Osteomyelitis is a complex medical condition initiated by the colonization of host bone tissue by microorganisms. These organisms most commonly gain access through the bloodstream (acute hematogenous osteomyelitis) or contamination from open fractures or surgical interventions, and less commonly through skin defects/ulcers (insensate skin) or direct extension of organisms through infected skin (madura foot/mycetoma).

Among bacterial pathogens, Staphylococcus aureus stands as the predominant culprit across all age groups. However, in individuals with sickling hemoglobinopathies in the United States, Salmonellae are the most prevalent bacterial pathogens. Shoulder surgeries elevate the risk of infection notably due to Cutibacterium acnes, a slow-growing gram-positive rod. Meanwhile, Pseudomonas is frequently implicated in infections stemming from foot puncture wounds. Moreover, the presence of multidrug-resistant bacteria in osteomyelitis significantly increases the risk of complications and prolongs treatment durations, underscoring the importance of vigilant management strategies. Other organisms more prevalent in developing nations may include mycobacteria (tuberculosis), fungi (blastomycosis, other) and parasites (hydatid disease, other).

Bacteria have evolved a number of strategies to evade hosts’ defenses and antibiotics, including forming abscesses, slowing their metabolic rate, becoming intracellular or hiding within bone canaliculi or on necrotic bone, and forming glycocalyx in implant-associated infections. Some more aggressive organisms can “hijack” the host’s inflammatory response, mediated by cytokines such as interleukin-6, potentially leading to complications such as deep vein thrombosis, septic emboli, and even multi-organ system failure.

Acute hematogenous osteomyelitis (AHO) is most common in the pediatric age group, and during an episode of bacteremia, the organisms typically lodge in the metaphysis or metaphyseal equivalents (e.g., pelvis, scapula) due to the unique vascular anatomy in that region. Although most sources point to sluggish flow around loops within the arteriovenous circulation close to the physis, there are also data to suggest that some end vessels simply terminate in this region.

Osteomyelitis represents a spectrum of disease, and the terms acute, subacute, and chronic all represent relative points along a continuum. The clinical course is variable and evolves based on the type of organism and its virulence, the host immune status/inflammatory response, and the impact of medical and surgical interventions. Under ideal circumstances, an organism is identified on culture and the most effective antibiotic delivered; however, in some circumstances empiric treatment is required.

Surgical care plays an important role in establishing the diagnosis, achieving local disease control by drainage of abscesses and removal of infected/devitalized tissues, providing soft-tissue coverage and/or reconstructing skeletal defects, and, in rare cases, mitigating disease reactivation in patients for whom a cure cannot be achieved. Although the condition is commonly cured with prompt treatment when the presentation is acute or subacute, the chances of cure are lower once a chronic disease state is established. In such circumstances, a steady state or standoff is achieved between the organisms and the host, and intermittent acute exacerbations may be observed. Only an aggressive surgical approach with wide resection of all diseased tissues offers a reasonable chance of cure. A multidisciplinary approach involving radiologists, orthopaedic surgeons, infectious disease specialists, and often plastic surgeons is critical in order to achieve a cure or at least long-term disease-free survival.

Diagnosing osteomyelitis can be a challenge. Inflammatory markers are reliably elevated in cases presenting acutely in AHO but may be normal in those with subacute or chronic presentation. Plain radiographs may be normal early on but show a periosteal reaction or bony destruction 10 to 14 days after onset in AHO, or there may be show changes such as implant loosening in implant-associated infections. In addition to obtaining cultures, a biopsy is commonly performed and may be essential in establishing the diagnosis when cultures are negative. Other imaging modalities are used in selected circumstances (most commonly MRI) to diagnose AHO before plain radiographic changes have been observed. Radionuclide imaging is often utilized in adults with implant-associated infections, and CT may be helpful to identify the extent and detail of bony involvement and assist with surgical planning, especially in chronic cases. The diagnosis and treatment of implant-associated osteomyelitis continue to evolve, and multiple bone biopsies are suggested to avoid sinus tracts, which may lead to false-positive isolation of nonpathogenic microbes.

The treatment of acute or subacute infections typically involves antibiotics, often following surgery. AHO patients are typically transitioned from IV to oral therapy within a few days if the clinical response is adequate and the overall duration of therapy has been shortened from approximately 6 weeks to 4 weeks. In the chronic disease state, microorganisms are harbored within avascular bone and soft tissues, rendering them inaccessible to host defenses or antibiotics. In these circumstances, a wide resection with reconstruction of bone and soft-tissue defects offers the best outcomes, assuming the host status is judged to be adequate. Patient selection is crucial in the adult population, and the Cierny-Mader classification helps identify candidates for reconstructive surgery. “A hosts” are all candidates, “B hosts” are selected on a case-by-case basis, and “C hosts” are better served by antibiotic suppression or amputation in selected circumstances.

Additional considerations include nutritional supplementation, discontinuation of nicotine products, and management of co-existing medical conditions. Antibiotics serve as an adjunct to surgical care, and the route and duration of administration remain controversial. Hyperbaric oxygen may also play a role in selected cases. Once a wide resection is achieved after one or more debridements, defects in the soft tissues and/or skeleton are common and typically require staged management. The assistance of a plastic surgeon is often required when a rotational flap, free flap, or osteo-cutaneous flap is needed for coverage. For smaller bone defects, shortened or delayed bone grafting are feasible options. In cases of segmental and larger bone defects, various techniques such as vascularized grafts, bone transport (unifocal or bifocal), the induced membrane technique, or creation of a single bone if a distal upper or lower extremity is involved. Creation of a single-bone forearm is a less invasive salvage strategy but eliminates forearm rotation. In the lower leg, fibular transference procedures have been used for more than 100 years to bypass skeletal defects in the tibia. It may also be necessary to address co-existing problems such as angular deformities and/or limb-length inequality.

In conclusion, osteomyelitis represents a continuum of disease, and management requires prompt diagnosis and a multidisciplinary approach. Organisms have developed a variety of strategies to evade host defenses and acquired resistance to a variety of antibiotics. Treatment is individualized and varies from antibiotics alone to extensive surgical debridement and reconstruction. In most cases, an adequate outcome may be achieved with prompt diagnosis and treatment.

Michael DeRogatis, MD, MS, is an orthopaedic surgery resident at St. Luke’s University Health Network in Bethlehem, Pennsylvania. He serves as a resident-at-large member on the Editorial Board for AAOS Now.

David Spiegel, MD, FAAOS, is a professor of orthopaedic surgery at the University of Pennsylvania School of Medicine and attending surgeon in the Division of Orthopaedics at Children’s Hospital of Philadelphia.