Osteomyelitis
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Osteomyelitis (OM) is the infectious
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
of
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
. Symptoms may include pain in a specific bone with overlying redness,
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
, and weakness. The feet, spine, and hips are the most commonly involved bones in adults. The cause is usually a bacterial infection, but rarely can be a fungal infection. It may occur by spread from the blood or from surrounding tissue. Risks for developing osteomyelitis include
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
, intravenous drug use, prior removal of the spleen, and trauma to the area. Diagnosis is typically suspected based on symptoms and basic laboratory tests as C-reactive protein and erythrocyte sedimentation rate. This is because plain
radiograph Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical ("diagnostic" radiography and "therapeu ...
s are unremarkable in the first few days following acute infection. Diagnosis is further confirmed by
blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...
s,
medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...
, or bone biopsy. Treatment of bacterial osteomyelitis often involves both antimicrobials and surgery. Treatment outcomes of bacterial osteomyelitis are generally good when the condition has only been present a short time. In people with poor blood flow,
amputation Amputation is the removal of a Limb (anatomy), limb or other body part by Physical trauma, trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as cancer, malign ...
may be required. Treatment of the relatively rare fungal osteomyelitis as
mycetoma Mycetoma is a chronic infection Subcutaneous tissue, in the skin caused by either bacteria (actinomycetoma) or fungi (eumycetoma), typically resulting in a triad of painless firm skin lumps, the formation of weeping sinus (anatomy), sinuses, and ...
infection entails the use of antifungal medications. In contrast to bacterial osteomyelitis, amputation or large bony resections is more common in neglected fungal osteomyelitis (mycetoma) where infections of the foot account for the majority of cases. About 2.4 per 100,000 people are affected by osteomyelitis each year. The young and old are more commonly affected. Males are more commonly affected than females. The condition was described at least as early as the 300s BC by
Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...
. Prior to the availability of antibiotics, the risk of death was significant.


Signs and symptoms

Symptoms may include pain in a specific bone with overlying redness,
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
, and weakness and inability to walk especially in children with acute bacterial osteomyelitis. Onset may be sudden or gradual. Enlarged lymph nodes may be present. In fungal osteomyelitis, there is usually a history of walking bare-footed, especially in rural and farming areas. Contrary to the mode of infection in bacterial osteomyelitis, which is primarily blood-borne, fungal osteomyelitis starts as a skin infection, then invades deeper tissues until it reaches bone.


Cause

Acute osteomyelitis almost invariably occurs in children who are otherwise healthy, because of rich blood supply to the growing bones. When adults are affected, it may be because of compromised host resistance due to debilitation,
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
drug abuse, infectious root-canaled teeth, or other disease or drugs (e.g., immunosuppressive therapy). The most commonly affected areas for children are the
long bone The 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 ...
s, and for adults, the feet, spine, and hips. Osteomyelitis is a secondary complication in 1–3% of patients with pulmonary
tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
. In this case, the bacteria, in general, spread to the bone through the
circulatory system In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart ...
, first infecting the synovium (due to its higher
oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
concentration) before spreading to the adjacent bone. In tubercular osteomyelitis, the long bones and vertebrae are the ones that tend to be affected.Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Mitchell, Richard N. (2007). ''Robbins Basic Pathology'' (8th ed.). Saunders Elsevier. pp. 810–11 ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
'' is the organism most commonly isolated from all forms of osteomyelitis. Osteomyelitis is often caused by ''Staphylococcus aureus''. In infants, ''S. aureus'', Group B streptococci and ''
Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'' are commonly isolated; in children from one to 16 years of age, ''S. aureus'', '' Streptococcus pyogenes'', and ''
Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, Motility, non-motile, Coccobacillus, coccobacillary, facultative anaerobic organism, facultatively anaerobic, Capnophile, capnophili ...
'' are common. In some subpopulations, including intravenous drug users and splenectomized patients,
Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...
, 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 aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...
'', ''E. coli'', and '' Serratia marcescens'', are also common. Mixed infections are the rule rather than the exception. Systemic mycotic infections may also cause osteomyelitis. The two most common are '' Blastomyces dermatitidis'' and '' Coccidioides immitis''. In osteomyelitis involving the vertebral bodies, about half the cases are due to ''S. aureus'', and the other half are due to
tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
(spread hematogenously from the
lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
s). Tubercular osteomyelitis of the spine was so common before the initiation of effective antitubercular therapy, it acquired a special name, Pott's disease. The ''Burkholderia cepacia'' complex has been implicated in vertebral osteomyelitis in intravenous drug users.


Pathogenesis

In general, microorganisms may infect bone through one or more of three basic methods * Via the bloodstream (''haematogeneously'') – the most common method * From nearby areas of infection (as in
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
), or * Penetrating trauma, including iatrogenic causes such as
joint replacement Joint replacement is a procedure of orthopedic surgery known also as arthroplasty, in which an arthritic or dysfunctional joint surface is replaced with an orthopedic prosthesis. Joint replacement is considered as a treatment when severe joint pai ...
s or internal fixation of
fracture Fracture is the appearance of a crack or complete separation of an object or material into two or more pieces under the action of stress (mechanics), stress. The fracture of a solid usually occurs due to the development of certain displacemen ...
s, leading to a fracture-related infection, or secondary periapical periodontitis in teeth. The area usually affected when the infection is contracted through the bloodstream is the
metaphysis The metaphysis (: metaphyses) is the neck portion of a long bone between the epiphysis and the diaphysis. It contains the growth plate, the part of the bone that grows during childhood, and as it grows it ossifies near the diaphysis and the ep ...
of the bone. Once the bone is infected,
leukocyte White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s enter the infected area, and, in their attempt to engulf the infectious organisms, release
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s that lyse the bone. Pus 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 necrosis. The resulting new bone is often called an involucrum. On histologic examination, these areas of necrotic bone are the basis for distinguishing between acute 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 sclerosis and deformity. Chronic osteomyelitis may be due to the presence of intracellular bacteria. Once intracellular, the bacteria are able to spread to adjacent bone cells. At this point, the bacteria may be resistant to certain antibiotics. These combined factors may explain the chronicity and difficult eradication of this disease, resulting in significant costs and disability, potentially leading to amputation. The presence of intracellular bacteria in chronic osteomyelitis is likely an unrecognized contributing factor in its persistence. In infants, the infection can spread to a joint and cause arthritis. In children, large subperiosteal abscesses can form because the
periosteum The periosteum is a membrane that covers the outer surface of all bones, except at the articular surfaces (i.e. the parts within a joint space) of long bones. (At the joints of long bones the bone's outer surface is lined with "articular cartila ...
is loosely attached to the surface of the bone. Because of the particulars of their blood supply, the
tibia The tibia (; : tibiae or tibias), also known as the shinbone or shankbone, is the larger, stronger, and anterior (frontal) of the two Leg bones, bones in the leg below the knee in vertebrates (the other being the fibula, behind and to the outsi ...
,
femur The femur (; : femurs or femora ), or thigh bone is the only long bone, bone in the thigh — the region of the lower limb between the hip and the knee. In many quadrupeds, four-legged animals the femur is the upper bone of the hindleg. The Femo ...
,
humerus The humerus (; : humeri) is a long bone in the arm that runs from the shoulder to the elbow. It connects the scapula and the two bones of the lower arm, the radius (bone), radius and ulna, and consists of three sections. The humeral upper extrem ...
,
vertebrae Each vertebra (: vertebrae) is an irregular bone with a complex structure composed of bone and some hyaline cartilage, that make up the vertebral column or spine, of vertebrates. The proportions of the vertebrae differ according to their spinal ...
,
maxilla In vertebrates, the maxilla (: maxillae ) is the upper fixed (not fixed in Neopterygii) bone of the jaw formed from the fusion of two maxillary bones. In humans, the upper jaw includes the hard palate in the front of the mouth. The two maxil ...
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 aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
'', a member of the normal
flora Flora (: floras or florae) is all the plant life present in a particular region or time, generally the naturally occurring (indigenous (ecology), indigenous) native plant, native plants. The corresponding term for animals is ''fauna'', and for f ...
found on the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
and
mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
s. In patients with sickle cell disease, the most common causative agent is ''
Salmonella ''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...
'', with a relative incidence more than twice that of S. aureus.


Diagnosis

The diagnosis of osteomyelitis is complex and relies on a combination of clinical suspicion and indirect laboratory markers such as a high white blood cell count and fever, although confirmation of clinical and laboratory suspicion with imaging is usually necessary. Radiographs and CT are the initial method of diagnosis, but are not sensitive and only moderately specific for the diagnosis. They can show the cortical destruction of advanced osteomyelitis, but can miss nascent or indolent diagnoses. Confirmation is most often by MRI. The presence of edema, diagnosed as increased signal on T2 sequences, is sensitive, but not specific, as edema can occur in reaction to adjacent
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
. Confirmation of bony marrow and cortical destruction by viewing the T1 sequences significantly increases specificity. The administration of intravenous gadolinium-based contrast enhances specificity further. In certain situations, such as severe Charcot arthropathy, diagnosis with MRI is still difficult. Similarly, it is limited in distinguishing avascular necrosis from osteomyelitis in
sickle cell anemia Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...
. Nuclear medicine scans can be a helpful adjunct to MRI in patients who have metallic hardware that limits or prevents effective magnetic resonance. Generally a triple phase technetium 99 based scan will show increased uptake on all three phases. Gallium scans are 100% sensitive for osteomyelitis but not specific, and may be helpful in patients with metallic prostheses. Combined WBC imaging with marrow studies has 90% accuracy in diagnosing osteomyelitis. Diagnosis of osteomyelitis is often based on radiologic results showing a
lytic The lytic cycle ( ) is one of the two cycles of viral reproduction (referring to bacterial viruses or bacteriophages), the other being the lysogenic cycle. The lytic cycle results in the destruction of the infected cell and its membrane. Bact ...
center with a ring of sclerosis.
Culture Culture ( ) is a concept that encompasses the social behavior, institutions, and Social norm, norms found in human societies, as well as the knowledge, beliefs, arts, laws, Social norm, customs, capabilities, Attitude (psychology), attitudes ...
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 cannot be trusted to produce reliable results. Factors that may commonly complicate osteomyelitis are fractures of the bone, amyloidosis, endocarditis, or
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
.


Classification

The definition of osteomyelitis (OM) is broad, and encompasses a wide variety of conditions. Traditionally, the length of time the infection has been present and whether there is suppuration ( pus formation) or osteosclerosis (pathological increased density of bone) are used to arbitrarily classify OM. Chronic OM is often defined as OM that has been present for more than one month. In reality, there are no distinct subtypes; instead, there is a spectrum of pathologic features that reflects a balance between the type and severity of the cause of the inflammation, the immune system, and local and systemic predisposing factors. * Suppurative osteomyelitis ** Acute suppurative osteomyelitis ** Chronic suppurative osteomyelitis *** Primary (no preceding phase) *** Secondary (follows an acute phase) * Non-suppurative osteomyelitis ** Diffuse sclerosing ** Focal sclerosing (
condensing osteitis Condensing osteitis, also known as focal sclerosing osteomyelitis, is a rare periapical inflammatory condition characterized by the formation of sclerotic bone near the roots of premolars and molars. This condition arises as a response to dental ...
) ** Proliferative periostitis ( periostitis ossificans, Garré's sclerosing osteomyelitis) ** Osteoradionecrosis OM can also be typed according to the area of the skeleton in which it is present. For example, osteomyelitis of the jaws is different in several respects from osteomyelitis present in a long bone. Vertebral osteomyelitis is another possible presentation.


Treatment

Osteomyelitis often requires prolonged
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
therapy for weeks or months. A PICC line or central venous catheter can be placed for long-term
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
medication administration. Some studies of children with acute osteomyelitis report that antibiotic by mouth may be justified due to PICC-related complications. It may require surgical debridement in severe cases, or even amputation. Antibiotics by mouth and by intravenous appear similar. Due to insufficient evidence it is unclear what the best antibiotic treatment is for osteomyelitis in people with sickle cell disease as of 2019. 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. Open surgery is needed for chronic osteomyelitis, whereby the involucrum is opened and the sequestrum is removed or sometimes saucerization can be done. Hyperbaric oxygen therapy has been shown to be a useful adjunct to the treatment of refractory osteomyelitis. Before the widespread availability and use of antibiotics, blow fly larvae were sometimes deliberately introduced to the wounds to feed on the infected material, effectively scouring them clean. There is tentative evidence that bioactive glass may also be useful in long bone infections. Support from randomized controlled trials, however, was not available as of 2015. Hemicorporectomy is performed in severe cases of Terminal Osteomyelitis in the Pelvis if further treatment won't stop the infection.


History

The word is from Greek words ὀστέον ''osteon'', meaning bone, μυελός ''myelos'' meaning marrow, and -ῖτις ''-itis'' meaning inflammation. In 1875, American artist
Thomas Eakins Thomas Cowperthwait Eakins (; July 25, 1844 – June 25, 1916) was an American Realism (visual arts), realist painter, photographer, sculptor, and fine arts educator. He is widely acknowledged to be one of the most important American artist ...
depicted a surgical procedure for osteomyelitis at Jefferson Medical College, in an
oil painting Oil painting is a painting method involving the procedure of painting with pigments combined with a drying oil as the Binder (material), binder. It has been the most common technique for artistic painting on canvas, wood panel, or oil on coppe ...
titled '' The Gross Clinic''. Canadian politician and premier of Saskatchewan
Tommy Douglas Thomas Clement Douglas (20 October 1904 – 24 February 1986) was a Scottish-born Canadian politician who served as the seventh premier of Saskatchewan from 1944 to 1961 and leader of the New Democratic Party from 1961 to 1971. A Bap ...
suffered from osteomyelitis as a child, and in 1910, underwent several surgeries, which the surgeon performed for free in exchange for allowing his medical students to observe the procedures (which Douglas's parents could not have otherwise afforded). This experience convinced him that medical care should be free for everyone. Douglas became known as the Canadian "Father of Medicare".


Fossil record

Evidence for osteomyelitis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. It has been reported in fossils of the large carnivorous dinosaur ''
Allosaurus fragilis ''Allosaurus'' ( ) is an extinct genus of theropoda, theropod dinosaur that lived 155 to 145 million years ago during the Late Jurassic Geologic time scale, period (Kimmeridgian to late Tithonian Geologic time scale, ages). The first fossil ...
''. Osteomyelitis has been also associated with the first evidence of parasites in dinosaur bones.


See also

* Brodie abscess * Chronic recurrent multifocal osteomyelitis * SAPHO syndrome * Garre's sclerosing osteomyelitis


References


External links

* {{Authority control Bacterial diseases Osteopathies Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate