Making an accurate diagnosis of osteomyelitis in a patient with diabetes is essential in order to minimize complications. Nearly 33 percent of diabetic foot infections develop osteomyelitis. Most of these infections are a result of direct contiguous spread from soft tissue lesions.1
Early diagnosis and antibiotic therapy are important in order to prevent amputation. In healthy patients, acute osteomyelitis does not usually present a diagnostic challenge. This is due to the obvious systemic signs and symptoms such as fever, malaise, pain, tenderness and decreased motion of affected bone.2 However, in diabetic patients with acute osteomyelitis, the common signs and symptoms of infection are often absent.3
In distinguishing chronic osteomyelitis from acute osteomyelitis, Schauwecker noted that chronic osteomyelitis involves greater than one episode of treatment and/or a persistent infection lasting more than six weeks.4 The diagnosis of chronic osteomyelitis is often difficult to make utilizing radiological and nuclear imaging studies since there can be preexisting changes in the osseous architecture from prior trauma or surgery.2
Many published studies have detailed the accuracy of the numerous modalities physicians currently use to diagnose osteomyelitis.5 These modalities include radiography, computed tomography (CT), magnetic resonance imaging (MRI), leukocyte scintigraphy, bone scintigraphy, gallium scintigraphy and combined techniques. The most recent modality is fluorodeoxyglucose positron emission tomography (FDG-PET).
In terms of diagnostic studies, the best imaging modality is one that is both highly sensitive and specific. Several studies have recently reviewed FDG-PET for its ability to diagnose osteomyelitis accurately.2 The results indicate that FDG-PET may be the most sensitive and specific imaging modality currently available to determine the presence or absence of osteomyelitis. Most importantly for podiatrists, it may be more helpful than other modalities in differentiating Charcot neuroarthropathy from osteomyelitis in patients with diabetes.
Dinh and colleagues performed a meta-analysis to determine the pooled sensitivity and specificity of radiography, MRI, bone scan and leukocyte scan for the diagnosis of osteomyelitis.6 They found that the pooled sensitivity for radiography was 54 percent and pooled specificity was 68 percent. Changes on radiographs were not evident until 40 to 70 percent of the bone had been resorbed, reducing the sensitivity in the initial two to four weeks of the infection. Pooled sensitivity for MRI was 90 percent and pooled specificity was 79 percent. Pooled sensitivity for bone scan was 81 percent and pooled specificity was 28 percent. Pooled sensitivity for leukocyte scan was 74 percent and pooled specificity was 68 percent.
In their meta-analysis, Termaat and co-workers found that a combined bone and leukocyte scan has a pooled sensitivity of 78 percent and a pooled specificity of 84 percent.5 Out of the aforementioned modalities, researchers found that MRI was the most accurate at diagnosing osteomyelitis.6,7
The 18F-fluorodeoxyglucose (FDG) is a radiolabeled glucose analog. The FDG-PET was originally in use for the diagnosis of neoplastic disorders but has now expanded to include the diagnosis of different inflammatory conditions. There is an increased uptake of FDG in activated inflammatory cells like macrophages and lymphocytes. This is caused by significantly increased levels of glycolysis due to an increase in
the number of cell surface glucose transporters from cytokine cell stimulation.2 Various studies have assessed the accuracy of the FDG-PET at diagnosing osteomyelitis.
De Winter and colleagues performed a prospective study using FDG-PET scans on 60 patients suspected of having chronic infections involving the axial and appendicular skeleton.8 Two experienced, unbiased radiologists read the scans independently. The final diagnosis was based on histology and bacterial cultures in 18 patients and clinical findings with a minimum follow-up of six months in 42 patients.
The researchers determined that 25 patients were infected with osteomyelitis being identified correctly by both radiologists.8 There were four false positives. The sensitivity for the group with appendicular skeletal infections was 100 percent and the specificity was 86 percent. These authors determined that the PET scan is highly accurate at diagnosing chronic osteomyelitis and could become the standard imaging technique for this condition.
Basu and co-workers conducted a prospective clinical trial comparing the use of PET scan to MRI in diabetic feet complicated by acute Charcot neuroarthropathy.9 The authors wanted to discover if PET could distinguish between Charcot osteoarthropathy and osteomyelitis. The patients were divided into four groups: 17 patients with Charcot neuroarthropathy, 21 patients with uncomplicated diabetic feet, 20 non-diabetic patients with normal lower extremities and five patients with osteomyelitis secondary to complicated diabetic feet.
Even in the presence of Charcot and coexisting foot ulcers, the PET scan accurately ruled out osteomyelitis.9 Charcot joints had small amounts of diffuse uptake of FDG. The PET had 100 percent sensitivity and 93.8 percent accuracy in the diagnosis of Charcot foot in this study. In contrast, MRI was 76.9 percent sensitive and 75 percent accurate.
In their meta-analysis comparing different imaging modalities for the diagnosis of chronic osteomyelitis, Termaat and colleagues concluded that FDG-PET had the highest accuracy in confirming or excluding the diagnosis of chronic osteomyelitis with a pooled sensitivity of 96 percent and a pooled specificity of 91 percent.5 However, they noted that due to the limited availability of PET, one can use combined bone and leukocyte scintigraphy with satisfactory accuracy to diagnose chronic osteomyelitis in the appendicular skeleton.
In comparison to other nuclear imaging modalities, FDG-PET has the advantage of being able to provide results within two hours.10 Bone scans stay positive for a long time after a fracture but the uptake of FDG usually normalizes after two to three months following a fracture, making it useful in evaluating chronic osteomyelitis with previous trauma.2,11,12
In comparison to imaging modalities such as CT, MRI and ultrasound, FDG-PET is advantageous because it offers full body coverage, high sensitivity, an absence of artifacts from metallic hardware and a lack of reactions to pharmaceuticals.2 Unlike WBC scans, FTG-PET is highly sensitive for osteomyelitis in patients who have taken antibiotics before imaging.13
While it is well documented that hyperglycemia can adversely affect FTG-PET scan results when physicians use them to detect neoplasms, Zhuang and co-workers concluded that mild to moderate hyperglycemia (<250 mg/dl) does not appear to adversely affect the results when one uses the scan to detect inflammation.14
The disadvantages of FDG-PET include its limited availability and high cost.5 Additionally, 18F-FDG has a half-life that is not very long (110 minutes) so one must schedule patients very strategically throughout the day.15
Another issue with FDG-PET is the fact that it has a comparably low spatial resolution when one measures this against other techniques such as CT. Fortunately, physicians can overcome this with the combined modality FDG-PET/CT.16
Keidar and colleagues studied osteomyelitis in 18 suspected infection sites in 14 patients with diabetes, and used FDG-PET/CT.17 The PET scans alone may not be able to clearly identify the location of an area of increased 18F-FDG uptake. The FDG-PET/CT is a hybrid technology that combines the sensitivity of PET with the ability of CT to determine the exact anatomic location of infections.18
Keidar and co-workers found that FDG-PET/CT was able to correctly differentiate osteomyelitis from soft tissue infections in all sites.17 The complicated diabetic foot is a specific scenario that may benefit substantially from hybrid imaging modalities. The use of these combined techniques will lead to the avoidance of unnecessary and expensive invasive procedures.19
Although MRI and nuclear medicine scans are effective modalities for diagnosing osteomyelitis, recent studies have proven that PET scans are more effective in accurately diagnosing osteomyelitis. In their meta-analysis, Termaat and colleagues concluded that further studies, including randomized clinical trials, are needed to assess the true ability of FDG-PET scan to diagnose osteomyelitis.5
Despite promising results from these studies, FDG-PET is still not being utilized routinely in clinical practice. Its high cost and limited availability prevent its widespread use in diagnosing osteomyelitis. In the future, FDG-PET may be especially useful in helping to diagnose osteomyelitis in patients with diabetes whose conditions are complicated by Charcot neuroarthropathy.
The authors acknowledge Gavin Duke, MD, who is affiliated with East River Medical Imaging in New York City, for generously allowing them to view his PET/CT images. They also thank Anthony Iorio, DPM, Assistant Dean for Continuing Medical Education at the New York College of Podiatric Medicine, for his help in obtaining the PET/CT images and fourth-year student John Schwerdt for his help in researching the topic.
Ms. Markowitz is a third-year student at the New York College of Podiatric Medicine.
Mr. Kantor is a third-year student at the New York College of Podiatric Medicine.
Dr. Cohen is a Professor and Director in the Radiology Section in the Department of Medical Sciences at the New York College of Podiatric Medicine.
Dr. Khan is an Assistant Professor in the Department of Medical Sciences at the New York College of Podiatric Medicine. He is an Associate of the American College of Foot and Ankle Surgeons, and a Fellow of the American Professional Wound Care Association.
Dr. Steinberg is an Assistant Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C. Dr. Steinberg is a Fellow of the American College of Foot and Ankle Surgeons.
1. Lipsky BA. A report from the international consensus on diagnosing and treating the infected diabetic foot. Diabetes Metab. Res. Rev 2004; 20 (Suppl. 1): S68-S77.
2. Kumar R, Basu S, Torigian D, et al. Role of modern imaging techniques for the diagnosis of infection in the era of 18 F- Fluorodeoxyglucose positron emission tomography. Clin Microb Rev 2008; 21(1):209-224.
3. Schinabeck MK, Johnson JL. Osteomyelitis in diabetic foot ulcers. Prompt diagnosis can avert amputation. Postgrad Med 2005; 118(1):11-15.
4. Schauwecker DS. Osteomyelitis: diagnosis with In-111-labeled leukocytes. Radiology 1989; 171(1):141-146.
5. Termaat MF, Rajimakers PGHM, Scholten HJ, et al. The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: A systematic review and meta analysis. JBJS Am 2005; 87(11):2464-2471.
6. Dinh MT, Abad CL, Safdar N. Diagnostic accuracy of physical examination and imaging tests for osteomyelitis underlying diabetic foot ulcers: meta analysis. Clin Infect Dis 2008; 47(4):519-527.
7. Jeffcoate WJ, Lipsky BA. Controversies in diagnosing and managing osteomyelitis of the foot in diabetes. Clin Infect Dis 2004; 39(Suppl 2):S115-122.
8. De Winter F, van de Wiele C, Vogelaers D, et al. Flourine-28 Fluorodeoxyglucose-positron emission tomography: a highly accurate imaging modality for the diagnosis of chronic musculoskeletal infections. JBJS 2001; 83-A(5):651-660.
9. Basu S, Chryssicos T, Houseni M, et al. Potential role of the FDG PET in the setting of diabetic neuro-osteoarthropathy: can it differentiate uncomplicated Charcot’s neuroarthropathy from osteomyelitis and soft tissue infection? Nucl Med Commun 2007; 28(6):465-472.
10. De Winter F, Vogelaers D, Gemmel F, et al. Promising role of 18-F-flouro-D-deoxyglucose positron emission tomography in clinical infectious diseases. Eur J Clin Microb Infect Dis 2002; 21(4):247-257.
11. Zhuang H, Sam JW, Chacko TK, et al. Rapid normalization of osseous FDG uptake following traumatic or surgical fractures. Eur J Nucl Med Mol Imaging 2003; 30(8):1096-1103.
12. Hartmann A, Eid K, Dora C, et al. Diagnostic value of (18)F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis. Eur J Nucl Med Mol Imaging 2006; 34(5):704-714.
13. Zhuang H, Duarte PS, Pourdehand M, et al. Exclusion of chronic osteomyelitis with F-18 flourodeoxyglucose positron emission tomographic imaging. Clin Nucl Med 2000; 25(4):281-284.
14. Zhuang H, Cortes-Blanco A, Pourdehand M, et al. Do high glucose levels have differential effect on FDG uptake in inflammatory and malignant disorders? Nucl Med Commun 2001; 22(10):1123-1128.
15. Khan N, Oriuchi N, Higuchi T, et al. Review of FDG-PET: The FDG-PET imaging protocol. Cancer Control 2005; 12(4):254-260
16. Basu S, Chryssikos T, Moghadam-Kia S, et al. Positron emission tomography as a diagnostic tool in infection: Present role and future posibilities. Semin Nucl Med 2009; 39(1):36-51.
17. Keidar Z, Militianu D, Melamed E, Bar Shalom R, Israel O. The diabetic foot: Initial experience with 18F-FDG PET/CT. J Nucl Med 2005; 46(3):444-449.
18. Israel O, Keidar Z, Iosilevsky G, et al. The fusion of anatomic and physiologic imaging in the management of patients with cancer. Semin Nucl Med 2001; 31(3):191-205.
19. Nawaza A, Torigian DA, Siegelman ES, et al. Diagnostic performance of FDG-PET, MRI, and plain film radiography (PFR) for the diagnosis of osteomyelitis in the diabetic foot. Mol Imaging Biol 2009. Epub ahead of print.
20. Lipsky BA. Osteomyelitis of the foot in diabetic patients. Clin Infect Dis 1997; 25(6):1318-1326.