Materiały źródłowe

• #1 Osteomyelitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK532250/

  Osteomyelitis is a serious infection of the bone that can be either acute or chronic. It is an inflammatory process involving the bone and its structures caused by pyogenic organisms that spread through the bloodstream, fractures, or surgery. […] Bone infection is called osteomyelitis. It is an acute or chronic inflammatory process involving the bone and its structures secondary to infection with pyogenic organisms, including bacteria, fungi, and mycobacteria. […] Healthy intact bone is resistant to infection. The bone becomes susceptible to disease with the introduction of a large inoculum of bacteria, from trauma, ischemia, or the presence of foreign bodies because bone sites to which microorganisms can bind are exposed. […] Certain bacteria such as Staphylococcus aureus adhere to the bone by expressing receptors, called adhesins, for some components of the bone matrix, including laminin, collagen, fibronectin, and bone sialoglycoprotein.

• #2 Osteomyelitis – Musculoskeletal and Connective Tissue Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/infections-of-joints-and-bones/osteomyelitis

  Osteomyelitis is inflammation and destruction of bone caused by bacteria, mycobacteria, or fungi. […] Osteomyelitis tends to occlude local blood vessels, which causes bone necrosis and local spread of infection. Infection may expand through the bone cortex and spread under the periosteum, with formation of subcutaneous abscesses that may drain spontaneously through the skin. […] If treatment of acute osteomyelitis is only partially successful, low-grade chronic osteomyelitis develops.

• #3 Osteomyelitis

  https://www.visualdx.com/visualdx/diagnosis/osteomyelitis?diagnosisId=52090&moduleId=101

  By definition, osteomyelitis involves a bacterial infection of bone tissue accompanied by destruction of bone tissue and the associated inflammatory response. Nonhematogenic infections can be either monomicrobial or polymicrobial, while hematogenic infections are usually monomicrobial as this type of osteomyelitis arises secondary to bacteremia. […] The exact pathophysiology will vary depending on the causative agent, but bacterial adherence and resistance to host defenses are some of the more important virulence factors of bacteria that are able to cause osteomyelitis. Additional features of pathogenesis include superlative infective processes and accompanying inflammatory features, vascular congestion / small vessel thrombosis, necrotic bone, and formation of new bone. Furthermore, the presence of polymorphonuclear leukocytes and other inflammatory cells plays an important role in the pathogenesis of the disease.

• #4 Osteomyelitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK532250/

  Bone can get infected via the hematogenous route of infection through bacteremic seeding of bone from a distant source of infection, contiguous spread from surrounding tissue and joints, or direct inoculation of bone from trauma or surgery. […] In patients with diabetes, osteomyelitis usually results from compromised blood supply to the lower extremities, which contributes to impaired local immunity and skin healing, promoting the spread of infection. […] Contiguous osteomyelitis frequently develops in debilitated patients who are wheelchair or bedbound and are predisposed to pressure-related skin ulcerations, especially in the sacrum, buttock, hips, and heel. […] The well-perfused metaphyses, which have scarce functioning phagocytes, are the most common site of infection in hematogenous osteomyelitis affecting the long bones.

• #5 Osteomyelitis: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/1000/p395.html

  Osteomyelitis is an inflammatory condition of bone secondary to an infectious process. […] Osteomyelitis is further classified by mechanism of infection as hematogenous or nonhematogenous. With hematogenous osteomyelitis, bacteria are seeded into bone secondary to a bloodstream infection and the condition is most common in children, older adults, and immunocompromised populations. […] Nonhematogenous osteomyelitis occurs from direct inoculation in the setting of surgery or trauma or with spread from contiguous soft tissue and joint infections. […] Methicillin-sensitive Staphylococcus aureus is the most frequently identified pathogen across all types of osteomyelitis, followed by Pseudomonas aeruginosa and methicillin-resistant S. aureus. […] Hematogenous osteomyelitis is often monomicrobial and can occur from aerobic gram-negative rods or from P. aeruginosa or Serratia marcescens in injection drug users.

• #6 Osteomyelitis – Wikipedia

  https://en.wikipedia.org/wiki/Osteomyelitis

  Osteomyelitis (OM) is the infectious inflammation of bone marrow. […] 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. […] 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), or penetrating trauma, including iatrogenic causes such as joint replacements or internal fixation of fractures, leading to a fracture-related infection, or secondary periapical periodontitis in teeth. […] Once the bone is infected, leukocytes enter the infected area, and, in their attempt to engulf the infectious organisms, release enzymes that lyse the bone. […] Chronic osteomyelitis may be due to the presence of intracellular bacteria. […] These combined factors may explain the chronicity and difficult eradication of this disease, resulting in significant costs and disability, potentially leading to amputation.

• #7 Osteomyelitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Osteomyelitis_pathophysiology

  Entry of the organism into bone is the first step in the development of osteomyelitis and occurs by three main mechanisms; hematogenous seeding, contiguous spread of infection to bone from adjacent soft tissue, and direct inoculation from trauma or orthopedic surgery (including prostheses). […] Several factors contributing to the pathogenesis of osteomyelitis include microbial factors and host factors. […] Etiologic pathogen possesses numerous cell-wall associated adhesins mediating specific attachment to a wide variety of extracellular matrix proteins found in bone including, fibronectin, laminin, osteopontin, bone matrix sialoprotein, and collagen. […] After attachment to the bone matrix, direct toxin effect of pathogen may lead to tissue necrosis. […] Adherent bacterial growth leads to the formation of a biofilm (an adherent consortium of micro-organisms enmeshed in an exocellular polysaccharide).

• #8 The imaging of osteomyelitis – Lee – Quantitative Imaging in Medicine and Surgery

  https://qims.amegroups.org/article/view/9839/html

  Osteomyelitis is inflammation of the bone marrow secondary to infection, which can progress to osteonecrosis, bone destruction and septic arthritis. An understanding of the pathogenesis of osteomyelitis is essential for recognition and interpretation of its imaging findings. Osteomyelitis arises from infection with a variety of microorganisms via different mechanisms. The progression of disease from acute to chronic stages produces a constellation of pathological features that can vary according to the age of the patient. Staphylococcus aureus is the causative organism in up to 80% of cases of osteomyelitis. Most of these cases involve community-acquired MRSA strains. One postulated cause for the increased severity of osteomyelitis in these patients is the production of a toxin known as Panto-Valentine leukocidin (PVL) by MRSA strains. It is important to be aware of an aseptic form of osteomyelitis known as chronic recurrent multifocal osteomyelitis (CRMO) that primarily affects children and adolescents. Blood cultures and bone biopsies in CRMO do not yield any microbial growth and there is no response to antibiotics. While the aetiology of CRMO has not been firmly established, an autoimmune cause has been postulated and there is a known association with inflammatory bowel disease. Three main routes for spread of osteomyelitis have been described; these are haematogenous, contiguous and direct inoculation. Blood-borne organisms, usually bacteria, are deposited in the medullary cavity and form a nidus of infection. In long bones, the region which is most predisposed to infection is the metaphysis, because it has a large supply of slow-flowing blood. The metaphysis is also prone to infection because there is discontinuity in the endothelial lining of the metaphyseal vessel walls. Infections originating from soft tissues and joints can spread contiguously to bone. This often occurs in the context of vascular insufficiency, such as in patients with diabetes mellitus or peripheral vascular disease. Direct seeding of bacteria into bone can occur as a result of open fractures, insertion of metallic implants or joint prostheses, human or animal bites and puncture wounds. Osteomyelitis can be divided into acute and chronic stages. The duration of disease determines what imaging findings are seen in osteomyelitis. The pathological features of chronic osteomyelitis are a result of osteonecrosis, caused by disruption of the intraosseous and periosteal blood supply during the acute stage of disease. A fragment of dead infected bone becomes separated from viable bone and is known as a sequestrum. The bacteria within the devascularised sequestrum are protected from antibiotics and the endogenous immune response, thus forming a nidus for chronic infection which may persist for many years. Haematogenous spread is the predominant mechanism of infection in children and usually causes long bone osteomyelitis. In adults, haematogenous spread is less common and when it does occur, usually leads to vertebral osteomyelitis. Adult osteomyelitis is most commonly caused by contiguous spread from soft tissue infections or direct inoculation. During skeletal maturation, there are changes in intraosseous vascular anatomy that determine the pattern of osteomyelitis spread in different age groups. In infants below 18 months of age, metaphyseal and epiphyseal vessels anastomose via transphyseal vessels that perforate the growth plate. These transphyseal vessels allow infection to spread from the metaphysis, where osteomyelitis commonly originates, to the growth plate, epiphysis and joint space. In children older than 18 months of age, the growth plate ossifies and forms a barrier between the metaphysis and epiphysis, limiting the spread of infection from the metaphysis. In adulthood, the growth plate is reabsorbed, removing the barrier between the metaphyseal and epiphyseal vessels. These vessels reanastomose, once again allowing spread of infection into the epiphysis and joint space. Subperiosteal abscesses are more common in children than in adults for two main reasons. In children, the cortical bone is thinner and more easily ruptured, leading to spread of infection from the medullary cavity to the subperiosteal space. The periosteum in children is also more loosely attached to the surface of the cortex and is easily separated, allowing accumulation of pus beneath the periosteal layer as a subperiosteal abscess.

• #9 Chronic osteomyelitis: what the surgeon needs to know in: EFORT Open Reviews Volume 1 Issue 5 (2016)

  https://eor.bioscientifica.com/view/journals/eor/1/5/2058-5241.1.000017.xml

  Chronic osteomyelitis represents a progressive inflammatory process caused by pathogens, resulting in bone destruction and sequestrum formation. […] The type of pathogen isolated is highly dependent on patient-related factors such as age, immune status, history of trauma and geographical location. […] Generally, haematogenous osteomyelitis is monomicrobic in nature, in contrast to contiguous-focus osteomyelitis that is polymicrobic. […] In adult chronic osteomyelitis, the most commonly involved pathogen is by far Staphylococcus aureus. […] Following the introduction of pathogens such as Staphylococcus aureus into the bone marrow cavity, regardless of the route of access, they adhere to membrane proteins such as fibronectin or collagen receptors, establishing an infection. […] Other microbial factors prevent access by host defences or penetration of the surrounding tissues.

• #10 Osteomyelitis: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/1348767-overview

  Bacteria may possess various factors that may contribute to the development of osteomyelitis. For example, factors promoted by S aureus may promote bacterial adherence, resistance to host defense mechanisms, and proteolytic activity. […] The metaphysis is the region of a long bone between the epiphysis and the diaphysis. This part contains the growth plate and, because of its vascular characteristics, is the preferred region of hematogenous osteomyelitis. In particular, children younger than 5 years are susceptible to it due to the abundance of blood vessels with leaky endothelium that end in capillary loops. […] As the bacteria continue to multiply, the scarce functioning phagocytes release enzymes that lyse the bone, thereby creating an inflammatory response. This results in formation of pus (a protein-rich exudate containing dead phagocytes, tissue debris, and microorganisms), increasing the intramedullary pressure in the area and thus further limiting the already compromised blood supply.

• #11 Osteomyelitis: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/785020-overview

  Bacteria may possess various factors that may contribute to the development of osteomyelitis. For example, factors promoted by S aureus may promote bacterial adherence, resistance to host defense mechanisms, and proteolytic activity. […] Bone infection may result from the treatment of trauma, which allows pathogens to enter bone and proliferate in the traumatized tissue. When bone infection persists for months, the resulting infection is referred to as chronic osteomyelitis and may be polymicrobial. Although all bones are subject to infection, the lower extremity is most commonly involved. […] As the bacteria continue to multiply, the scarce functioning phagocytes release enzymes that lyse the bone, thereby creating an inflammatory response. This results in formation of pus (a protein-rich exudate containing dead phagocytes, tissue debris, and microorganisms), increasing the intramedullary pressure in the area and thus further limiting the already compromised blood supply.

• #12 Skeletal infections: microbial pathogenesis, immunity and clinical management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8852989/

  Osteomyelitis remains one of the greatest risks in orthopaedic surgery. […] Important discoveries have uncovered novel mechanisms of S. aureus pathogenesis and persistence within bone tissue, including implant-associated biofilms, abscesses and invasion of the osteocyte lacuno-canalicular network. […] In this Review, we summarize recently described mechanisms of S. aureus osteomyelitis pathogenesis, including intracellular infection, staphylococcal abscess communities (SACs) and invasion of the osteocyte lacuno-canalicular network (OLCN). […] S. aureus is specifically pathogenic in skeletal infections because of its unique ability to invade, colonize and thrive within bone. […] Key mechanisms for S. aureus persistence in skeletal infections are outlined in Fig. 2. […] Staphylococcus aureus employs a variety of pathogenic mechanisms during skeletal infection.

• #13 Skeletal infections: microbial pathogenesis, immunity and clinical management | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00686-0

  Osteomyelitis remains one of the greatest risks in orthopaedic surgery. […] Important discoveries have uncovered novel mechanisms of Staphylococcus aureus pathogenesis and persistence within bone tissue, including implant-associated biofilms, abscesses and invasion of the osteocyte lacuno-canalicular network. […] In this Review, we discuss the mechanisms of persistence and immune evasion in Staphylococcus aureus infection of the skeletal system as well as features of other osteomyelitis-causing pathogens in implant-associated and native bone infections. […] We also describe how the host fails to eradicate bacterial bone infections, and how this new information may lead to the development of novel interventions.

• #14 Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy” | Bone Research

  https://www.nature.com/articles/s41413-019-0061-z

  Osteomyelitis is a devastating disease caused by microbial infection of bone. […] Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. […] Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone. […] In contrast, S. aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. […] Thus, the goal of this review is to highlight these potential breakthroughs, which challenge the scientific premise of established paradigms, including acute and chronic osteomyelitis, intracellular infection of bone cells, and the efficacy of antibiotic-laden bone cement.

• #15 Skeletal infections: microbial pathogenesis, immunity and clinical management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8852989/

  S. aureus invasion of the osteocyte-lacuno canalicular network (OLCN), most commonly within a sequestrum, permits evasion of host immune cells during osteomyelitis and requires S. aureus deformation to invade canaliculi of bone. […] An important and well-studied mechanism for S. aureus pathogenesis in osteomyelitis is the formation of biofilms, which has been extensively reviewed. […] The presence of SACs at the site of a bone infection is often used to diagnose and/or classify the stage of osteomyelitis as SACs can greatly increase the severity of infections by restricting blood flow to the area. […] The formation of SACs represents an effective manipulation of the host response to prolonged S. aureus survival within soft tissues. […] S. aureus first enables the formation of a protective fibrous pseudocapsule through the activity of coagulase (CoA) and von Willebrand factor-binding protein (vWbp), which bind prothrombin to activate its conversion of fibrinogen into fibrin.

• #16 The pathophysiology of chronic osteomyelitis

  http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S1681-150X2013000500002

  Biofilm formation occurs in five stages, namely adhesion, production of the extra-cellular matrix, colonisation, maturation and finally dispersion of bacteria. […] Antibiotics face mechanical and osmotic challenges in penetrating a biofilm, while the reduced growth rate of bacteria due to incomplete penetration of metabolic substrates and accumulation of waste product, makes the biofilm-based bacteria even more resilient. […] The innate immune response is critical in the early phase of bacterial colonisation. It is triggered at the site of bacterial infection by the production of cytokines like interleukin-1 (IL-1), IL-6 and tumour necrosis factor (TNF). […] Acquired or adaptive immunity is responsible for the eradication of chronic or persistent infections and also plays an important role in the prevention of recurrence.

• #17 SciELO Brazil – Osteomyelitis: an overview of antimicrobial therapy Osteomyelitis: an overview of antimicrobial therapy

  https://www.scielo.br/j/bjps/a/9QfKdN4zxTjncQDwh5BGpcv/

  Osteomyelitis is an inflammatory bone disorder caused by infection, leading to necrosis and destruction of bone. […] Treatment of osteomyelitis is challenging particularly when complex multiresistant bacterial biofilm has already been established. Bacteria in biofilm persist in a low metabolic phase, causing persistent infection due to increased resistance to antibiotics. […] The pathophysiology of osteomyelitis is multifactorial and begins with spread of the organism. Bacteria may reach the bone by hematogenous seeding, direct inoculation, or airborne contamination. […] Once an organism reaches the bone it causes acute inflammation. […] Microorganisms avoid the host defenses and antibiotics through a multiplicity of mechanisms including surviving in a dormant state inside osteoblasts, developing a biofilm, and acquiring a very slow metabolic rate.

• #18 Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy” | Bone Research

  https://www.nature.com/articles/s41413-019-0061-z

  These data are consistent with the conclusions from the 2018 International Consensus Meeting on Musculoskeletal Infection, which found that the incidences of infection for all orthopedic subspecialties range from 0.1% to 30%, at a cost of $17 000$150 000 per patient. […] An astounding 75% of osteomyelitis cases are caused by pathogens of the Staphylococcus genus. […] The invasive success of S. aureus infection can be attributed to its arsenal of virulence factors and resistance mechanisms including secreted toxins, adherence as a means of immune evasion, biofilm formation, the creation of slow growing small colony variant (SCV) subpopulations, and the development of antimicrobial resistance. […] Biofilm formation occurs in four generalized stages including: (1) bacterial cell attachment, (2) proliferation, (3) biofilm maturation, and (4) detachment.

• #19 Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy” | Bone Research

  https://www.nature.com/articles/s41413-019-0061-z

  Biofilms confer long-term bacterial cell survival in hostile environments by a variety of mechanisms. […] Taken together, biofilm presents a significant concern to surgeons when treating implant-associated infections. […] The third and most recently discovered reservoir of bacteria in chronic osteomyelitis is S. aureus colonization of the OLCN. […] These observations suggest that S. aureus may be able to survive for decades within the OLCN with an inexhaustible supply of nutrients, while evading immune attack. […] Collectively, these novel findings suggest that invasion and propagation within the immune-privileged OLCN is a pathogenic mechanism that renders S. aureus infection of bone incurable. […] The role of intracellular persistence in chronic osteomyelitis disease pathology remains a subject of intense debate because of a lack of compelling in vivo evidence.

• #20 Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

  https://www.mdpi.com/2072-6651/12/8/516

  The accessory gene regulator (Agr) system is a key mediator of bacterial responses to environmental stimuli and regulates the production of many S. aureus factors to promote bacterial survival and dissemination. […] The capability of S. aureus to grow in a multitude of host tissues, including bone, suggests remarkable flexibility in responding to heterogeneous host immune responses and local nutrient availability. […] The production of bacterial toxins has less favorable tradeoffs, including an increased energy requirement and the potential to incite host immune defenses and increase inflammation. […] The Agr two-component system is responsible for controlling critical toxin genes involved in S. aureus pathogenesis, including hemolysins and phenol-soluble modulins (PSMs), while also repressing production of proteins involved in bacterial adherence and aggregation, such as coagulase (Coa) and von Willebrand factor-binding protein (vWbp).

• #21 Skeletal infections: microbial pathogenesis, immunity and clinical management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8852989/

  S. aureus utilizes the iron-scavenging proteins IsdA, IsdB and IsdH to bind haemoglobin to extract haem as a source of iron. […] Ultimately, the only effective means of eradication is abscess disruption or debridement. […] Skeletal infections also involve bacteria existing as persister cells and as SCVs, which can arise due to environmental triggers such as oxidative stress, nutrient limitation, intracellular residence and low pH. […] The immune system plays a crucial role in the defence against skeletal infections and maintaining bone homeostasis. […] The ability of S. aureus to survive long-term in the bone niche is attributed to the expression of an array of virulence factors, including adhesins, immunomodulatory proteins, toxins and superantigens with redundant functions. […] Virulence proteins enable Staphylococcus aureus to successfully evade host immune responses.

• #22 Osteomyelitis 2 – OrthoPaedia

  https://www.orthopaedia.com/osteomyelitis-2/

  Osteomyelitis is an infection of the bone caused by bacteria, fungi, or mycobacteria. The infection can land in the bone via the bloodstream (hematogenous spread), contiguous spread from adjacent soft tissues, or direct inoculation during trauma, or surgery. The disease process is characterized by the progressive destruction of bone at the center of infection and new appositional bone growth around it. […] When bacterial seeding occurs, regardless of mechanism, a local immune response leads to increased vascular permeability, edema, and recruitment of polymorphonuclear leukocytes. This purulence increases pressure within the medullary canal and can further obstruct blood flow. Extrusion of purulent fluid through the bone’s surface to the periosteum, resulting in a sub-periosteal abscess, can occur as well. Increased pressure leads to ischemia and bone necrosis. The necrotic and infected bone may become sequestered during the formation of new bone, making the eradication of bacteria difficult or impossible without surgical excision. The new bone is called an “involucrum,” and the infected bone it surrounds is called the “sequestrum.”

• #23 Osteomyelitis: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/1348767-overview

  The infection and the formation of pus in this region strip the periosteum from the shaft and stimulate an osteoblastic response. As a result, new bone is formed in response to the periosteal stripping. Part of the necrotic bone may separate; this is referred to as the sequestra. […] In a severe infection, the entire shaft is encased in a sheath of new bone, which is referred to as the involucrum. Once this occurs, a major part of the shaft has been deprived of its blood supply. The involucrum can have openings called cloacae, which allow pus to escape from the bone, leading to fulminant disease. […] In the 0- to 18-month age range, the epiphysis and the metaphysis have communicating vessels that result in direct extension of infection from metaphysis to epiphysis. Once the infection extends into the epiphysis, it leads to destruction of the epiphyseal cartilage and secondary ossification center, resulting in permanent growth impairment. The extension into the epiphysis also leads to a higher incidence of septic arthritis.

• #24 Osteomyelitis: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/785020-overview

  The infection and the formation of pus in this region strip the periosteum from the shaft and stimulate an osteoblastic response. As a result, new bone is formed in response to the periosteal stripping. Part of the necrotic bone may separate; this is referred to as the sequestra. […] In a severe infection, the entire shaft is encased in a sheath of new bone, which is referred to as the involucrum. Once this occurs, a major part of the shaft has been deprived of its blood supply. The involucrum can have openings called cloacae, which allow pus to escape from the bone, leading to fulminant disease. […] The extension into the epiphysis also leads to a higher incidence of septic arthritis.

• #25 Osteomyelitis – TeachMeSurgery

  https://teachmesurgery.com/orthopaedic/principles/osteomyelitis/

  Once bacteria enter the bone tissue, they express adhesins to bind to the host tissue proteins and produce a polysaccharide extracellular matrix. Through this, the pathogens are able propagate, spread, and seed further in the tissue. […] In chronic cases, the infection can lead to devascularisation of the affected bone, resulting in necrosis and resorption of the surrounding bone. This leads to a floating piece of dead bone, termed a sequestrum, which acts as a reservoir for infection (and cannot be penetrated by antibiotics, as it is avascular). […] An involucrum can also form, following the sequestrum formation, whereby the region becomes encased in a thick sheath of new periosteal bone.

• #26 The pathophysiology of chronic osteomyelitis

  http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S1681-150X2013000500002

  Chronic osteomyelitis is characterised by osteolysis in combination with reparative osteosclerosis, which aims to confine the inflammatory process. […] The physiological status of the host determines not only the clinical extent of the disease, but also the treating physician’s ability to effect cure.

• #27 Recommendations for the treatment of osteomyelitis | The Brazilian Journal of Infectious Diseases

  https://www.bjid.org.br/en-recommendations-for-treatment-osteomyelitis-articulo-S1413867014000579

  With the advances in surgical treatment, antibiotic therapy, and the current resources for accurate diagnosis and differentiated approaches to each type of osteomyelitis, better results are being obtained in the treatment of this disease. […] Osteomyelitis can be defined as an inflammation of the bone tissue caused by an infectious agent. This infection may be hematogenic, contiguous to an adjacent infectious focus, or even the result of direct bacterial inoculation from a traumatic mechanism. […] Hematogenous osteomyelitis has more consolidated data in the medical literature, and is considered a predominantly pediatric disease, with 85% of patients aged below 17 years. […] Chronic osteomyelitis represents a major health problem due to its significant morbidity and low mortality rate.

• #28 Osteomyelitis and Other Bone and Joint Infections | Obgyn Key

  https://obgynkey.com/osteomyelitis-and-other-bone-and-joint-infections/

  Transphyseal vessels in children younger than 18 months of age can lead to spread of the infection from the metaphysis into the epiphysis and joint space, causing a secondary septic arthritis. The growth plate, after it has formed, serves as a barrier to extension of infection into the epiphysis and joint.

• #29 Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

  https://www.mdpi.com/2072-6651/12/8/516

  Staphylococcus aureus is a Gram-positive pathogen capable of infecting nearly every vertebrate organ. Among these tissues, invasive infection of bone (osteomyelitis) is particularly common and induces high morbidity. Treatment of osteomyelitis is notoriously difficult and often requires debridement of diseased bone in conjunction with prolonged antibiotic treatment to resolve infection. During osteomyelitis, S. aureus forms characteristic multicellular microcolonies in distinct niches within bone. Virulence and metabolic responses within these multicellular microcolonies are coordinated, in part, by quorum sensing via the accessory gene regulator (agr) locus, which allows staphylococcal populations to produce toxins and adapt in response to bacterial density. During osteomyelitis, the Agr system significantly contributes to dysregulation of skeletal homeostasis and disease severity but may also paradoxically inhibit persistence in the host.

• #30 Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

  https://www.mdpi.com/2072-6651/12/8/516

  While Agr only responds to AIP concentration, multiple environmental cues, including oxygen concentration, oxidative stress, and nutrient availability, influence S. aureus toxin production. […] Bone has relatively lower physioxia than many tissues and becomes increasingly hypoxic over the course of infection. […] S. aureus responds to immune and nutrient stress in part by secreting virulence factors, including enzymes that degrade host tissues, cytolytic toxins that target host cells, and molecules that incapacitate immune defenses. […] The Agr regulatory system can control the production of toxins and other virulence factors through direct gene activation/repression by AgrA or RNAIII, translational control through RNAIII base pairing with mRNA, and via RNAIII mRNA duplex formation that promotes endonuclease activity for mRNA degradation. […] Agr-mediated regulation of bacterial toxins and factors associated with persistence has been implicated in the pathogenesis of S. aureus osteomyelitis in a number of studies.

• #31 Pathogenesis of osteomyelitis – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-osteomyelitis

  Pathogenesis of osteomyelitis […] Osteomyelitis is an infection involving bone. […] The pathogenesis and pathology of osteomyelitis will be reviewed here. […] Osteomyelitis may be divided into two major categories based upon the pathogenesis of infection: (1) hematogenous osteomyelitis and (2) nonhematogenous osteomyelitis, which develops adjacent to a contiguous focus of infection or via direct inoculation of infection into the bone. […] Either hematogenous or contiguous-focus osteomyelitis can be classified as acute or chronic. […] Acute osteomyelitis evolves over several days to weeks and can progress to a chronic infection. […] The hallmark of chronic osteomyelitis is the presence of dead bone (sequestrum). […] Other common features of chronic osteomyelitis include involucrum (reactive bony encasement of the sequestrum), local bone loss, and, if there is extension through cortical bone, sinus tracts.

• #32 Pathogenesis of osteomyelitis – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-osteomyelitis/print

  Pathogenesis of osteomyelitis. Osteomyelitis is an infection involving bone. The pathogenesis and pathology of osteomyelitis will be reviewed here. Osteomyelitis may be divided into two major categories based upon the pathogenesis of infection: (1) hematogenous osteomyelitis and (2) nonhematogenous osteomyelitis, which develops adjacent to a contiguous focus of infection or via direct inoculation of infection into the bone. Either hematogenous or contiguous-focus osteomyelitis can be classified as acute or chronic. Acute osteomyelitis evolves over several days to weeks and can progress to a chronic infection. The hallmark of chronic osteomyelitis is the presence of dead bone (sequestrum). Other common features of chronic osteomyelitis include involucrum (reactive bony encasement of the sequestrum), local bone loss, and, if there is extension through cortical bone, sinus tracts.

• #33 Pathogenesis of osteomyelitis – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-osteomyelitis

  Brodie abscess is a form of subacute osteomyelitis that is usually hematogenous in origin but can occur as a the result of trauma; the classic presentation of Brodie abscess consists of a cavity filled with suppurative and/or granulation in a long bone metaphysis, surrounded by dense fibrous tissue and sclerotic bone.

• #34 Pathogenesis of osteomyelitis – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-osteomyelitis/print

  Brodie abscess is a form of subacute osteomyelitis that is usually hematogenous in origin but can occur as a the result of trauma; the classic presentation of Brodie abscess consists of a cavity filled with suppurative and/or granulation in a long bone metaphysis, surrounded by dense fibrous tissue and sclerotic bone.

• #35 Osteomyelitis – Infectious Disease Advisor

  https://www.infectiousdiseaseadvisor.com/ddi/osteomyelitis/

  Osteomyelitis is acute or chronic inflammation of bone tissue due to infection with bacteria or fungi. It often occurs as a result of bacteremia (bacterial infection in the bloodstream) or sepsis, which spreads to the bone. […] Osteomyelitis occurs when inflammation, trauma, or ischemia compromises the integrity of the bone, allowing microorganisms to bind to damaged bone tissue. […] Trauma and/or inflammation may cause bone tissue, including bone marrow, to be susceptible to infection with certain microorganisms. Osteomyelitis can be caused by a single species of bacteria or fungi; alternatively, it may be caused by multiple organisms. […] Histopathologic examination of osteomyelitis is used to determine whether disease is acute or chronic. Acute osteomyelitis pathologic specimens show microorganisms, congested or thrombosed blood vessels, and a neutrophilic infiltrate. Chronic osteomyelitis is marked by necrotic bone, as well as a mononuclear infiltrate, granulation tissue, bone loss, and sinus tract formation.

• #36

  https://www.orthobullets.com/trauma/1057/osteomyelitis–adult

  Osteomyelitis is the infection of bone characterized by progressive inflammatory destruction and apposition of new bone. […] Diagnosis requires careful assessment of radiographs, MRI and determining the organism via biopsy and cultures. […] Treatment is often a combination of culture-directed antibiotics and surgical debridement of nonviable tissue. […] mechanism of spread […] hematogenous […] originated or transported by blood […] may be due to bacterial or viral systemic illness. […] most common etiology in children. […] vertebrae are the most common hematogenous site in adults. […] S. aureus is the most common organism. […] contiguous-spread […] associated with previous surgery, trauma, wounds, or poor vascularity. […] can be bacterial (most common), mycobacterial, or fungal in nature.

• #37 Osteomyelitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Osteomyelitis_pathophysiology

  Biofilm pathogens are more resistant to host defense and are able to survive longer than usual. […] Pathogens trigger inflammation and due to this inflammatory process, intraosseous pressure inside the tight bone matrix increases and may lead to thrombosis of bone vasculature that finally results in bone death. […] If the infection progresses, pus may track to other areas of the bone along the medullary canal or through the Haversian systems in cortical bone from the medulla to the outer surface of the cortex and form a subperiosteal abscess. […] Dead bone accelerates biofilm formation. […] Both the inflammatory cytokines and mediators released during infection, and in some cases bacterial products themselves, can trigger bone resorption either by osteoclast activation or by stimulating phagocytic cells to take on a bone-resorbing phenotype.

• #38 Osteomyelitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Osteomyelitis_pathophysiology

  Bone loss starts around the dead area, resulting in the separation of the dead area of bone from the surrounding living bone, ultimately, forming the Sequestrum. […] When periosteal stripping occurs, the resulting periosteal reaction produces a shell of new bone; the Involucrum, around the dead bone.

• #39 Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy” | Bone Research

  https://www.nature.com/articles/s41413-019-0061-z

  Throughout all in vivo studies, we failed to identify intracellularly infected live bone cells. […] In contrast, we routinely observed intracellular infection of leukocytes, so called Trojan Horses, in septic animals and patients. […] The current research on intracellular persistence of S. aureus in osteomyelitis in vivo is still very limited. […] The discovery of OLCN invasion is particularly concerning for the treatment of implant-associated osteomyelitis, because it is impossible to know if all segments of infected bone have been completely debrided.

• #40 Recessive Coding and Regulatory Mutations in FBLIM1 Underlie the Pathogenesis of Sterile Osteomyelitis – ACR Meeting Abstracts

  https://acrabstracts.org/abstract/recessive-coding-and-regulatory-mutations-in-fblim1-underlie-the-pathogenesis-of-sterile-osteomyelitis/

  Recessive Coding and Regulatory Mutations in FBLIM1 Underlie the Pathogenesis of Sterile Osteomyelitis […] Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There is evidence for a genetic basis in several syndromic forms of the disease including the Deficiency of the Interleukin-1 Receptor Antagonist (DIRA; due to mutations in IL1RN), Majeed syndrome (due to mutations in LPIN2) and murine chronic multifocal osteomyelitis (due to mutations in Pstpip2). However, for the majority of cases of CRMO, the genetic basis remains unknown. […] Via whole-exome sequencing, we detected a homozygous mutation in the filamin-binding domain of FBLIM1 in an affected child with consanguineous parents. Microarray analysis of bone marrow macrophages from the CRMO murine model (cmo mouse) determined that the Fblim1 ortholog is the most differentially expressed gene, further implicating it in disease pathogenesis. In addition, studies suggest FBLIM1/FBLP1 is an anti-inflammatory molecule regulated by STAT3, and one involved in bone remodeling via ERK1/2 phosphorylation and the subsequent regulation of RANKL activation. […] Our data implicate FBLIM1 in the pathogenesis of CRMO and autoinflammatory disease.

• #41 Chronic Recurrent Multifocal Osteomyelitis (CRMO): Pathogenesis,

  https://www.longdom.org/open-access/chronic-recurrent-multifocal-osteomyelitis-crmo-pathogenesis-clinical-features-diagnostic-approaches-and-management-considerations-107684.html

  Chronic Recurrent Multifocal Osteomyelitis (CRMO) is an autoimmune inflammatory disease with recurrent bone lesions. […] The origin of the disease has been proposed to be auto-inflammatory, given the idiopathic nature of the disease, its association with other autoimmune diseases, and the absence of alterations in lymphocytes or antibodies. […] The pathophysiology of the disease is also unknown. Monocytes from CRMO patients show reduced production of Interleukin-10 (IL-10), which triggers inflammasome activation and an imbalance of pro-inflammatory cytokines (IL-12, TNF-, IL-20, IL-6) over anti-inflammatory cytokines (IL-10, IL-19, IL-1RN), leading to osteoclast activation and bone inflammation. […] CRMO is a rare, low prevalence entity with an uncertain pathophysiology based on a regulatory and pro-inflammatory cytokine imbalance.

• #42

  https://link.springer.com/article/10.1007/s11908-999-0028-0

  Despite significant progress in antibiotic therapy and orthopedic surgery, osteomyelitis remains a difficult-to-treat infection that is often associated with recurrence. […] In this paper we summarize the most recent developments in understanding the pathogenesis of this complex disease, as well as novel means for its diagnosis and treatment.

• #43 The Many Faces of Osteomyelitis: A Pictorial Review | Journal of the Belgian Society of Radiology

  https://jbsr.be/articles/10.5334/jbr-btr.1300

  This manuscript will mainly focus on hematogeneous spread of osteomyelitis. […] The nature of blood supply to the diaphysis, metaphysis and epiphysis depends on the age of the patient. […] Thorough knowledge of these different patterns allows an understanding of the different radiological patterns of OM between children and adults. […] Although traditionally the growth plate has been considered a barrier for epiphyseal extension of the infectious focus in children because of the specific age-dependent vascularization, this barrier has been shown permeable on magnetic resonance imaging (MRI), as this technique is more sensitive to demonstrate subtle marrow changes as an early sign of infectious spread across the growth plate. […] The variable imaging appearance of osteomyelitis may be explained by the different pathogenic mechanisms involved in the spread of the infection and by the age-related vascularization of bone.

• #44 Osteomyelitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK532250/

  The main histopathological finding in acute osteomyelitis are microorganisms, congested or thrombosed blood vessels, and infiltrates of neutrophils. […] The categorization of osteomyelitis as acute or chronic is based on the histopathological findings rather than the duration of illness. […] Effective treatment of osteomyelitis involves a collaborative effort among various medical and surgical specialties. The two main aspects of therapy are surgical containment of the infection and prolonged antibiotics. […] Prolonged antibiotic therapy is the cornerstone of treatment for osteomyelitis. Results of culture and sensitivity should guide antibiotic treatment if possible, but in the absence of this data, it is reasonable to start empiric antibiotics. […] The recommended duration of treatment for osteomyelitis in adults is 4 to 6 weeks of parenteral antibiotic therapy to achieve acceptable cure rates with a decreased risk of recurrence.

• #45

  https://journals.lww.com/co-infectiousdiseases/fulltext/2015/06000/current_concepts_in_pathogenesis_of_acute_and.8.aspx

  Although microbial invasion is responsible to be the cause for inflammatory bone disorders, except for an autoinflammatory origin, the underlying and detailed mechanisms in the pathogenesis of osteomyelitis are not yet fully understood, but represent an absolute precondition for the development of effective causal treatment strategies in the future.

• #46 Infection and Drug Resistance – Dove Press Open Access Publisher | Advances in Osteomyelitis: Pathogenesis, Diagnosis, and Treatment

  https://www.dovepress.com/infection-and-drug-resistance-archive28-collection141

  Osteomyelitis (OM) refers to osseous tissue infection, with or without surrounding soft tissue infection. It is characterized by inflammatory associated bone destruction, with or without new bone formation. […] On the one hand, the pathogenesis of this disorder is still not fully understood. […] This Article Collection contains original research articles covering the current concepts and investigations regarding the pathogenesis, diagnosis, and treatment of osteomyelitis.

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