Can Chronic Osteomyelitis Have Negative Pathology Results from Bone Specimens?
Yes, chronic osteomyelitis can absolutely have negative pathology results from bone specimens, and this occurs due to sampling errors, prior antibiotic therapy, or failure to isolate fastidious organisms. 1
Why Bone Specimens Can Be Falsely Negative
Both culture and histopathology from bone specimens may be falsely negative in chronic osteomyelitis. The International Working Group on the Diabetic Foot explicitly states that bone histopathology may be falsely negative because of sampling error, and bone cultures may be falsely negative due to sampling errors, prior antibiotic therapy, or failure to isolate fastidious organisms. 1
Key Mechanisms of False-Negative Results:
Sampling error: Even with fluoroscopic or CT guidance, the biopsy needle may miss the area of active osteomyelitis, particularly in heterogeneous infections 1
Prior antibiotic exposure: Recent antimicrobial therapy significantly reduces culture yield, though data from vertebral osteomyelitis suggests at least half of bone cultures remain positive even with pretreatment 1
Fastidious organisms: Some pathogens are difficult to isolate with standard culture techniques 1
Technical factors: Inadequate specimen processing or insufficient tissue sampling can lead to negative results 2
Clinical Evidence of False-Negative Bone Specimens
A compelling case from the Society of Academic Bone Radiologists demonstrates this phenomenon: A 52-year-old patient with MRI-confirmed osteomyelitis had a positive wound culture growing Staphylococcus aureus, but the subsequent intraoperative bone culture was negative despite positive bone pathology for osteomyelitis. 1 This case illustrates that preceding antibiotic treatment can render bone cultures negative even when histopathology confirms active infection.
Strategies to Minimize False-Negative Results
To reduce the likelihood of false negatives, impose an antibiotic-free period of ideally 2 weeks (but even a couple of days may be helpful) in clinically stable patients before performing bone biopsy. 1, 3 This is safe in chronic osteomyelitis without substantial soft tissue infection, as it is typically a slowly progressive disease. 1
Additional Technical Recommendations:
Use image guidance: Perform bone biopsy using fluoroscopic or CT guidance to improve sampling accuracy 1
Proper specimen handling: Process bone specimens for both culture and histopathology, as one may be positive when the other is negative 1
Adequate tissue sampling: Obtain sufficient bone core material rather than superficial samples 2
Histopathology Findings in Chronic Osteomyelitis
Chronic osteomyelitis on histopathology is characterized by destroyed bone and infiltration of lymphocytes, histiocytes, or plasma cells, in contrast to acute osteomyelitis which shows necrosis and polymorphonuclear granulocytes. 1 However, histopathology can be falsely negative due to sampling error or falsely positive in patients with non-infectious inflammatory disorders. 1
Clinical Implications
Despite the possibility of false-negative results, bone biopsy remains the gold standard for diagnosing osteomyelitis, as it provides the most reliable data on causative organisms and antimicrobial susceptibility. 1, 3 The overall culture positivity rate from bone specimens is approximately 50-94%, depending on the study and clinical context. 2, 4
When bone biopsy results are negative but clinical suspicion remains high based on imaging (particularly MRI) and clinical findings, treatment should proceed as presumed staphylococcal infection with standard duration therapy. 3 The diagnosis should incorporate combinations of clinical, radiologic, and biologic parameters rather than relying solely on bone culture or histopathology results. 1