Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis

INTRODUCTION — Osteomyelitis is an infection involving bone. Osteomyelitis may be classified based on the mechanism of infection (hematogenous versus nonhematogenous) and the duration of illness (acute versus chronic) [1].

Issues related to the classification, epidemiology, microbiology, clinical manifestations, and diagnosis of osteomyelitis in adults are presented here. Issues related to treatment of osteomyelitis are discussed separately. (See "Nonvertebral osteomyelitis in adults: Treatment".)

Issues related to vertebral osteomyelitis, pelvic and sacral osteomyelitis, and osteomyelitis in the setting of trauma are discussed in detail separately. (See "Vertebral osteomyelitis and discitis in adults" and "Pelvic osteomyelitis and other infections of the bony pelvis in adults" and "Osteomyelitis associated with open fractures in adults".)

Issues related to prosthetic joint infections are discussed separately. (See "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Issues related to osteomyelitis in children are discussed separately. (See "Hematogenous osteomyelitis in children: Evaluation and diagnosis" and "Hematogenous osteomyelitis in children: Management".)

CLASSIFICATION — Osteomyelitis may be classified based on the duration of illness (acute versus chronic) and the mechanism of infection (hematogenous versus nonhematogenous). This approach to classification was described by Lew and Waldvogel [2-4].

Acute osteomyelitis typically presents with a symptom duration of a few days or weeks. Sequestra (pieces of necrotic bone that separate from viable bone) are absent.

Chronic osteomyelitis is characterized by long-standing infection over months or years. Sequestra are usually present; they form as a result of bone ischemia and necrosis in the context of blood vessel compression due to elevated medullary pressure associated with bone marrow inflammation. Sequestra can be seen radiographically. The presence of a sinus tract is pathognomonic of chronic osteomyelitis. (See "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis".)

Nonhematogenous osteomyelitis can occur as a result of contiguous spread of infection to bone from adjacent soft tissues and joints or via direct inoculation of infection into the bone (as a result of trauma or surgery).

Hematogenous osteomyelitis is caused by microorganisms that seed the bone in the setting of bacteremia.

NONHEMATOGENOUS OSTEOMYELITIS — Nonhematogenous osteomyelitis can occur as a result of contiguous spread of infection to bone from adjacent soft tissues and joints or via direct inoculation of infection into the bone (as a result of trauma, bite wounds, or surgery).

Epidemiology — Among younger adults, nonhematogenous osteomyelitis occurs most commonly in the setting of trauma and related surgery. Among older adults, nonhematogenous osteomyelitis occurs most commonly as a result of contiguous spread of infection to bone from adjacent soft tissues and joints (such as in the setting of diabetic foot wounds or decubitus ulcers) [2].

Risk factors for nonhematogenous osteomyelitis include poorly healing soft tissue wounds (including decubitus ulcers), presence of orthopedic hardware, diabetes, peripheral vascular disease, and peripheral neuropathy.

Microbiology — Nonhematogenous osteomyelitis may be polymicrobial or monomicrobial. Staphylococcus aureus (including methicillin-resistant S. aureus), coagulase-negative staphylococci, and aerobic gram-negative bacilli are the most common organisms. In one study, staphylococci were isolated in 53 percent of bone biopsy specimens, enterococci in 8 percent, streptococci in 12 percent, and anaerobes in 5 percent [5].

Other pathogens including corynebacteria, fungi, and mycobacteria have also been implicated [4-10].

Clinical manifestations

Signs and symptoms — Acute osteomyelitis typically presents with gradual onset of symptoms over several days. Patients usually present with dull pain at the involved site, with or without movement. Local findings (tenderness, warmth, erythema, and swelling) and systemic symptoms (fever, rigors) may also be present. Patients with osteomyelitis involving the hip, vertebrae, or pelvis tend to manifest few signs or symptoms other than pain.

Chronic osteomyelitis may manifest as pain, erythema, or swelling, sometimes in association with a draining sinus tract; fever is usually absent. Chronic osteomyelitis may also present with intermittent flares of pain and swelling. The presence of a sinus tract is pathognomonic of chronic osteomyelitis.

The diagnosis of chronic osteomyelitis can be particularly challenging when prosthetic material, extensive skin or soft tissue ulceration, or ischemic changes due to vascular insufficiency are also present [11]. Deep or extensive ulcers that fail to heal after several weeks of appropriate ulcer care should raise suspicion for chronic osteomyelitis, particularly when such lesions overlie bony prominences [11,12]. Chronic osteomyelitis may also present as a nonhealing fractures.

Patients with diabetes and chronic osteomyelitis may present with atypical findings. Diabetics who develop cutaneous ulcers often develop osteomyelitis before exposed bone is present on exam [11]. If a diabetic foot ulcer is larger than 2 cm² or if exposed bone is present, osteomyelitis is highly likely [11,13]. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities".)

Osteomyelitis of the foot may develop following nail puncture through a shoe; Pseudomonas aeruginosa is a typical pathogen in such cases. (See "Infectious complications of puncture wounds" and "Pseudomonas aeruginosa skin and soft tissue infections", section on 'Infection following nail puncture'.)

Probing to bone — Probing to bone with a sterile blunt metal tool should be included in the initial assessment of diabetic patients with infected pedal ulcers. A positive result consists of detection of a hard, gritty surface [12-14]. The reliability of the probe-to-bone test may vary by the ulcer location and the expertise of the clinician performing the test [15,16].

The performance characteristics of the test have been evaluated in the setting of diabetic foot ulcers. In practice, the test is also used for evaluating nondiabetic ulcers due to peripheral neuropathy, vasculopathy, or pressure sores, although the performance characteristics have not been evaluated in these settings.

In a systematic review evaluating the performance of the probe-to-bone test (using bone histopathology or culture as the reference standard), the pooled sensitivity and specificity for the test were 87 and 83 percent, respectively [17]. An important limitation was the potential for selection and verification bias; the studies included in the analysis did not specify whether the results of the probe-to-bone test influenced pursuit of bone biopsy or culture nor whether interpreters of the reference standard were blinded to results of the probe-to-bone test.

The probe-to-bone test should be used as a screening tool in conjunction with the patient's pretest probability for osteomyelitis to determine whether additional tests (such as radiographic imaging or bone biopsy) are needed for diagnosis of diabetic foot osteomyelitis [18].

Laboratory tests — Laboratory findings are nonspecific. In the setting of acute osteomyelitis, leukocytosis and elevated serum inflammatory markers (erythrocyte sedimentation rate [ESR] and/or C-reactive protein [CRP]) may be observed [19,20]. In the setting of chronic osteomyelitis, leukocytosis is uncommon; the ESR and/or CRP may be elevated or normal [21,22].

HEMATOGENOUS OSTEOMYELITIS — Hematogenous osteomyelitis is caused by microorganisms that seed the bone in the setting of bacteremia.

Epidemiology — Hematogenous osteomyelitis occurs most commonly in children [23]. (See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology".)

Vertebral osteomyelitis is the most common form of hematogenous osteomyelitis in adults. Issues related to vertebral osteomyelitis are discussed separately. (See "Vertebral osteomyelitis and discitis in adults".)

Among adults, hematogenous osteomyelitis accounts more frequently in males. Most cases occur in patients >50 years [24], except for injection drug users, most of whom are <40 years of age [25].

Risk factors for hematogenous osteomyelitis include endocarditis, presence of indwelling intravascular devices (eg, vascular catheters, cardiovascular devices) or orthopedic hardware, injection drug use, hemodialysis, and sickle cell disease [26].

Microbiology — Hematogenous osteomyelitis occurs following bacteremia. Patients may present following clearance of bacteremia, so blood cultures are not always positive.

Hematogenous osteomyelitis is usually monomicrobial; S. aureus is by far the most commonly isolated organism. In some cases, hematogenous osteomyelitis due to S. aureus presents with multifocal involvement [2,27-29]. Aerobic gram-negative rods are identified in up to 30 percent of cases.

Among injection drug users, hematogenous osteomyelitis due to P. aeruginosa and Serratia marcescens has been described [30]. Among immunosuppressed patients, hematogenous osteomyelitis due to Aspergillus spp has been described [31].

Hematogenous osteomyelitis due to beta-hemolytic streptococci is relatively rare (<1 percent of cases) [32]. Other less common pathogens include Mycobacterium tuberculosis [33], Candida spp [34-36], Bartonella henselae [37], Coccidioides immitis [38,39], and Cutibacterium (formerly Propionibacterium) acnes [40].

Clinical manifestations

Signs and symptoms — In general, signs and symptoms of hematogenous osteomyelitis may be indistinguishable from those of nonhematogenous osteomyelitis, discussed above. (See 'Signs and symptoms' above.)

Signs and symptoms referable to specific forms of hematogenous osteomyelitis are discussed in the following sections.

Forms of disease — Clinical manifestations of hematogenous osteomyelitis mirror those of nonhematogenous osteomyelitis. (See 'Clinical manifestations' above.)

Clinical presentations that are unique to hematogenous osteomyelitis are discussed in the following sections. In some cases, adults with hematogenous osteomyelitis may have no local symptoms referable to bones; soft tissue findings may be more prominent.

●Vertebral osteomyelitis – Vertebral osteomyelitis is the most common form of hematogenous osteomyelitis in adults. Issues related to vertebral osteomyelitis are discussed separately. (See "Vertebral osteomyelitis and discitis in adults".)

●Sternoclavicular and pelvic osteomyelitis – After vertebral osteomyelitis, next most common sites of hematogenous osteomyelitis in adults are the flat bones of the axial skeleton (such as the sternoclavicular and pelvic bones). These sites are involved most frequently among injection drug users; multifocal involvement may be observed in these patients [41-43].

Specific signs and symptoms of sternoclavicular osteomyelitis include anterior chest wall swelling, pain, and tenderness. Sternoclavicular osteomyelitis may present as a mass that is mistaken for a soft tissue abscess or atypical cellulitis. It can also present as infection of the manubriosternal symphysis (a fibrocartilage union of the manubrium and the body of the sternum). In addition, sternoclavicular osteomyelitis can develop as a complication of mediastinitis. Local symptoms include pain, swelling, erythema, and tenderness over the sternoclavicular joint, and infection can extend into the surrounding soft tissue including the pectoralis major. (See "Postoperative mediastinitis after cardiac surgery".)

Issues related to pelvic osteomyelitis are described separately. (See "Pelvic osteomyelitis and other infections of the bony pelvis in adults".)

●Long-bone osteomyelitis – The least common sites of hematogenous osteomyelitis in adults are the long bones of the appendicular skeleton (in contrast, this is the most common site of hematogenous osteomyelitis in children) [44]. The clinical presentation is variable; some present subacutely with low-grade fever and vague pain at the site of infection, while others present acutely with high fever, sharp pain, and swelling over the involved site. Long-bone osteomyelitis may be classified based on the degree of bone involvement as well as host factors (table 1) [45]. (See "Hematogenous osteomyelitis in children: Clinical features and complications".)

Long-bone osteomyelitis can also present as septic arthritis of the knee, hip, or shoulder. This occurs if infection within the metaphysis (the most common site of infection in long-bone osteomyelitis) breaks through the bone cortex, leading to discharge of pus into the joint. The clinical manifestations, diagnosis, and management of septic arthritis are described separately. (See "Septic arthritis in adults".)

•Brodie abscess – A Brodie abscess consists of a region of suppuration and necrosis encapsulated by granulation tissue within a rim of sclerotic bone. Brodie abscess occurs in the setting of subacute or chronic osteomyelitis in the metaphysis of long bones, typically in patients <25 years of age [46]. It is usually of hematogenous origin but can also occur in the setting of trauma.

The most common pathogen is S. aureus; other gram-positive and gram-negative organisms (including P. aeruginosa, Klebsiella spp, and other gram-negative rods) may be seen. Cultures may be sterile in up to half of cases.

Patients with Brodie abscess typically present with insidious onset of mild to moderate pain lasting for several weeks to months, with or without fever. If the subacute process progresses to chronic localized bone abscess, patients present with longstanding dull pain in the absence of fever [47,48]. The most common site is the distal tibia; other sites include the femur, fibula, radius, and ulna [49].

Radiography typically demonstrates a single lesion near the metaphysis (image 1).

•Osteomyelitis in sickle cell disease – Osteomyelitis is a common complication of sickle cell disease; it occurs in more than 10 percent of patients [1]. This issue is discussed further separately. (See "Acute and chronic bone complications of sickle cell disease", section on 'Osteomyelitis and septic arthritis'.)

●Emphysematous osteomyelitis - Emphysematous osteomyelitis is a rare form of osteomyelitis characterized by intraosseous gas in the extra-axial skeleton (eg, pelvis, sacrum, femur) or vertebrae [50-53]. It can occur via hematogenous spread or via contiguous spread from an intra-abdominal source, is usually associated with underlying comorbidities (eg, diabetes or malignancy), and may be monomicrobial or polymicrobial. The most commonly associated organisms include Enterobacteriaceae and Fusobacterium necrophorum.

COMPLICATIONS — Complications of osteomyelitis include both infectious and noninfectious complications.

Infectious complications — Infectious complications generally occur as a consequence of spread from the bone to adjacent tissues or elsewhere in the body, and include the following:

●Sinus tract formation

●Contiguous soft tissue infection

●Abscess

●Septic arthritis

●Systemic infection

Noninfectious complications — Osteomyelitis can lead to permanent bone damage that may result in bony deformity or increased risk for bone fracture [54].

Cases of carcinoma, including squamous cell carcinoma and sarcoma, at the site of chronic osteomyelitis have been reported, mostly in individuals with osteomyelitis of an extremity [55-65]. Histopathologic examination of a tissue biopsy can differentiate infection from carcinoma.

DIAGNOSIS

Overview — A clinical presentation of osteomyelitis should be suspected in the following circumstances:

●Nonhematogenous osteomyelitis should be suspected in the setting of new or worsening musculoskeletal pain, particularly in patients with poorly healing soft tissue or surgical wounds adjacent to bony structures, in patients with signs of cellulitis overlying previously implanted orthopedic hardware, and in patients with traumatic injury (including bite and puncture wounds). It should also be suspected in diabetic patients with ulcers that probe to bone.

●Hematogenous osteomyelitis should be suspected in the setting of new or worsening musculoskeletal pain, particularly in the setting of fever and/or recent bacteremia.

In general, the diagnosis of osteomyelitis is established via culture obtained from biopsy of the involved bone [12].

A diagnosis of osteomyelitis may be inferred in the following circumstances:

●Clinical and radiographic findings typical of osteomyelitis and positive blood cultures with a likely pathogen (such as S. aureus); in such cases, bone biopsy is not required but may be useful, particularly if subsequent therapeutic debridement is needed.

●Bone histopathology consistent with osteomyelitis in the absence of positive culture data (particularly in the setting of recent antibiotic administration).

●Suggestive clinical and typical radiographic findings and persistently elevated inflammatory markers in circumstances with no positive culture data and a biopsy is not feasible.

Issues related to diagnosis of vertebral osteomyelitis are discussed separately. (See "Vertebral osteomyelitis and discitis in adults".)

Clinical approach — Initial evaluation of patients with suspected osteomyelitis includes history and physical examination; predisposing factors or events should be elicited (such as underlying diabetes, vasculopathy, invasive procedures, or injection drug use). (See 'Epidemiology' above and 'Epidemiology' above.)

If osteomyelitis is suspected based on clinical history and physical findings, laboratory evaluation (including erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], white blood cell count), blood cultures, and radiographic imaging should be obtained. ESR and CRP are sensitive but not specific for osteomyelitis; if elevated initially, they can be useful for treatment monitoring. (See "Nonvertebral osteomyelitis in adults: Treatment", section on 'Monitoring during treatment'.)

In patients with ≥2 weeks of symptoms, conventional radiography is a reasonable initial imaging modality for evaluation of suspected osteomyelitis, which is characterized by osteolysis, periosteal reaction, and bone destruction. In patients with <2 weeks of symptoms, an advanced imaging modality should be pursued. Advanced imaging is also warranted for patients with diabetic foot infections, localized symptoms, and/or abnormal laboratory results whose plain radiographs are normal or suggestive of osteomyelitis without characteristic features [66].

The optimal radiographic modality may depend upon specific clinical circumstances and should be tailored accordingly for individual patients, in discussion with radiologist expertise if necessary. The following concepts may help guide selection of radiographic modality (see "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis"):

●If the patient is diabetic and has symptoms referable to the foot, magnetic resonance imaging (MRI) is the test of choice.

●If metal hardware precludes MRI or computed tomography (CT), a nuclear study is the test of choice. The limitations of nuclear studies are discussed separately and should be considered in interpretation of results.

Findings of osteomyelitis on radiographic imaging should prompt bone biopsy for culture and histology to confirm the diagnosis and to guide antimicrobial therapy, unless blood cultures are positive for a likely pathogen (such as S. aureus, a gram-negative enteric rod, or P. aeruginosa). Osteomyelitis is unlikely in the absence of radiographic evidence on MRI, CT, or nuclear imaging.

If blood cultures and needle aspirate cultures are negative and the clinical suspicion for osteomyelitis remains high on the basis of clinical and radiographic findings, repeat bone biopsy (either percutaneous or open) should be performed. If this specimen is also nondiagnostic, an empiric antimicrobial regimen should be initiated against common gram-positive and gram-negative bacterial pathogens. (See "Nonvertebral osteomyelitis in adults: Treatment".)

If there is evidence of soft tissue infection over a bony surface without radiographic evidence of osteomyelitis, an empiric course of therapy for soft tissue infection may be appropriate [12].

Clinical specimens

Blood cultures — The utility of blood cultures is highest in the setting of hematogenous infection associated with fever or concurrent infective endocarditis [2,67,68]. Blood cultures are rarely positive in diabetic foot osteomyelitis.

Positive blood cultures may obviate the need for a biopsy if the blood isolate is a pathogen likely to cause osteomyelitis. (See 'Microbiology' above.)

Bone biopsy — The identification of the causative pathogen(s) is best accomplished by bone biopsy (open or percutaneous). At least two specimens should be obtained; one should be sent for Gram stain and culture (including aerobic, anaerobic, mycobacterial, and fungal cultures), and the other should be sent for histopathology [69]. The microbiologic yield of bone biopsy (open or percutaneous) is 37 to 87 percent [5,70-73].

Histology is useful if the diagnosis of osteomyelitis is uncertain and, in the setting of amputation, to assess whether surgical margins are free from infection [5,27,70,71,74]. Stains for bacteria, mycobacteria, and fungi should be performed on histopathology specimens. Histopathologic features of osteomyelitis include necrotic bone with extensive resorption adjacent to an inflammatory exudate [75]. (See "Pathogenesis of osteomyelitis".)

Indications — In general, the diagnosis of osteomyelitis is established via culture obtained from biopsy of the involved bone.

Bone biopsy for culture is especially important for patients with diabetic foot infection in the following circumstances:

●Empiric antibiotic therapy has failed.

●There is a concern for antibiotic-resistant organisms requiring targeted antibiotic therapy.

●Presence of a midfoot or hindfoot lesion; these are more difficult to treat, and treatment failure can result in major amputation.

Bone biopsy may not be needed for patients with positive blood cultures and radiographic evidence of osteomyelitis, or in cases of relapse if recent prior bone culture data is available. It may be impractical to obtain a bone biopsy if wound healing is a concern due to advanced vascular disease or other comorbidities; in such cases, empiric treatment should be pursued. (See "Nonvertebral osteomyelitis in adults: Treatment".)

Timing — Ideally, biopsy should be performed before initiation of antibiotic therapy to increase the microbiologic yield. For patients who are already on antibiotics, the optimal antibiotic-free period prior to biopsy is uncertain:

●For patients undergoing percutaneous biopsy, some studies have used a two-week antibiotic-free period to minimize the likelihood of false-negative culture results [72]. However, the potential benefit of more accurate microbiologic data must be weighed against the risk of progressive infection in the absence of treatment (eg, in patients who are febrile, bacteremic, septic, critically ill, neutropenic, neurologically compromised, or experiencing rapid progression of accompanying soft tissue infection).

●For patients undergoing open bone biopsy, cessation of antibiotics 48 to 72 hours is preferred; however, this may not be necessary for cases in which infections occur in association with infarction or necrosis, given limited penetration of antibiotics in such cases.

Technique — For patients who require surgical debridement for definitive management (such as in the setting of a decubitus ulcer or a wound with compromised vasculature), bone samples should be obtained at the time of surgical debridement (ie, open biopsy) for histology and culture [76]. For patients not undergoing debridement, an open biopsy or percutaneous core bone biopsy should be pursued.

Ideally, percutaneous biopsies should be done with radiographic guidance, to minimize the likelihood of false-negative results due to sampling error. Needle placement through infected or ulcerated soft tissue should be avoided to minimize the likelihood of contamination. Two or three specimens should be obtained; at least one should be sent one for culture and one should be sent for histology.

Other specimens — Cultures of swabs, sinus tract, tissue aspirates, or superficial wound biopsy should not be used to establish an osteomyelitis pathogen. In the setting of diabetic foot osteomyelitis, decubitus ulcers, and postoperative and post-traumatic settings, the correlation between bone biopsy and non-bone culture specimens is poor [5,70,72,77].

Sinus tract cultures may be of some use for prediction of osteomyelitis if S. aureus or Salmonella spp are identified; however, in general, such cultures are not worthwhile because the results do not correlate reliably with the pathogen in the underlying bone [5,77-80]. In one report including 40 patients with chronic osteomyelitis, only 44 percent of sinus tract cultures contained the pathogen isolated from a deep surgical specimen [80]. Isolation of S. aureus from the sinus tract culture had some predictive value, although the absence of S. aureus in the sinus tract did not preclude its presence on bone biopsy. Recovery of other organisms in culture is not predictive for those that will be identified on bone biopsy [80].

Swab culture and tissue aspiration are of minimal value. In one study comparing bone culture with swab culture among 76 patients with diabetic foot osteomyelitis who received no antibiotics for at least four weeks prior to culture, the concordance across isolates was low (23 percent overall; 43 percent for S. aureus, 29 percent for gram-negative bacilli, and 26 percent for streptococci) [5]. Similarly, in a study comparing percutaneous bone biopsy with radiographically guided needle aspiration of tissue adjacent to the periosteum, bone biopsy culture correlated with needle aspirate culture only in 32 percent of cases; among patients with a positive bone culture, needle aspirate culture was negative in 38 percent of cases [72].

Sonication of explanted hardware may be useful to detect microorganisms that are highly adherent to fixation hardware, although this procedure is not routinely available in most microbiology laboratories [81-83].

Radiography — The general role of radiographic studies in the diagnosis of osteomyelitis is discussed above. (See 'Clinical approach' above.)

A more detailed discussion of radiographic modalities in the setting of suspected osteomyelitis is discussed separately. (See "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of osteomyelitis includes:

●Soft tissue infection – Soft tissue infection may occur alone or in conjunction with osteomyelitis. In general, it is prudent to pursue imaging for assessment of bone involvement in the setting of chronic soft tissue infection that fails to improve with appropriate antibiotic therapy; this occurs more often in the setting of diabetes. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities".)

●Charcot arthropathy – Acute Charcot neuroarthropathy may present with localized erythema and warmth; it can be difficult to determine if such patients have Charcot arthropathy or osteomyelitis (or both). Furthermore, patients with Charcot arthropathy commonly develop skin ulcerations that can in turn lead to secondary osteomyelitis. Magnetic resonance imaging (MRI; contrast-enhanced) may be diagnostically useful if it shows a sinus tract, replacement of soft tissue fat, a fluid collection, or extensive marrow abnormalities. Bone biopsy may be needed for definitive diagnosis. (See "Diabetic neuroarthropathy".)

●Osteonecrosis – Osteonecrosis (avascular necrosis of bone) is usually relatively easy to distinguish from osteomyelitis since a precipitating cause is usually present (such as steroids, radiation, or bisphosphonate use). Associated osteomyelitis may occur in patients with mandibular osteonecrosis. (See "Risks of therapy with bone antiresorptive agents in patients with advanced malignancy", section on 'Osteonecrosis of the jaw' and "Treatment of nontraumatic hip osteonecrosis (avascular necrosis of the femoral head) in adults".)

●Gout – Both osteomyelitis and gout can present with joint inflammation; the presentation of gout is usually more acute than the presentation of osteomyelitis. Gout is distinguished by presence of uric acid crystals in joint fluid. (See "Clinical manifestations and diagnosis of gout".)

●Fracture – Osteomyelitis may mimic the appearance of fracture on radiographic imaging; fracture is typically associated with antecedent trauma. In some cases, bone biopsy may be required to distinguish these two entities, particularly in the absence of healing following suspected fracture. (See "General principles of fracture management: Early and late complications".)

●Bursitis – Both osteomyelitis and bursitis can present with inflammation of the bursa; osteomyelitis involves infection of the underlying bone whereas bursitis involves infection that is confined to the bursa. The two are distinguished by clinical history, physical examination, radiography, and bursa aspiration. (See "Septic bursitis".)

●Bone tumor – Both osteomyelitis and bone tumor may present with bone pain [84,85]; bone tumor is generally distinguished by radiographic imaging and bone biopsy. (See "Bone tumors: Diagnosis and biopsy techniques".)

●Sickle cell vaso-occlusive pain crisis – In patients with sickle cell disease, the clinical presentation of osteomyelitis may be difficult to distinguish from a vaso-occlusive pain crisis. Osteomyelitis is more likely to be associated with a prolonged duration of fever and pain localized to a single site. (See "Acute and chronic bone complications of sickle cell disease", section on 'Osteomyelitis and septic arthritis'.)

●Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) – SAPHO syndrome consists of a wide spectrum of neutrophilic dermatoses associated with aseptic osteoarticular lesions. It can mimic osteomyelitis in patients who lack the characteristic findings of pustulosis and synovitis. The diagnosis is established via clinical manifestations; bone culture is sterile in the setting of osteitis. (See "SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome" and "Major causes of musculoskeletal chest pain in adults", section on 'Sternocostoclavicular hyperostosis (SAPHO syndrome)'.)

●Complex regional pain syndrome (CRPS) – CRPS is characterized by pain, swelling, limited range of motion, skin changes, and patchy bone demineralization, usually of the distal limbs. It frequently begins following a fracture, soft tissue injury, or surgery. Patients with osteomyelitis lack symptoms of vasomotor instability observed with CRPS. Radiographic evaluation with MRI can differentiate between osteomyelitis and CRPS. (See "Complex regional pain syndrome in adults: Pathogenesis, clinical manifestations, and diagnosis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Osteomyelitis and prosthetic joint infection in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Osteomyelitis in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition and classification – Osteomyelitis is an infection involving bone. Osteomyelitis may be classified based on the source of infection (hematogenous versus nonhematogenous) and the duration of illness (acute versus chronic). (See 'Classification' above.)

●Nonhematogenous osteomyelitis (see 'Nonhematogenous osteomyelitis' above)

•Mechanism of infection – Nonhematogenous infection occurs as a result of contiguous spread of infection to bone from adjacent soft tissues and joints or via direct inoculation of infection into the bone (as a result of trauma, bite wounds, or surgery). (See 'Nonhematogenous osteomyelitis' above.)

•Clinical suspicion – Nonhematogenous infection should be suspected in patients with new or worsening musculoskeletal pain near soft tissue or surgical wounds, in patients with signs of cellulitis overlying previously implanted orthopedic hardware, in patients with traumatic injury (including bite and puncture wounds), and in diabetic patients with ulcers that probe to bone. (See 'Overview' above.)

●Hematogenous osteomyelitis (see 'Hematogenous osteomyelitis' above)

•Mechanism of infection – Hematogenous infection is caused by microorganisms that seed the bone in the setting of bacteremia. (See 'Hematogenous osteomyelitis' above.)

•Clinical suspicion – Hematogenous infection should be suspected in the setting of new or worsening musculoskeletal pain, particularly in the setting of fever and/or recent bacteremia. Vertebral osteomyelitis is the most common form of hematogenous osteomyelitis in adults. (See 'Overview' above and "Vertebral osteomyelitis and discitis in adults".)

●Diagnosis – In general, the diagnosis of osteomyelitis is established via culture obtained from biopsy of the involved bone. A diagnosis of osteomyelitis may be inferred in the following circumstances (see 'Overview' above):

•Clinical and radiographic findings typical of osteomyelitis and positive blood cultures with a likely pathogen (such as Staphylococcus aureus); in such cases, bone biopsy is not required but may be useful, particularly if subsequent therapeutic debridement is needed.

•Bone histopathology consistent with osteomyelitis in the absence of positive culture data (particularly in the setting of recent antibiotic administration).

•Suggestive clinical and typical radiographic findings and persistently elevated inflammatory markers in circumstances with no positive culture data or available biopsy examination.

●Diagnostic evaluation – Patients with suspected osteomyelitis should undergo laboratory evaluation (including erythrocyte sedimentation rate, C-reactive protein, white blood cell count), blood cultures, and radiographic imaging.

•Choice of radiographic test

-In patients with ≥2 weeks of symptoms, conventional radiography is a reasonable initial imaging modality.

-In patients with <2 weeks of symptoms, an advanced imaging modality (magnetic resonance imaging, computed tomography, or nuclear imaging) should be pursued. Advanced imaging is also warranted for patients with diabetes, localized symptoms, and/or abnormal laboratory results whose plain radiographs are normal or suggestive of osteomyelitis without characteristic features. Osteomyelitis is unlikely in the absence of radiographic evidence on advanced imaging. (See 'Clinical approach' above.)

•Role of bone biopsy – Findings of osteomyelitis on radiographic imaging should prompt bone biopsy for culture and histology to confirm the diagnosis and to guide antimicrobial therapy, unless blood cultures are positive for a likely pathogen (such as S. aureus, a gram-negative enteric rod, or Pseudomonas aeruginosa). (See 'Clinical approach' above.)