitive forces the ability to heal from microdamage is not adequate. (Akkus and Rimnac 2001) These excessive repetitive stresses occur without the bone having adequate rest to allow for adaptation to stress. The stress that creates these injuries is too much, too soon for the bone.

Runners most often injure the tibia, metatarsals, calcaneus, or cuboid. But all lower extremity bones may be affected including the femur, navicular, fibula, pelvis, and cuneiform bones. Excessive repetitive forces, which may be compressive, tensile, or complex, result in injury to the bone. The bone cells begin a process of resporption without significant bone production. The forces contributing to the injury are both directly transmitted and also include forces generated by the “pull” of ligaments and tendons on the bone. Besides these external stressors to bone, the haversian canals are subject to internal sheer forces created by fluid flow. The initial injury seems to be to the bone matrix itself and is hard to clinically measure or detect.
[Insert Image 3 – “Calcaneal Stress Fracture” – Note that the stress fracture is anterior to the insertion of the Achilles tendon. This occurred after the patient began using a shoe which forced a forefoot landing, increasing the tension in the Achilles tendon. This demonstrates the devastating effect that tension can have on bone. ]

Injury may first be seen on a bone scan (scintigraphy) reflecting metabolic activity of bone. Slightly later the injury will be visible on an MRI. Finally the injury may become visible on an x-ray. Microfractures have been thought to be the physical precursor to stress related injury of bone but the reality is quite subtle. Mechanical forces activate the cell signaling mechanisms. Integrins, membrane proteins, thought to be a part of the cell sensing system, appear to play a role in the activation. Aberrant forces alter the subtle balance between osteoclastic and osteoblastic activity through altered gene activity. This mechanotransduction of force into biological mechanism is the true precursor to the stress related injury of bone. Cell signaling alters the gene activation pattern which then changes the metabolic activity of the cells. The altered metabolic activity causes aberrant remodeling which is a component of the initial stress “reaction” and not a true fracture.

Contributing Factors

Training Errors:

Training errors may be one of the greatest contributors to this injury. A change in training such as increasing the frequency, intensity, or duration too quickly may contribute. What has been termed the “terrible too’s” of too much, too soon, too often, too fast, with too little rest cumulatively over stress the bone before it can appropriately react to the stress by reinforcing itself.

Increased forces into the bones of the foot and leg are generated in the presence of fatigue. A new budding marathoner may be subject to more fatigue than an experienced runner if they rapidly build up their long runs. Fatigued muscles can not properly position the bones, slow the forces, or attenuate the forces in any of several ways that normally functioning muscles may do. Always emphasize to your patients to “...avoid doing too much too soon.”

Equipment Errors:

An improper match of foot type and shoe structure may contribute to a chronic repetitive stress injury to bone (stress fracture, stress reaction). Old, worn out shoes, are obvious contributors to injuries of all sorts.

Running on a hard and unyielding surface may increase forces into the bones of the foot and leg. Concrete can be a significant contributor to this injury.

Systemic Disorders:

A variety of systemic conditions can contribute to this injury. These conditions include osteopenia, osteoporosis, other metabolic bone disorder, hormonal abnormalities, inadequate nutritional intake, and collagen disorders. In women amenorrhea or oligomenorrhea may lead to deficient estrogen and low bone mineral density. Women with amenorrhea may be up to 5 times as likely to develop a stress-related injury of bone. (Shaffer, Rauh et al. 2006) The female athlete triad includes low bone density by definition along with disordered eating (or low energy availability) and amenorrhea. Energy availability is dietary energy intake minus exercise energy expenditure. Low energy availability appears to be the primary cause of impaired reproductive and skeletal health in the triad. (Nattiv, Loucks et al. 2007)

Overtraining may lead to decreased testosterone levels in men resulting in osteopenia. Patients of either gender having multiple stress fractures should undergo a bone density (DEXA) scan.

Bone Geometry, Muscle Strength

Muscle cross sectional area (MCSA) and bone geometry have been studied in relation to tibial stress fractures. A study of 39 female runners found that cortical bone strength, MCSA, and cortical area were all lower in those with stress fractures. (Popp, Hughes et al. 2009) Popp et. al. felt that greater muscle strength may prevent tibial stress fracture by decreasing the torque and shear forces going into the bone.   Another study of 88 runners, male and female, found that tibial cortical cross-sectional area was inversely correlated with stress fracture and medial tibial stress syndrome. (Franklyn, Oakes et al. 2008)

Edwards et. al. suggested that running speed was a risk factor for tibial stress fracture. A mathematical model was created and analyzed. The result suggested that by decreasing the speed of running from 4.5 to 3.5 meters/sec the estimated risk of stress injury would decrease by 7%. (Brent Edwards, Taylor et al. 2010) This is not a dramatic reduction and real life data have indicated the opposite. Bijur et. al. studied 585 West Point cadets and found that injuries occurred less often in faster cadets. (Bijur, Horodyski et al. 1997)

Diagnosis:

Patients usually relate a sudden or sub-acute onset of pain. Questioning may reveal changes in exercise pattern or gear. Mileage may have recently increased, twice a day runs undertaken, aggressive speed work started or the athlete may have worn his last pair of running shoes too long or changed to a very different new pair of running shoes. Physical examination often demonstrates a focal area of tenderness. Not every bone is easily palpated; the pelvic bones, femur, talus, and midtarsal bones are notoriously difficult to examine. In the rearfoot and midfoot a high level of suspicion must be present to reach the diagnosis. Imaging studies are helpful in the diagnosis. A bone scan will offer early sensitivity to stress reactions. MRI scans and x-rays can also be helpful.

On the tibia, a horizontal line of tenderness is often the differentiating clinical sign from the vertical tenderness of medial tibial stress syndrome. However, spiral and vertical stress reactions can occur in the tibia. Immobilization in a Pneumatic walker for 4 to 6 weeks or more is often helpful for tibial stress fractures, and a variety of other stress injuries of bone. Calcaneal stress fractures may be suspected when there is tenderness upon lateral compression of the calcaneal body, rather than at the medial calcaneal tuberosity or tenderness that is only plantar to the calcaneus.

Stress fractures of the tarsal navicular should be suspected when there is tenderness on the dorsal aspect that extends proximally to distally. In addition to tenderness, tenderness to percussion or to the vibrations of a tuning fork have been used as pathognomonic signs.

Diagnostic imaging includes radiographic evaluation, technetium-99 bone scan, and MRI. Often an injury is not visible on radiographic examination. Bone scintigraphy is considered sensitive, while MRI is considered to be both sensitive and specific. (Niva, Sormaala et al. 2007) At early stages the MRI shows marrow edema as an increased STIR signal and in fat-suppressed T2 images. On T1 sequences a decreased signal is noted. (Stafford, Rosenthal et al. 1986). As the injury progresses to a stage of increasing severity a low signal fracture line and bone callus may be visible. A number of conditions may confound diagnosis and appear similar to stress fracture on certain imaging studies. In other cases asymptomatic bone marrow edema may be visible on MRI. (Niva, Sormaala et al. 2007)

Treatment:

Conservative treatment works well for most stress-injuries of bone. The pain of weight bearing needs to be eliminated. With the elimination of pain the forces should be sufficiently low for healing and remodeling to take place. Multiple authors have recommended the use of a pneumatic walker for tibial stress fractures.   (Fredericson, Bergman et al. 1995) (Swenson, DeHaven et al. 1997) This may be used alone or with crutches as needed. A cam walker, pneumatic walker or low pneumatic walker may alleviate pain faster and be clinically superior to a post operative shoe for stress reactions of the metatarsal area and for other foot stress reactions. An added benefit of the pneumatic walker is that it can be removed for exercise, bathing, and sleep.

Most lower extremity stress reactions take between 8 and 17 weeks for recovery. (Matheson, Clement et al. 1987) During recovery, one should guide the athlete to appropriate cross training activity. Swimming, bicycling, and maintenance of upper body strength should be implemented. Lower extremity exercises should be chosen as appropriate.

A phased return to activity allowing sufficient time for healing is the key to a successful return to activity. In clinical practice, the author has found that weaning from the pneumatic walker seems to lessen the time to comfortable exit from the walker and prevent pain from returning and the necessity of returning to the use of the pneumatic walker.

Walking should start first building up from 20 minutes to 50 minutes. Running should start gently, slowly with a slow build up. After an adequate aerobic base has been achieved a slow and gradual increase in other stressors may be added such as hill work, limited bursts of moderate speed and later more intense and structured speed work.

Summary and Conclusion:
Mechanics, mechanobiology, and tensegrity theory play a significant role in prevention of injury, maintenance of healthy tissue, and injury recovery. Research demonstrates that you can not just add growth factors at injured tissue and hope for the best. Physical therapy, stretching, strengthening, and custom orthotics all have a basis in mechanics that intersects with mechanotransduction.
A recent study has confirmed that custom orthotics are helpful for a variety of overuse injuries. (Mattila, Sillanpaa et al. 2010) Clinical observation suggests that the conformation of the shell to the foot may be more important to successful orthotic therapy than posting. Theories remain to be created and tested. Benno Nigg conceived his idea on muscle tuning as one possible mechanism for orthotic function. (Nigg and Wakeling 2001) Nigg felt that forces acting through the foot would create a “muscle tuning” effect that would dampen soft tissue vibrations and reduce the loading rate of bone, tendon and cartilage in the leg. Certainly this could lead to solving a portion of the puzzle. Tensegrity theory and mechanotransduction are other, fresh areas for investigation.
As clinicians what is most important is getting our patients back on the road participating in their chosen sports. Strive to keep up with the clinical literature, make your own systematic observations, keep theory in mind, and go with what works best. George Sheehan often said “we are all an experiment of one”. Those “ones” make more sense when we add them up with large clinical studies. However, we must be prepared to make changes in therapy based on how that one patient in front of you is responding.

“All models are wrong. But some are useful.” George Box

References

Akkus, O. and C. M. Rimnac (2001). "Cortical bone tissue resists fatigue fracture by deceleration and arrest of microcrack growth." J Biomech 34: 757-764.
Bijur, P. E., M. Horodyski, et al. (1997). "Comparison of injury during cadet basic training by gender." Arch Pediatr Adolesc Med 151(5): 456-461.
Breithaupt, J. (1855). " Zur pathologie des menschlichen fussess.  1855; 24:169-177." Medizin Zeitung 24: 169-177.
Brent Edwards, W., D. Taylor, et al. (2010). "Effects of running speed on a probabilistic stress fracture model." Clin Biomech (Bristol, Avon) 25(4): 372-377.
Burger, E. H. and J. Klein-Nulend (1999). "Mechanotransduction in bone--role of the lacuno-canalicular network." FASEB J 13 Suppl: S101-112.
Chen, C. S. (2008). "Mechanotransduction - a field pulling together?" J Cell Sci 121(Pt 20): 3285-3292.
Chen, J. H., C. Liu, et al. (2010). "Boning up on Wolff's Law: mechanical regulation of the cells that make and maintain bone." J Biomech 43(1): 108-118.
Franklyn, M., B. Oakes, et al. (2008). "Section modulus is the optimum geometric predictor for stress fractures and medial tibial stress syndrome in both male and female athletes." Am J Sports Med 36(6): 1179-1189.
Fredericson, M., A. G. Bergman, et al. (1995). "Tibial stress reaction in runners. Correlation of clinical symptoms and scintigraphy with a new magnetic resonance imaging grading system." Am J Sports Med 23(4): 472-481.
Fuller, B. (1961). "Tensegrity." Portfolio Art News Annual 4: 112-127.
Ingber, D. E. (2003). "Mechanobiology and diseases of mechanotransduction." Ann Med 35(8): 564-577.
Ingber, D. E. (2003). "Tensegrity I. Cell structure and hierarchical systems biology." J Cell Sci 116(Pt 7): 1157-1173.
Ingber, D. E. (2003). "Tensegrity II. How structural networks influence cellular information processing networks." J Cell Sci 116(Pt 8): 1397-1408.
Ingber, D. E. (2004). "The mechanochemical basis of cell and tissue regulation." Mech Chem Biosyst 1(1): 53-68.
Ingber, D. E. (2005). "Tissue adaptation to mechanical forces in healthy, injured and aging tissues." Scand J Med Sci Sports 15(4): 199-201.
Ingber, D. E. (2006). "Cellular mechanotransduction: putting all the pieces together again." FASEB J 20(7): 811-827.
Ingber, D. E. (2008). "Tensegrity and mechanotransduction." J Bodyw Mov Ther 12(3): 198-200.
Ingber, D. E. (2008). "Tensegrity-based mechanosensing from macro to micro." Prog Biophys Mol Biol 97(2-3): 163-179.
Ingber, D. E. (2010). "From cellular mechanotransduction to biologically inspired engineering: 2009 Pritzker Award Lecture, BMES Annual Meeting October 10, 2009." Ann Biomed Eng 38(3): 1148-1161.
Mammoto, A., K. M. Connor, et al. (2009). "A mechanosensitive transcriptional mechanism that controls angiogenesis." Nature 457(7233): 1103-1108.
Matheson, G. O., D. B. Clement, et al. (1987). "Stress fractures in athletes. A study of 320 cases." Am J Sports Med 15(1): 46-58.
Mattila, V. M., P. J. Sillanpaa, et al. (2010). "Can orthotic insoles prevent lower limb overuse injuries? A randomized-controlled trial of 228 subjects." Scand J Med Sci Sports.
Nattiv, A., A. B. Loucks, et al. (2007). "American College of Sports Medicine position stand. The female athlete triad." Med Sci Sports Exerc 39(10): 1867-1882.
Nigg, B. M. and J. M. Wakeling (2001). "Impact forces and muscle tuning: a new paradigm." Exerc Sport Sci Rev 29(1): 37-41.
Ozcivici, E., Y. K. Luu, et al. (2010). "Mechanical signals as anabolic agents in bone." Nat Rev Rheumatol 6(1): 50-59.
Papachristou, D. J., K. K. Papachroni, et al. (2009). "Signaling networks and transcription factors regulating mechanotransduction in bone." Bioessays 31(7): 794-804.
Pavalko, F. M., S. M. Norvell, et al. (2003). "A model for mechanotransduction in bone cells: the load-bearing mechanosomes." J Cell Biochem 88(1): 104-112.
Popp, K. L., J. M. Hughes, et al. (2009). "Bone geometry, strength, and muscle size in runners with a history of stress fracture." Med Sci Sports Exerc 41(12): 2145-2150.
Schriefer, J. L., S. J. Warden, et al. (2005). "Cellular accommodation and the response of bone to mechanical loading." J Biomech 38(9): 1838-1845.
Shaffer, R. A., M. J. Rauh, et al. (2006). "Predictors of stress fracture susceptibility in young female recruits." Am J Sports Med 34(1): 108-115.
Simon, A. M. and J. P. O'Connor (2007). "Dose and time-dependent effects of cyclooxygenase-2 inhibition on fracture-healing." J Bone Joint Surg Am 89(3): 500-511.
Stechow (1897). "Fussödem und Röntgenstrahlen." Deutsche Militärärztliche Zeitschrift 26: 465.
Swenson, E. J., K. E. DeHaven, et al. (1997). "The Effect of a Pneumatic Leg Brace on Return to Play in Athletes with Tibial Stress Fractures." Am. J. Sports Med. 25(June): 322 - 328.
Vogel, V. and M. Sheetz (2006). "Local force and geometry sensing regulate cell functions." Nat Rev Mol Cell Biol 7(4): 265-275.
Wolff, J. (1892). The Law of Transformation of Bones. Berlin, Verlag August Hirschwald.

Additional Resources:

Dr. Pribut On Stress Fractures, A Repetitive Stress Injury of Bone

The Science of Tendinopathy - Stephen Pribut, DPM

Shin Splints, Medial Tibial Stress Syndrome - Stephen Pribut, DPM

Dr. Pribut On Achilles Tendinopathy (tendinitis) in Runners