Osteomyelitis simply means an
infectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
of the
boneBones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
or
bone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. It can be usefully subclassified on the basis of the causative organism (pyogenic bacteria or mycobacteria), the route, duration and anatomic location of the infection.
Pathogenesis
In general, microorganisms may infect bone through one or more of three basic methods: via the bloodstream, contiguously from local areas of infection (as in
cellulitisCellulitis is a diffuse inflammation of connective tissue with severe inflammation of dermal and subcutaneous layers of the skin. Cellulitis can be caused by normal skin flora or by exogenous bacteria, and often occurs where the skin has previously been broken: cracks in the skin, cuts, blisters,...
), or penetrating
traumaTrauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
, including iatrogenic causes such as
joint replacementReplacement arthroplasty [from Greek arthron, joint, limb, articulate, + -plassein, to form, mould, forge, feign, make an image of], or joint replacement surgery, is a procedure of orthopedic surgery in which the arthritic or dysfunctional joint surface is replaced with an orthopaedic prosthesis...
s or internal fixation of
fractureA bone fracture is a medical condition in which there is a break in the continuity of the bone...
s or
root-canaledEndodontic therapy is a sequence of treatment for the pulp of a tooth which results in the elimination of infection and protection of the decontaminated tooth from future microbial invasion...
teeth. Once the bone is infected, leukocytes enter the infected area, and, in their attempt to
engulf the infectious organisms, release
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that
lyseLysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
the bone.
PusPus is a viscous exudate, typically whitish-yellow, yellow, or yellow-brown, formed at the site of inflammatory during infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection of pus within or beneath the epidermis is known as a pustule or...
spreads into the bone's blood vessels, impairing their flow, and areas of devitalized infected bone, known as
sequestra, form the basis of a chronic infection. Often, the body will try to create new bone around the area of
necrosisNecrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
. The resulting new bone is often called an
involucrumInvolucrum is a layer of new bone growth outside existing bone seen in pyogenic osteomyelitis. It results from the stripping off of the periosteum by the accumulation of pus within the bone, and new bone growing from the periosteum....
. On
histologicHistology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
examination, these areas of necrotic bone are the basis for distinguishing between
acuteIn medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....
osteomyelitis and
chronic osteomyelitis. Osteomyelitis is an infective process that encompasses all of the bone (osseous) components, including the bone marrow. When it is chronic, it can lead to bone
sclerosisIn medicine, sclerosis refers to the stiffening of a structure, usually caused by a replacement of the normal organ-specific tissue with connective tissue.Types include:...
and deformity.
Chronic osteomyelitis may be due to the presence of intracellular bacteria (inside bone cells). Also, once intracellular, the bacteria are able to escape and invade other bone cells. In addition, once intracellular, the bacteria becomes resistant to some antibiotics. These combined facts may explain the chronicity and difficult eradication of this disease. This results in significant costs and disability and may even lead to amputation. Intracellular existence of bacteria in osteomyelitis is likely an unrecognized contributing factor to its chronic form.
In
infantA newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
s, the infection can spread to the
jointA joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
and cause
arthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
. In
childBiologically, a child is generally a human between the stages of birth and puberty. Some vernacular definitions of a child include the fetus, as being an unborn child. The legal definition of "child" generally refers to a minor, otherwise known as a person younger than the age of majority...
ren, large subperiosteal
abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
es can form because the
periosteumPeriosteum is a membrane that lines the outer surface of all bones, except at the joints of long bones. Endosteum lines the inner surface of all bones....
is loosely attached to the surface of the bone.
Because of the particulars of their blood supply, the
tibiaThe tibia , shinbone, or shankbone is the larger and stronger of the two bones in the leg below the knee in vertebrates , and connects the knee with the ankle bones....
,
femurThe femur , or thigh bone, is the most proximal bone of the leg in tetrapod vertebrates capable of walking or jumping, such as most land mammals, birds, many reptiles such as lizards, and amphibians such as frogs. In vertebrates with four legs such as dogs and horses, the femur is found only in...
,
humerusThe humerus is a long bone in the arm or forelimb that runs from the shoulder to the elbow....
, vertebra, the
maxillaThe maxilla is a fusion of two bones along the palatal fissure that form the upper jaw. This is similar to the mandible , which is also a fusion of two halves at the mental symphysis. Sometimes The maxilla (plural: maxillae) is a fusion of two bones along the palatal fissure that form the upper...
, and the mandibular bodies are especially susceptible to osteomyelitis. Abscesses of any bone, however, may be precipitated by trauma to the affected area. Many infections are caused by
Staphylococcus aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
, a member of the normal
floraIn microbiology, flora refers to the collective bacteria and other microorganisms in an ecosystem . While the term microflora is widely used, it is technically a misnomer since the word root flora pertains to the kingdom plantae...
found on the
skin-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
and
mucous membraneThe mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s. In patients with sickle cell disease, the most common causative agent remains
Staphylococcus aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
, but
SalmonellaSalmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
species become proportionally more common pathogens than in healthy hosts.
Cause
| Age group |
Most common organisms |
| Newborns (younger than 4 mo) |
S. aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
, EnterobacterEnterobacter is a genus of common Gram-negative, facultatively-anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. Several strains of the these bacteria are pathogenic and cause opportunistic infections in immunocompromised hosts and in those who are on mechanical ventilation...
species, and group AThe group A streptococcus bacterium is a form of β-hemolytic Streptococcus bacteria responsible for most cases of streptococcal illness. Other types may also cause infection...
and B Streptococcus species |
| Children (aged 4 mo to 4 y) |
S. aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
, group AThe group A streptococcus bacterium is a form of β-hemolytic Streptococcus bacteria responsible for most cases of streptococcal illness. Other types may also cause infection...
Streptococcus species, Haemophilus influenzaeHaemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...
, and EnterobacterEnterobacter is a genus of common Gram-negative, facultatively-anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. Several strains of the these bacteria are pathogenic and cause opportunistic infections in immunocompromised hosts and in those who are on mechanical ventilation...
species |
| Children, adolescents (aged 4 y to adult) |
S. aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
(80%), group AThe group A streptococcus bacterium is a form of β-hemolytic Streptococcus bacteria responsible for most cases of streptococcal illness. Other types may also cause infection...
Streptococcus species, H. influenzaeHaemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...
, and EnterobacterEnterobacter is a genus of common Gram-negative, facultatively-anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. Several strains of the these bacteria are pathogenic and cause opportunistic infections in immunocompromised hosts and in those who are on mechanical ventilation...
species |
| Adult |
S. aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
and occasionally EnterobacterEnterobacter is a genus of common Gram-negative, facultatively-anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. Several strains of the these bacteria are pathogenic and cause opportunistic infections in immunocompromised hosts and in those who are on mechanical ventilation...
or StreptococcusStreptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
species |
| Sickle Cell Anemia Patients |
SalmonellaSalmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
species |
In children, the
long boneThe long bones are those that are longer than they are wide. They are one of five types of bones: long, short, flat, irregular and sesamoid. Long bones, especially the femur and tibia, are subjected to most of the load during daily activities and they are crucial for skeletal mobility. They grow...
s are usually affected. In adults, the vertebrae and the
pelvisIn human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...
are most commonly affected.
Acute osteomyelitis almost invariably occurs in children. When adults are affected, it may be because of compromised host resistance due to debilitation, intravenous drug abuse, infectious root-canaled teeth, or other disease or drugs (e.g., immunosuppressive therapy).
Osteomyelitis is a secondary
complicationComplication, in medicine, is an unfavorable evolution of a disease, a health condition or a medical treatment. The disease can become worse in its severity or show a higher number of signs, symptoms or new pathological changes, become widespread throughout the body or affect other organ systems. A...
in 1–3% of patients with pulmonary
tuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. In this case, the bacteria, in general, spread to the bone through the
circulatory systemThe circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
, first infecting the
synoviumSynovial membrane is the soft tissue found between the articular capsule and the joint cavity of synovial joints....
(due to its higher
oxygenOxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
concentration) before spreading to the adjacent bone. In tubercular osteomyelitis, the long bones and vertebrae are the ones that tend to be affected.
Staphylococcus aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
is the organism most commonly isolated from all forms of osteomyelitis.
Bloodstream-sourced osteomyelitis is seen most frequently in children, and nearly 90% of cases are caused by
Staphylococcus aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
. In infants,
S. aureus, Group B streptococci (most common) and
Escherichia coliEscherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
are commonly isolated; in children from 1 to 16 years of age,
S. aureus,
Streptococcus pyogenesStreptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...
, and
Haemophilus influenzaeHaemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...
are common. In some subpopulations, including intravenous drug users and
splenectomizedA splenectomy is a surgical procedure that partially or completely removes the spleen.-Indications:The spleen, similar in structure to a large lymph node, acts as a blood filter. Current knowledge of its purpose includes the removal of old red blood cells and platelets, and the detection and fight...
patients, Gram-negative bacteria, including enteric bacteria, are significant pathogens.
The most common form of the disease in adults is caused by injury exposing the bone to local infection.
Staphylococcus aureus is the most common organism seen in osteomyelitis, seeded from areas of contiguous infection. But anaerobes and Gram-negative organisms, including
Pseudomonas aeruginosaPseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
,
E. coli, and
Serratia marcescensSerratia marcescens is a species of Gram-negative, rod-shaped bacterium in the family Enterobacteriaceae. A human pathogen, S. marcescens is involved in nosocomial infections, particularly catheter-associated bacteremia, urinary tract infections and wound infections, and is responsible for 1.4% of...
, are also common. Mixed infections are the rule rather than the exception.
Systemic mycotic (fungal) infections may also cause osteomyelitis. The two most common are Blastomyces dermatitidis and
Coccidioides immitisCoccidioides immitis is a pathogenic fungus that resides in the soil in certain parts of the southwestern United States, northern Mexico, and a few other areas in the Western Hemisphere....
.
In osteomyelitis involving the vertebral bodies, about half the cases are due to
Staphylococcus aureus, and the other half are due to
tuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
(spread hematogenously from the
lungThe lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s). Tubercular osteomyelitis of the
spineIn human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
was so common before the initiation of effective antitubercular therapy that it acquired a special name,
Pott's diseasePott's disease is a presentation of extrapulmonary tuberculosis that affects the spine, a kind of tuberculous arthritis of the intervertebral joints...
.
Following laboratory analysis of clinical data and studied literature, we can say that the bone pathological changes are induced by several interrelated mechanisms the drug components, produced clandestinely. The
Burkholderia cepacia complexBurkholderia cepacia complex , or simply Burkholderia cepacia is a group of catalase-producing, non-lactose-fermenting Gram-negative bacteria composed of at least seventeen different species, including B. cepacia, B. multivorans, B. cenocepacia, B. vietnamiensis, B. stabilis, B. ambifaria, B....
have been implicated in vertebral osteomyelitis in intravenous drug users.
Diagnosis
Diagnosis of osteomyelitis is often based on
radiologicRadiology is a medical specialty that employs the use of imaging to both diagnose and treat disease visualized within the human body. Radiologists use an array of imaging technologies to diagnose or treat diseases...
results showing a lytic center with a ring of
sclerosisIn medicine, sclerosis refers to the stiffening of a structure, usually caused by a replacement of the normal organ-specific tissue with connective tissue.Types include:...
. Culture of material taken from a bone biopsy is needed to identify the specific pathogen; alternative sampling methods such as needle puncture or surface swabs are easier to perform, but do not produce reliable results.
Factors that may commonly complicate osteomyelitis are fractures of the bone,
amyloidosisIn medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
,
endocarditisEndocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves . Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or even on intracardiac devices...
, or
sepsisSepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
.
Treatment
Osteomyelitis often requires prolonged
antibioticAn antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
therapy, with a course lasting a matter of weeks or months. A PICC line or
central venous catheterIn medicine, a central venous catheter is a catheter placed into a large vein in the neck , chest or groin...
is often placed for this purpose. Osteomyelitis also may require surgical
debridementDebridement is the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue...
. Severe cases may lead to the loss of a limb. Initial first-line antibiotic choice is determined by the patient's history and regional differences in common infective organisms. A treatment lasting 42 days is practiced in a number of facilities. Local and sustained availability of drugs have proven to be more effective in achieving prophylactic and therapeutic outcomes.
In 1875, American artist
Thomas EakinsThomas Cowperthwait Eakins was an American realist painter, photographer, sculptor, and fine arts educator...
depicted a surgical procedure for osteomyelitis at Jefferson Medical College, in a famous
oil paintingOil painting is the process of painting with pigments that are bound with a medium of drying oil—especially in early modern Europe, linseed oil. Often an oil such as linseed was boiled with a resin such as pine resin or even frankincense; these were called 'varnishes' and were prized for their body...
titled
The Gross ClinicThe Gross Clinic, or, The Clinic of Dr. Gross, is an 1875 painting by American artist Thomas Eakins. It is oil on canvas and measures by . Dr. Samuel D. Gross, a seventy-year-old professor dressed in a black frock coat, lectures a group of Jefferson Medical College students...
.
Prior to the widespread availability and use of antibiotics,
blow fly larvaeIn everyday speech the word maggot means the larva of a fly ; it is applied in particular to the larvae of Brachyceran flies, such as houseflies, cheese flies, and blowflies, rather than larvae of the Nematocera, such as mosquitoes and Crane flies...
were sometimes
deliberately introducedMaggot therapy is a type of biotherapy involving the intentional introduction of live, disinfected maggots into the non-healing skin and soft tissue wound of a human or animal for the purpose of cleaning out the...
to the wounds to feed on the infected material, effectively scouring them clean.
Hyperbaric oxygen therapyHyperbaric medicine, also known as hyperbaric oxygen therapy , is the medical use of oxygen at a level higher than atmospheric pressure. The equipment required consists of a pressure chamber, which may be of rigid or flexible construction, and a means of delivering 100% oxygen...
has been shown to be a useful adjunct to the treatment of refractory osteomyelitis.
Open surgery is needed for chronic osteomyelitis, whereby the involucrum is opened and the sequestrum is removed or sometimes saucerization can be done
Fossil record
Evidence for osteomyelitis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. Osteomyelitis has been reported in fossils of the large carnivorous dinosaur
Allosaurus fragilis.
See also
- Brodie abscess
A Brodie abscess is a subacute osteomyelitis, which may persist for years before converting to a frank osteomyelitis. Classically, this may present after conversion as a draining abscess extending from the tibia out through the shin....
- Chronic recurrent multifocal osteomyelitis
Chronic recurrent multifocal osteomyelitis is also known as Chronic recurring multifocal osteomyelitis.-CRMO :Chronic recurrent multifocal osteomyelitis is a rare condition , in which the bones have lesions, inflammation, and pain. Its definition is evolving...
- SAPHO syndrome
SAPHO syndrome includes a variety of inflammatory bone disorders that may be associated with skin changes. These diseases share some clinical, radiologic, and pathologic characteristics....
- Garre's sclerosing osteomyelitis
Garre's sclerosing osteomyelitis is a type of chronic osteomyelitis.It is a rare disease. It mainly affects children and young adults. It is associated with dental caries ....
Further reading
- Mechanisms of Staphylococcus aureus invasion of cultured osteoblasts. Ellington JK, Reilly SS, Ramp WK, Smeltzer MS, Kellam JF, Hudson MC. Microb Pathog. 1999 Jun;26(6):317–23.
- Intracellular Staphylococcus aureus. A mechanism for the indolence of osteomyelitis. Ellington JK, Harris M, Webb L, Smith B, Smith T, Tan K, Hudson M. J Bone Joint Surg Br. 2003 Aug;85(6):918–21.
- Intracellular Staphylococcus aureus and antibiotic resistance: implications for treatment of staphylococcal osteomyelitis. Ellington JK, Harris M, Hudson MC, Vishin S, Webb LX, Sherertz R. J Orthop Res. 2006 Jan;24(1):87–93.