5 Osteomyelitis

Martin McNally

Osteomyelitis is a fascinating condition that can affect all parts of the human skeleton. It presents in several distinct ways, but all have varying degrees of inflammation, systemic ill health, bone death, and soft-tissue compromise. Understanding the components of the disease and the interplay between bacteria, biofilm formation, and the host response is critical to successful treatment. Recent advances in diagnostic methods, imaging, local delivery of antimicrobials, and bone reconstruction have greatly improved the outcome for many patients. Surgery remains central to the effective treatment of chronic osteomyelitis and many acute cases. Eradication of infection is largely dependent on the skill of the surgeon in identifying the areas of dead bone and removing them during surgery. Osteomyelitis is challenging and rewarding to treat, and most patients should enjoy prolonged disease-free periods or cure. Holistic care of the patient requires close collaborative working in a multidisciplinary team including physicians, surgeons, nurses, and therapists to achieve the best outcomes.

Osteomyelitis – fracture-related infection – diagnosis – surgical treatment – local antibiotics – classification

5 Osteomyelitis

Practical Tips

Accurate diagnosis is the starting point for successful treatment. Preoperative investigations and tissue sampling should be completed with a standardized protocol and sterile equipment.
In most cases, there is no urgency for treatment. Patients can be assessed, optimized, and treatment carefully planned over several weeks.
Acute osteomyelitis can often be treated with antibiotics alone, if it is diagnosed early and the patient does not deteriorate.
Chronic infection always requires surgery with targeted antimicrobial therapy for eradication. Single-stage surgery is possible for many patients.
Surgical excision of dead bone needs experience and an understanding of the patterns of the disease.

5.1 Introduction

Osteomyelitis has been present on the earth since the development of bone tissue. It has been identified in dinosaur bones from the Jurassic period (▶ Fig. 5.1) and is widely reported in classical medical writings in Greek and Roman literature. ¹ Native bone infection remains common worldwide, but the epidemiology is changing. In the developed world, bone infections arising from surgical intervention, injury, peripheral vascular disease, and as sequelae of diabetes mellitus are now more frequent than hematogenous osteomyelitis. Intravenous (IV) drug abuse and being immunocompromised (from human immunodeficiency virus [HIV] and cytotoxic therapy) are now major risk factors. ² ^, ³

**Fig. 5.1 (a, b)** This fibula of a 65-million-year-old tyrannosaur exhibits all of the features of established chronic osteomyelitis in the diaphysis. The dinosaur must have survived the infection for many months or years to develop the mature involucrum and extensive sinuses present on the fibula. (© Field Museum [2018], Chicago.)

In the past, bone infection was limb or life threatening without appropriate treatment. A study of acute hematogenous osteomyelitis in Glasgow, United Kingdom (UK), reported a 33% mortality between 1936 and 1940, but this fell to under 10% after 1941, with better use of early surgery and antibiotics. ⁴ Now, infection often presents more insidiously, with less specific symptoms and gradual bone destruction, in the absence of systemic features. The gradual evolution of the chronic disease causes irreversible changes in tissues, particularly around bone, that can result in loss of function and make successful treatment difficult.

The introduction of antimicrobial therapy 80 years ago has greatly improved the outcome for patients with severe systemic infections, but there are very few occasions when bone infection can be effectively treated by antimicrobials alone. In most cases, a good outcome depends on carefully planned and executed surgery with adjunctive antibiotics.

5.2 Terminology

There are several clinical scenarios that merit a clear definition, as they affect patients differently and require modification of treatment.

Osteomyelitis is an inflammatory condition of cortical and medullary bone caused by an infecting organism, usually limited to a single bone but can be multifocal.

Hematogenous osteomyelitis arises from the spread of bacteria in the blood (bacteremia). This is unusual, as healthy bone is very resistant to bacteria, and it is difficult to induce osteomyelitis experimentally without causing bone death or without using a very large bacterial inoculation. The infection begins in the medulla but can rapidly spread to involve the cortex with fistulation, subperiosteal abscess formation, and soft-tissue extension. In young children, the infection may fistulate to the adjacent joint and present as septic arthritis.

Acute osteomyelitis may be defined as a bone infection presenting within the first 2 weeks of symptom onset. It occurs in approximately 5 per 100,000 children per year, with males twice as likely to be affected. ⁵ The most common site is the metaphysis of the lower limb bones; infection in other sites is associated with delayed diagnosis and worse outcome. ⁵ Initially, acute osteomyelitis affects living bone, but progression leads to bone death, which signals the onset of chronic infection.

Brodie’s abscess is a medullary, hematogenous osteomyelitis with a subacute presentation, first described by Sir Benjamin Brodie in 1845. ⁵ The central bone abscess is often surrounded by dense new bone (medullary involucrum), which potentially prevents sinus formation (▶ Fig. 5.2).

**Fig. 5.2 (a)** Radiograph and **(b)** magnetic resonance imaging (MRI) of a Brodie’s abscess. This subacute form of osteomyelitis is medullary with dense new bone formation around the central nidus. Over time, the bone may become expanded, as seen in this case.

Contiguous osteomyelitis occurs when bacteria invade the bone from an adjacent infective focus. It is the most common type of bone infection in adults, usually following an open fracture, an orthopaedic operation, or skin breakdown. Patients with contiguous osteomyelitis often have other medical conditions (e.g., diabetes with foot ulcers, paraplegia with pressure sores, and peripheral arterial or venous insufficiency with ulceration) that require treatment alongside the bone infection.

Fracture-related infection (FRI) describes contiguous osteomyelitis following an open fracture or internal fixation of closed fractures. ⁷

Chronic osteomyelitis may begin as acute hematogenous or contiguous disease. In 1984, George Cierny and Jon Mader described the condition in the statement: “The hallmark of chronic osteomyelitis is infected, dead bone within a compromised soft-tissue envelope.” ⁸ This important summary highlights the features that contribute to chronicity that need to be addressed in treatment. The combination of subperiosteal abscess formation, medullary ischemia with intravascular thrombosis, and activation of inflammatory cells all contribute to bone death. Dead bone fragments may separate from living bone tissue (sequestration) and if they are small, they can be absorbed or move to the surface along sinus tracts. Discharge of these sequestra may arrest the progression of the infection and allow the limb to heal. However, residual dead bone and bacterial colonization within the bone will often lead to recurrence (▶ Fig. 5.3).

**Fig. 5.3** Pathology of osteomyelitis, illustrating the progression from acute to chronic infection, with bone death, sequestration, and sinus formation. (Reproduced from McNally MA, Berendt AR. Osteomyelitis. In: Firth J, Conlon C, Cox T, eds. Oxford Textbook of Medicine. 6th edition. Oxford, United Kingdom: Oxford University Press; 2020:4688–4695 with permission from Oxford University Press.)

Large sequestra remain trapped within a surrounding layer of new bone formation (involucrum) (▶ Fig. 5.4). Bacteria attach to bone through interactions between bacterial adhesins and host proteins. Adherent bacteria divide and, together with the host cells, produce an extracellular polysaccharide matrix (biofilm), leading to chronicity. Additionally, intracellular survival within osteoblasts and macrophages can occur, particularly in Staphylococcus aureus infections. ⁹

**Fig. 5.4** After 6 weeks of the onset of hematogenous osteomyelitis. The peripheral new bone (involucrum) has developed and the central dead bone has separated (sequestrum, *black arrow*). The involucrum is well vascularized and will eventually reform a new humeral diaphysis (*white arrow*).

Reactivation of infection may occur over many years, with discharge of pus from cutaneous sinuses and further bone death. Long-term drainage from sinuses prevents systemic ill-health, but risks the development of squamous carcinoma (Marjolijn’s ulcer) in the wall of a chronic active sinus.

Chronic sclerosing osteomyelitis (of Garré) is a rare form of osteomyelitis mainly affecting the tibia or clavicle. It presents with pain, but does not form draining sinuses. It has a typically dense, sclerotic appearance on X-ray and is invariably culture-negative. It may affect more than one bone when it is also known as chronic relapsing multifocal osteomyelitis (CRMO). It may be associated with SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis). ¹⁰ Many rheumatologists now believe it is an autoimmune condition and not an infective disorder. In the past, it was regarded as a benign condition that was self-limiting in adult life, but pain may persist for many years.

5.3 Classification

Osteomyelitis can be classified by the onset of symptoms (acute or chronic), the source of the infection (hematogenous or contiguous focus), or the cultured organism. These characteristics can be difficult to determine and are not often helpful in designing treatment regimens or predicting outcome.

The Cierny and Mader classification defines the features of infection in the bone (four anatomic stages) and relates this to the physiological condition of the patient.

Three “host groups” (A, no active concurrent disease; B, compromised host; C, severe comorbidity preventing surgery) are described. Group B patients, with conditions that compromise wound healing, reduce the efficacy or tolerance of drug therapy, or prevent effective surgery, have worse outcomes compared to healthy uncompromised hosts (▶ Table 5.1).

**Table 5.1** The Cierny and Mader classification defines a group of patients (Group B hosts) who have conditions which will adversely affect the treatment options or outcome after surgery
Conditions which compromise the treatment of osteomyelitis
Local factors in the limb (B_l-host)	Systemic factors (B_s-host)
Arterial ischemia Venous insufficiency Previous surgery DVT Lymphoedema Radiation fibrosis Tissue scarring Retained foreign material/implants Osteoporosis Compartment syndrome Obesity	Malnutrition Diabetes mellitus Smoking IV drug abuse Hypoxia Renal/Liver failure Immunosuppression/Deficiency Malignancy Sickle cell disease Drug therapy/Allergies Mental illness

Group C hosts have either severe comorbidities that can prevent adequate treatment, or have symptoms from their infection that are minor and do not merit the risks of curative surgery.

The anatomic staging of osteomyelitis is based on the specific distribution of infected bone in the limb. There are four types, each of which tends to be related to a particular etiology of infection (▶ Fig. 5.5).

**Fig. 5.5 (a–d)** The anatomic types of the Cierny and Mader classification for osteomyelitis (with drawings and magnetic resonance imaging [MRI] and computed tomography [CT] pictures). **(a)** Type 1 Medullary. This tibia has a central sequestrum and surrounding edematous cancellous bone. There is no involvement of the cortex and no sinus formation. **(b)** Type 2 Superficial. There is a cortical sequestrum with surrounding new bone formation (involucrum). The magnetic resonance short-tau inversion recovery (MR STIR) image confirms that there is no medullary infection. **(c)** Type 3 Localized. This is the most common type of osteomyelitis in the long bones. There is medullary and cortical involvement, with sinus formation and subperiosteal stripping of the external cortical surface (*black arrow*). The bone remains in continuity, with a healthy bridge of bone crossing the infected zone, seen at the posteromedial aspect of the femur in this MRI scan (*white arrow*). **(d)** Type 4 Diffuse. An entire segment of the bone is infected. All the features of types 1 to 3 are present. (Reproduced with permission from: McNally MA. Infection after fracture. In: Kates SL, Borens O, eds. Principles of Orthopedic Infection Management. AO Trauma Thieme Verlag; 2016:139–165.)

5.3.1 Type 1 (Medullary)

In Type 1, only medullary cancellous bone is involved. There are no sinuses and the surrounding soft tissues may be inflamed but are not involved in the infection. Structural stability is rarely affected. It is mostly an acute hematogenous infection in childhood. It is uncommon in adults, occurring mainly in those who are immunocompromised, are bacteremic, or have sickle cell disease. Brodie’s abscess is a subacute form of type 1 osteomyelitis.

5.3.2 Type 2 (Superficial)

In this stage, only the outer part of the cortical bone is affected. It is a contiguous infection arising from an overlying area of skin loss usually following injury, venous insufficiency, burns, or pressure ulceration. Common sites are over the mid-tibia, olecranon, ischial tuberosity, and malleoli.

5.3.3 Type 3 (Localized)

This is the most common form of osteomyelitis, usually complicating an open fracture or inadequately treated acute medullary disease. Involvement of the medullary bone and cortex is present, but affects only a part of the circumference of the bone. There is always a healthy bridge of bone crossing the infected zone, which maintains stability.

5.3.4 Type 4 (Diffuse)

This involves the entire circumference of the bone and surrounding soft tissues. All infected fracture nonunions are type 4, and many longstanding hematogenous infections will become diffuse with cortical involvement and extensive subperiosteal abscess formation.

The Cierny and Mader classification has been widely adopted, but it does not include two of the major features of infection that dictate therapy and outcome: the condition of the soft tissues and the microbiological diagnosis. To address this, the BACH classification has been developed (Bone Involvement, Antimicrobial Options, Coverage by Soft Tissue, Host Status) (▶ Fig. 5.6). ¹¹ This has been shown to be easily applied with very high interobserver agreement, and it also correlates with final outcomes in patients after treatment of long bone osteomyelitis. ¹² It divides patients into “Uncomplicated,” “Complex,” and “Limited options for curative treatment.” This allows assessing clinicians to identify the components of treatment and to refer complex patients early to specialist infection centers.

**Fig. 5.6** The BACH classification of osteomyelitis.

5.4 Diagnosis

5.4.1 Clinical Features

The diagnosis of any bone infection is primarily clinical. Local signs of inflammation (pain, swelling, erythema, and warmth) are common, but systemic upset is variable and may be absent, even in acute cases. Around 50% of children with hematogenous osteomyelitis present without fever after a period of up to 3 months of vague limb symptoms. ¹³

Chronic infection may be even more difficult to diagnose. Pain unrelated to activity is the only common symptom, but is rather nonspecific. Acute systemic upset is less prominent but many report fevers, rigors, sweating attacks, and anorexia occurring with flare-ups of the disease.

Examination reveals bony tenderness, subtle swelling, or increased temperature. In recurrent chronic osteomyelitis, there may be signs of old healed sinuses, active discharging sinuses, soft-tissue abscesses, or scars from previous surgery or injury.

Although acute osteomyelitis can produce major systemic illness with potential mortality, chronic disease is less dramatic, but equally life-changing. Chronic osteomyelitis, with recurrent need for medical treatment, poor general health, with or without sinus drainage, and ongoing pain, can result in unemployment and social isolation. Such patients have been shown to have a high risk of depression and other mental illness. ¹⁴

5.4.2 Laboratory Tests

There are no specific blood tests that can confirm or exclude the diagnosis of bone infection. In acute presentation, the serum white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels may be raised due to osteomyelitis or other comorbidities or infection, but they are often normal in chronic infection. In children, the combination of CRP and ESR gave the best sensitivity (98%) for diagnosis of osteoarticular infection. ¹³ ^, ¹⁴

If the patient is pyrexial, blood cultures should always be taken before administration of antibiotics. ¹³ Around one-third of children with acute osteomyelitis will have positive blood cultures. ¹³

Atypical infection with Brucella, Bartonella, or Spirochetes (syphilis and yaws) can be diagnosed with blood serology.

5.4.3 Imaging

Plain radiology remains the best screening test for bone infection (▶ Fig. 5.7a). Initially, the X-ray may be normal but within 5 to 7 days, localized osteopenia, bone destruction, cortical breeches, periosteal reaction, and involucrum become apparent. Sequestra may be seen at around 10 days. During treatment, disuse of the limb produces generalized radiographic osteopenia. Any residual dead bone will remain radiodense, as avascular bone cannot be demineralized, and will become more obvious with time.

**Fig. 5.7 (a–e)** Imaging modalities for osteomyelitis. **(a)** This plain X-ray shows features of chronic osteomyelitis with central sequestration (*black arrow*), bone lysis (*asterisk*), and mature involucrum formation (*white arrows*), causing thickening of the cortex. **(b)** Computed tomography (CT) of a tibia with extensive medullary osteomyelitis, previously treated with reaming. The residual endosteal sequestra (*white arrows*) are seen as radiodense areas under the thickened cortex. **(c)** Short-tau inversion recovery (STIR) and **(d)** T2 magnetic resonance imaging (MRI) images show central osteomyelitis with a sequestrum (*white arrow*), posterior cloaca, and sinus track (*black arrows*) to the subcutaneous tissue and a secondary area of bone lysis in the femur. Sinuses typically take the “route of least resistance” between muscles, along the intermuscular septum. **(e–g)** In this case of infection around an intramedullary nail, the MRI scan **(e)** shows the lateral soft-tissue inflammation well (*black arrows*) but cannot identify the area of bone involvement due to metal artefact. ¹⁸FDG PET-CT **(f)** coronal and **(g)** axial views show the medullary infection around the nail and demonstrate a cloaca passing posteriorly, forming a subperiosteal abscess (*white arrows*).

Contrast sinography is indicated when there is any concern about extension of the infection to an implant or internal viscera. In pelvic osteomyelitis, sinography or retrograde urethrocystography can diagnose fistulas between the bone and bladder or bowel, which is often seen following radiotherapy for bladder or prostate cancer, or in patients with inflammatory bowel disease.

Ultrasound is invaluable for early identification of soft-tissue abscesses and joint effusions. It also allows for guided biopsy of infected areas and limited drainage of painful subperiosteal collections.

Computed tomography (CT) can identify bone destruction and periosteal reaction early, but is not diagnostic for osteomyelitis. Fine-cut CT can identify small sequestra and aid in the design of limited surgical approaches to excise disease (▶ Fig. 5.7b).

Magnetic resonance imaging (MRI) is the investigation of choice in osteomyelitis. It is highly sensitive for diagnosis (>99%), and a normal MRI almost excludes bone infection. ¹⁵ It can show early medullary changes and define the extent of the infection around bone in the soft tissues. In T2-weighted images, water is bright and the MRI may show extensive areas of high signal in the medulla. This may overestimate the extent of the infection, as some of the peripheral high signal may be due to reactive edema. Short-tau inversion recovery (STIR) images are more sensitive in demonstrating fluid in osteomyelitis (▶ Fig. 5.7c, d). T1 images show good anatomical detail and can also identify cortical bone involvement. Usually, cortical bone (normal, infected, or dead) appears black on all MRIs, but subtle changes on the bone surface or in the adjacent soft tissues can suggest type 2 cortical osteomyelitis.

MRI specificity is limited by the presence of metal implants and is affected by recent surgery. ¹⁶ Artifact reduction techniques have been investigated, ¹⁷ but the images are still difficult to interpret, particularly for surgical planning. Postoperative MRI changes may persist for many months and can be difficult to distinguish from recurrent infection. It should not be used to monitor response to treatment.

Bone scintigraphy has been advocated with bone tropic isotopes (⁹⁹m Tc or ⁶⁸Gallium Citrate). Although these tests exhibit high sensitivity for infection, they are nonspecific and lack resolution. ¹¹¹In or ^99mTc-labelled WBC scintigraphy and antigranulocyte antibody scintigraphy have been shown to be accurate for the diagnosis of FRI, but anatomical resolution remains poor. ¹⁸

More recently, new camera systems have allowed nuclear techniques, such as single photon emission computed tomography (SPECT) or fluorodeoxyglucose positron emission tomography (¹⁸FDG-PET), to be combined with localizing scans (CT or MRI) giving excellent diagnostic accuracy and good resolution, even in the presence of metal implants. ¹⁵ ^, ¹⁶ ¹⁸ FDG-PET with CT scanning is quicker and more convenient for patients. It allows very good visualization of dead bone and clearly defines areas of active infection. It is difficult to interpret within 1 month of injury or surgery, whereas WBC scintigraphy may be more accurate. ¹⁸ ¹⁸ FDG-PET with CT is very valuable in surgical planning, particularly when MRI is not available or when metal implants are present (▶ Fig. 5.7e–g). ▶ Fig. 5.8 summarizes the use of imaging in diagnosis and surgical planning.