Can bone become inflamed (osteitis, periostitis, or osteomyelitis) and how should I evaluate and manage a patient with new‑onset bone pain without an obvious fracture?

Can Bone Become Inflamed?

Yes, bone can absolutely become inflamed through several distinct pathological processes: osteitis (inflammation of bone), periostitis (inflammation of the periosteum), and osteomyelitis (bone infection with inflammation). 1

Types of Bone Inflammation

Osteomyelitis (Infectious)

• Osteomyelitis is a chronic inflammatory disease induced by bone infection that may involve marrow, cortex, periosteum, and adjacent soft tissues, persisting for weeks, months, or years. 2, 3
• The infection breaches anatomical and immunological barriers, with bone becoming the primary nidus that continuously sheds debris into adjacent tissues. 1
• In stage IV pressure injuries, osteomyelitis prevalence ranges from 17% to 58%, demonstrating that exposed bone alone does not equal infection. 1

Periostitis (Periosteal Inflammation)

• Periostitis represents inflammation of the periosteum with reactive new bone formation, visible radiographically as periosteal reaction or "onion skin" appearance. 4, 5, 6
• Periostitis ossificans (Garré osteomyelitis) is a non-suppurative chronic osteomyelitis primarily affecting children and adolescents, most commonly in the mandible. 5, 6
• Reactive periosteal changes can occur without infection—pressure-related bone changes including reactive bone formation and bone marrow edema are observed in all stage IV pressure injuries regardless of osteomyelitis presence. 1

Chronic Non-Bacterial Osteitis (Autoimmune)

• Chronic non-bacterial osteitis (CNO) is an autoinflammatory bone disease characterized by sterile bone inflammation, often requiring immunosuppressive rather than antibiotic therapy. 1, 4
• CNO typically presents with bone marrow edema, osteolysis, and periosteal reaction in characteristic locations (anterior chest wall, spine, mandible) without infectious etiology. 1

Evaluation of New-Onset Bone Pain Without Obvious Fracture

Initial Clinical Assessment

Physical examination findings that increase likelihood of osteomyelitis:

• Visible or palpable bone through a wound (positive likelihood ratio 9.2) 1, 7
• "Sausage toe" appearance—swollen, erythematous digit lacking normal contour 7
• Ulcer area >2 cm² (positive likelihood ratio 7.2) 7
• Non-healing ulcer despite 6 weeks of appropriate care and off-loading 7
• Purulent drainage from wounds overlying bone 1

Perform probe-to-bone test on any ulcer present:

• A positive test (hard, gritty sensation) yields a positive likelihood ratio of 9.2 in high-risk patients with clinically infected wounds. 7
• A negative test does not rule out osteomyelitis and should not preclude further evaluation. 7

Important caveat: Clinical examination alone has low sensitivity (22–33%) for diagnosing osteomyelitis, particularly in pelvic/pressure injury contexts. 1

Laboratory Markers

• Inflammatory markers (ESR, CRP) are non-specific and elevated due to multiple factors in patients with wounds or pressure injuries, rendering them not particularly useful for diagnosing osteomyelitis. 1
• ESR >70 mm/h provides a likelihood ratio of 11 for osteomyelitis when combined with clinical findings. 7
• White blood cell count is not predictive of osteomyelitis. 7

Imaging Algorithm

Step 1: Plain Radiographs (Always First)

• Obtain plain X-rays in all suspected cases to exclude fracture, tumor, degenerative changes, foreign bodies, or soft-tissue gas. 1, 7, 8
• Radiographs are typically normal in the first 7–10 days and only reveal abnormalities after >30% bone loss. 1, 7, 8
• Acute findings (when present): periosteal reaction, well-circumscribed focal lucency, frank bone destruction, soft-tissue swelling. 1, 8
• Chronic findings: mixed lucency and sclerosis, sequestra, cortical erosions, trabecular coarsening. 1

Critical pitfall: Normal radiographs do not exclude osteomyelitis, especially in early presentation—sensitivity is extremely low until significant bone destruction occurs. 1, 7, 8

Step 2: MRI with IV Contrast (Gold Standard)

• If osteomyelitis is suspected but radiographs are normal or equivocal, proceed directly to MRI—do not delay 2–4 weeks waiting for repeat X-rays. 1, 7, 9
• MRI demonstrates 90–98% sensitivity, 22–98% specificity, and 100% negative predictive value for excluding osteomyelitis. 1
• MRI detects bone marrow edema (the earliest pathological feature), cortical disruption, soft-tissue inflammation, sinus tracts, and abscess formation before any radiographic abnormality appears. 1, 7
• Modern metal artifact reduction techniques significantly improve evaluation of hardware-associated infections. 9

MRI limitations:

• Low specificity in some contexts because bone marrow edema and reactive changes occur in pressure injuries, trauma, and other non-infectious conditions. 1
• Cannot reliably distinguish infection from reactive inflammation in all cases. 1

Step 3: Alternative Advanced Imaging (When MRI Contraindicated or Equivocal)

• ^18^F-FDG PET/CT (if surgery occurred >6 months ago): sensitivity 83–100%, specificity 76–100% for post-traumatic osteomyelitis with hardware. 7, 9
• Combined white-blood-cell-labeled scan with bone-marrow imaging when MRI unavailable. 7
• Avoid: Three-phase bone scan alone (specificity ≈25% in chronic osteomyelitis), leukocyte scan alone (sensitivity 21–74%), CT without contrast. 7, 9

CT has limited role but useful for:

• Visualizing sequestra, cortical destruction, sinus tracts, soft-tissue gas, and foreign bodies. 1, 7
• Better spatial resolution than MRI for detecting early bone abnormalities in some contexts. 1

Definitive Diagnosis

Bone biopsy (culture + histopathology) is the gold standard:

• Histopathology shows infiltration of polymorphonuclear cells (acute) or mononuclear cells (chronic) within bone marrow tissue. 1
• Intraoperative excisional bone biopsy during debridement is preferred because osteomyelitis can be focal and core needle biopsies may miss infected regions. 1
• Bone cultures demonstrate high sensitivity (76–100%) but low specificity (8–67%); experts recommend combining microbiological and histological criteria. 1

Indications for bone biopsy:

• Diagnostic uncertainty after imaging 7
• Soft-tissue cultures suggesting resistant organisms 7
• Progressive bony deterioration or persistently elevated inflammatory markers during therapy 7
• Failure of empiric antibiotics 7
• Planned use of high-risk antibiotics (rifampin, fluoroquinolones) 7
• When bone will receive orthopedic hardware 7

Critical caveat: Perform bone biopsy before initiating antimicrobial therapy to maximize culture yield. 7

Do not use soft-tissue or sinus-tract cultures to guide antibiotic selection—they do not reliably reflect bone pathogens. 7

Management Principles

Surgical Treatment

• Eradication of infection requires resection of affected bone segments and soft tissue, followed by reconstructive methods. 2
• Chronic osteomyelitis with hardware and sinus tracts typically requires hardware removal, extensive debridement, prolonged antibiotic therapy, and possible staged reconstruction. 9
• If POM is left untreated, multifocal bone involvement occurs with formation of additional draining tracts. 1

Antimicrobial Therapy

• Empiric regimens must target Staphylococcus aureus (≈50% of cases), coagulase-negative staphylococci (≈25%), aerobic streptococci (≈30%), and Enterobacteriaceae (≈40%). 7
• Long-term suppressive antibiotic therapy may be a reasonable alternative to surgery in inoperable situations, but consider risks of side effects, resistant organism selection, cost, and quality of life. 3

Special Considerations for Non-Bacterial Osteitis

• When cases lack obvious infectious source and fail antibiotic therapy, consider immunologically mediated etiology (primary chronic osteomyelitis or chronic recurrent multifocal osteomyelitis). 1, 4
• Immunosuppressive therapy (TNF inhibitors, corticosteroids, methotrexate) may be effective for resilient cases with autoimmune mechanisms. 4

Differential Diagnosis to Exclude

When evaluating bone pain without fracture, systematically exclude:

• Infectious osteomyelitis (fever, chills, presumable port of entry, bacteremia) 1
• Malignant bone tumor (weight loss, solitary lesion with quick growth, cortical destruction) 1
• Psoriatic arthritis (psoriasis, inflammatory arthritis, nail dystrophy, dactylitis) 1
• Axial spondyloarthritis (inflammatory back pain, sacroiliitis, HLA-B27 positivity) 1
• Paget's disease (family history, pelvic/skull location, elevated alkaline phosphatase, age >50 years) 1
• Osteomalacia (generalized bone pain, muscle weakness, low vitamin D, bone demineralization) 1

1, 7, 8, 9, 2, 3, 4, 5, 6