Osteomyelitis refers to an infection of the bone marrow which may spread to the bone cortex and periosteum via the Haversian canals.^1,2 It results in inflammatory destruction of the bone and if the periosteum becomes involved, necrosis. When dead bone becomes detached from healthy bone, it is known as a sequestrum.

A large sequestrum that remains in situ acts as a focus for ongoing infection. An involucrum refers to viable periosteum that has become separated from the underlying bone and which forms new bone around it. In acute and chronic disease, there is subsequent bone remodelling and often, associated deformity. The most common site of infection is the distal femur and the proximal tibia in children and cancellous bone in adults but ultimately any bone may be affected.³

Osteomyelitis may be acute or chronic (>6 months' duration)⁴ and can be further categorised into two main subgroups:²

Haematogenous osteomyelitis

• This is an infection resulting from haematological bacterial seeding from a remote source.
• It is the type of osteomyelitis more commonly associated with children where it tends to occur in the rapidly growing and highly vascular metaphysis of growing bones.⁵
• Haematogenous osteomyelitis is also seen in patients with distant foci of infection, such as those with infected urinary catheters.

Direct (contiguous) osteomyelitis

• This type of infection occurs where there is direct contact of infected tissue with bone as may occur during a surgical procedure or following trauma.
• Clinical signs tend to be more localised and there are often multiple organisms involved.

Pathogens

There are a number of possible pathogens but Staphylococcus aureus is by far the most common, accounting for 90% of acute osteomyelitis cases.^4,6 In about 5% of cases, more than one organism may be involved.

• Staphylococcus aureus including strains of MRSA
• Haemophilus influenzae
• Streptococcus spp.
• Escherichia coli
• Proteus spp.
• Pseudomonas spp.
• Coagulase-negative Staphylococcus spp.
• Mycobacteria
• Fungi

Epidemiology

• There is a UK incidence of about 10-100/100,000 population per year for acute haematogenous osteomyelitis.^1,2 This is higher in developing countries.
• Prevalence of osteomyelitis after a foot puncture is thought to be as high as 16%, rising to 30-40% in diabetic patients.
• There is a bimodal age distribution with acute, haematogenous osteomyelitis occurring predominantly in males between 3 and 12 years old.⁶
• Contiguous osteomyelitis (often associated with direct trauma) is more frequently seen in adolescents and adults.
• Spinal osteomyelitis is rare before the age of 45.

Risk factors

• Trauma (orthopaedic surgery or open fracture)
• Prosthetic orthopaedic device
• Diabetes
• Peripheral vascular disease
• Chronic joint disease
• Alcoholism
• Intravenous drug abuse
• Chronic steroid use
• Immunosuppression
• Tuberculosis
• HIV and AIDS
• Sickle cell disease
• Presence of catheter-related blood stream infection⁴

Presentation

Haematogenous osteomyelitis

Long bone

• Classic presentation³
  • The acutely febrile and bacteraemic patient presents with markedly painful, immobile limb.
  • There may be swelling and extreme tenderness over the affected area with associated erythema and warmth.
  • The pain is exacerbated by movement and there may be sympathetic effusion of neighbouring joints.⁴
  • In neonates and infants, there may be an associated septic arthritis.¹
• Other presentations⁵
  • Occasionally, the patient may present with mild symptoms, perhaps a history of blunt trauma to the area which may or may not be remembered (e.g. a bump against a hard surface) 24-48 hours previously and mild or no pyrexia.
  • There may be non-specific systemic malaise attributed to a viral illness and suspicions are only raised as the symptoms localise after several days.

Vertebral²

• This usually presents insidiously following an acute septicaemic episode.
  • There may be localised oedema, erythema and tenderness ± associated contiguous vascular insufficiency.
  • Alternatively, these patients can present with chronic back pain which is worse at rest and unremitting in nature.
  • They may specifically complain of night pain. It may be associated with non-specific malaise.¹
• Pott's disease:⁶
  • Refers to vertebral osteomyelitis resulting from the haematogenous spread of tuberculosis.
  • There is damage to the bodies of two neighbouring vertebrae leading to vertebral collapse and subsequent abscess formation (known as a 'cold abscess').
  • Pus can track out from there into adjacent structures leading to systemic symptoms of malaise, fever and night sweats.

Contiguous osteomyelitis

• Patients tend to present in the classic manner with fever, pain and erythema (see above).
• However, they may have an associated history of accidental or surgical trauma (including dental procedures).

Diabetic foot ulcers

• May be present and the pain masked by neuropathy.
• Clinical diagnosis may be complicated by the absence of local signs of infection, such as purulent drainage and local erythema, warmth, and tenderness.
• Often the only systemic sign of diabetic foot osteomyelitis is recalcitrant hyperglycemia; fever and chills are absent in up to two thirds of patients.⁷

Chronic osteomyelitis

Patients may have all or only a few of the following:

• Previous acute infection (either unresponsive to treatment or relapsing following treatment)
• Localised bone pain
• Erythema and swelling over affected area
• Non-healing ulcer
• Draining sinus tracts
• Decreased range of motion of adjacent joints
• Chronic fatigue
• Generalised malaise

Occasionally, the infection becomes localised to form a chronic abscess (Brodie's abscess) within the bone. These patients may be asymptomatic for months or years or may have a history of intermittent, localised pain.⁶

Differential diagnosis

• Cellulitis
• Trauma (soft tissue injury/fracture)
• Other causes of limp
• Gout
• Spinal cord neoplasm
• Acute sickle cell disease crisis

Patients presenting with a history of trauma may pose a diagnostic difficulty as the initial symptoms may be similar to early osteomyelitis. The key is that symptoms should rapidly settle following minor trauma; continued pain and swelling to the initial injury as well as raised inflammatory markers can help confirm clinical suspicion of osteomyelitis. It is therefore important to tell patients being discharged with a history of minor trauma to return if their symptoms do not settle or if they become systemically unwell.⁵

Investigations

Laboratory tests⁴

• Full blood count (white cells are usually up) and inflammatory markers (ESR and CRP are normal in only 2% of osteomyelitis patients⁵).
• Blood cultures are mandatory and positive in ~60% of cases (unless there is localisation of the infection into an abscess or where there is underlying vascular insufficiency).
• Any expressed pus needs to be cultured, as do samples from joint effusion taps and any potential primary sources (e.g. urine).
• Bone cultures (or curettage where there are associated ulcers) provide the gold standard for diagnosis, with a positive test in ~90% of patients.
• Specifically inform the lab if you suspect mycobacterial or fungal infections, as these require different growth media.
• Where chronic osteomyelitis is suspected, diagnosis may be a little more tricky as blood cultures are rarely positive and samples from sinus tracts are unreliable. You may wish to consider Staphylococcus aureus serodiagnosis using the anti-staphylolysin test (65% of cases give raised titres: serial measurements at bi-weekly intervals for 4-6 weeks yield the best results) ± the anti-nuclease test.⁸ If a bone biopsy is performed, it should be done through non-infected tissue.

Imaging

• MRI is the imaging modality of choice for investigation of acute osteomyelitis, allowing good visualisation of even subtle abnormalities.⁹
• Plain X-ray films may be helpful in the diagnosis of chronic osteomyelitis (look for patchy osteopenia and signs of bone destruction) but its use is limited in acute cases where early signs of soft tissue swelling only become apparent after at least 2-3 days. A periostial reaction cannot be seen until about 7 days and bone necrosis after 10 days.¹

Staging⁴

The Cierny-Mader staging system is used. It is determined by the status of the disease process regardless of its aetiology, regionality or chronicity. It takes into account the state of the bone, the patient's overall condition and factors affecting the development of osteomyelitis.

Management⁴

General principles

• Early clinical suspicion, confirmation through imaging and microbiological tests and prompt treatment are the keys to a successful outcome.
• Analgesia (and limb splinting if a long bone is involved) is an important part of symptom control.¹
• Exact treatment varies according to the bones involved, the severity of the infection and the immune status of the patient.
• Surgery may be needed to debride the bone and close any defects.

• Treatment for acute infection is usually for 4-6 weeks and chronic infection for at least 12 weeks.
• High doses are required to achieve suitable concentrations in necrotic avascular bone.
• Intravenous treatment is used initially and also to cover any surgical period, up to two weeks post surgery. The switch to oral therapy may happen once the clinical condition stabilises, the inflammatory markers are going down and there are reliable microbiology results.
• Although treatment is guided by clinical response and the level of inflammatory markers, an early drop in CRP shouldn't tempt early discontinuation of antibiotics - expect to be treating the patient for no less than 4 weeks. Changes on plain X-ray lag at least 2 weeks behind normalisation of CRP.
• Specifically consult the microbiologists if there is a risk of MRSA or if there is a prosthetic device in situ. Microbiologists will also be able to help in the case of polymicrobial infection.
• Rifampicin should not be used alone as antimicrobial resistance rapidly develops.

• It is usually appropriate to delay treatment until culture and sensitivity results are obtained, unless the infection is severe, in which case empirical treatment is started as above.
• Surgical debridement is the mainstay of treatment (it removes the necrotic tissue and provides an infection-free scaffold for future healing).
• If surgery is not possible, indefinite antimicrobial therapy may be required but this is generally accepted to be less effective than surgery.

Osteomyelitis and the diabetic foot ulcer⁷

• These patients are at increased risk of developing osteomyelitis, particularly in the foot, and of subsequent need for lower limb amputation.
• If osteomyelitis is suspected, treat as above.
• However, if the MRI is negative, it is worth treating empirically for two weeks with antibiotics and re-imaging to exclude the possibility that early osteomyelitis may have been missed.

Complications^2,5

• Bone abscess
• Bacteraemia
• Fracture
• Growth arrest
• Septic arthritis
• Loosening of the prosthetic implant
• Overlying soft-tissue cellulitis
• Chronic infection

Prognosis

• This is variable depending on the number of risk factors and the patient's general condition (see Staging above).²
• Outcome is best if treatment is started 3-5 days after onset of the infection.⁴
• Timely diagnosis and intervention in an otherwise well patient should lead to full recovery, although follow-up over several months will be required to monitor for relapse.

Prevention

It is not possible to prevent osteomyelitis but limitation of its effects is through awareness of risk factors, early suspicion and prompt treatment.

Document references

1. Berendt AR and McNally M in Oxford Textbook of Medicine, 4th edition, OUP(2003). Eds; Warrell DA et al.
2. King RW, Johnson D; Osteomyelits. eMedicine, 2009.
3. Lissauer, T. and Clayden, G. Illustrated textbook of Paediatrics, 1997, Mosby.
4. British Society for Antimicrobial Chemotherapy; Osteomyelitis.
5. Ferguson LP, Beattie TF; Osteomyelitis in the well looking child - lesson of the week. BMJ 2002;324:1380-1381.
6. Kumar P; Clarke M; Clinical Medicine, 6th Ed, (2005). WB Saunders: London.
7. Schinabeck MK, Johnson JL; Osteomyelitis in diabetic foot ulcers. Prompt diagnosis can avert amputation. Postgrad Med. 2005 Jul;118(1):11-5. [abstract]
8. Health Protection Agency; Staphylococcus aureus serodiagnosis
9. McAndrew PT, Clark C; MRI is best technique for imaging acute osteomyelitis. BMJ 1998; 316:147.

Acknowledgements