Patients who have diabetes complicated by any degree of peripheral neuropathy are inherently at an increased risk for developing ulcers and infections. When patients with diabetes present with an ulceration, the degree of severity plays an important role in the need to rule out concomitant osteomyelitis. While many cases are straightforward with respect to which patients require a workup for osteomyelitis, clinicians often see other cases with equivocal findings and chronic non-healing ulcerations that are not as clear-cut. Indeed, a standard for osteomyelitis screening remains elusive when clinical findings are not directive.
Markers of ulcer severity, such as ulcer size, depth (which includes the probe to bone test) and the presence of overt signs of infection (including drainage, ascending lymphangitis, erythema and calor) are all clinical indicators for reasonable suspicion of underlying osteomyelitis. What is important for one to note is that simply the presence of an ulceration as a portal of entry is sufficient for bacterial infiltration and a subsequent osseous infection in a host patient with diabetes. Moreover, certain clinical indicators, such as a new onset of worsening glycemic control or wound deterioration, should trigger rapid investigation.1
When clinical findings are present, subsequent lab tests and imaging can rule in or rule out disease or pathology. Accordingly, one should not think of these diagnostic efforts as screening. For those instances in which no other indication exists other than the continued presence of a stable non-healing ulcer, screening in the high-risk patient is especially justified. Failure to elucidate hidden or subacute osteomyelitis will almost always result in a rapid deterioration with a subsequent risk of sepsis and/or amputation.
Essential Diagnostic Considerations
Duration of ulcer presence is also an important clinical clue to consider. For superficial, clinically non-infected ulcerations, radiographs are important to obtain upon the patient’s initial presentation. This is the case even when no clinical findings support a workup for osteomyelitis. Baseline radiographs can certainly reveal early findings that may support further intervention.2 When initial radiographs do not reveal changes consistent with osteomyelitis, clinicians need to be aware that ulcer persistence can lead to osteomyelitis even when there is no apparent clinical worsening.
For patients who present with chronic, long-standing, non-healing ulcerations, the prolonged nature of the ulcer increases the likelihood for osteomyelitis to develop. In such cases, the need for initial radiographs on presentation is far more pertinent. Chronicity is the single most important indicator toward the decision for obtaining radiographs.
Ample evidence and literature exist in regard to the probe to bone test and its importance in screening for osteomyelitis.1 While this test should be part of any diabetic ulcer evaluation, it is not effective for shallow, non-healing ulcerations without undermining or other signs of deep probing. That said, in regard to the positive and negative predictive values associated with the probe to bone test, clinicians should consider this info in context with the nature of individual cases and presentations.1
Recognizing The Challenges Of Surveillance For Osteomyelitis
When it comes to surveillance testing for any pathology, there are a multitude of factors for clinicians to consider. The effectiveness of any screening test hinges on its ability to detect pathology while being easy to perform in a cost-effective manner. The risks associated with the test should be minimal and the rates of false positives and false negatives must be exceedingly low.
Screening for osteomyelitis is challenging for a variety of reasons. Confounding comorbidities that can coexist with osteomyelitis may influence laboratory tests such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).3 When one has a high index of suspicion for osteomyelitis, these tests can add confirmatory evidence and/or track trends in the efficacy of treatment. While radiographs are a standard modality, the lag in radiographic findings can be misleading and delay treatment. The earliest radiographic signs include periosteal reactions that one typically does not see until seven to 14 days after the onset of osseous infection.3 Accordingly, radiographs are not adequate for early detection of osteomyelitis.
Clinicians have utilized other modalities to diagnose osteomyelitis and they include the three-phase bone scan, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). These modalities, however, all have limitations in screening for bone infection in asymptomatic, clinically non-infected patients.
In my experience, the highest predictive values for osteomyelitis come from a conglomerate of clinical findings, which cumulatively impart high suspicion for a diagnosis of osteomyelitis, thus justifying more judicious use of any of the aforementioned diagnostic modalities. The most important clinical findings to note are the simultaneous existence of a wound surface area greater than two cm2 and a positive probe to bone test. In this scenario, the additional finding of an ESR greater than 70 mm/h increases the likelihood of a positive diagnosis. The algorithm for screening should be to obtain radiographs at this point.3 The likelihood for a positive diagnosis for osteomyelitis doubles when plain radiographs are abnormal after the aforementioned prescreen indicators are also positive.4
When there are clinical findings suggestive for osteomyelitis, one may pursue screening with ESR and radiographs. No single finding in a patient history or physical exam reliably excludes osteomyelitis.
Is There A True Gold Standard For Osteomyelitis Screening?
The single most accurate gold standard for diagnosis remains an antibiotic-free interval bone biopsy.5 While bone biopsy is not a screening test, clinicians may utilize the bone biopsy to confirm an osteomyelitis diagnosis after a screening test is highly indicative of disease.5
The importance of early detection of underlying osteomyelitis is related to the treatments available in the foot. The mainstay modalities include long-term antibiotics, osseous resection of the infected bone(s) or combination therapy. There is significant morbidity associated with both of these modalities and, in many cases, patients go on to have amputations. Therefore, the earlier one can detect osteomyelitis, the less the risk for amputations and other medication-related complications.4
In my experience, it is standard to obtain monthly surveillance radiographs to monitor for osteomyelitis. It remains to be seen if these monthly surveillance radiographs for potential osteomyelitis are cost-effective or confer protective value in terms of reducing operative interventions, amputations or the use of long-term antibiotics. The logic behind this practice is that radiographic findings take two weeks to detect but bimonthly radiographs are likely too frequent.
As long as there are qualitative and quantitative improvements to a preexisting ulceration, one can extend the interval for surveillance radiographs or laboratory testing for osteomyelitis. However, it is important to keep track of the date of the most recent radiographs and document clearly as to the decision to take or not take action toward determining the existence of osteomyelitis. For patients with a history of previous osteomyelitis, I would urge a far more deliberate practice to adhere to monthly (or more frequent if necessary) screening until the offending ulcer(s) completely resolve.
The judicious use and interpretation of laboratory values and imaging modalities are simple and effective ways to understand complex pathologies. The progression of disease and the long-term health consequences of ulcerations complicated with underlying osteomyelitis offer clinicians an opportunity to adequately provide high-level care across time. When clinical findings are obvious, the threshold to diagnose and treat should be extremely low. The thresholds for operative intervention and obtaining bone biopsies should also be extremely low in this high-risk population.
The screening process for osteomyelitis is dynamic and intervals will fluctuate with each patient. Although data is limited with respect to the efficacy of screening, the benefits far outweigh risks associated with lack of detection for these patients.
In short, it is a wise practice to frequently consider whether osteomyelitis screening is prudent for your ulcer patient. One should also develop a screening algorithm for osteomyelitis if you do not already have one in place.
Dr. Elmarsafi is a fellowship-trained foot and ankle surgeon, and an Associate of the American College of Foot and Ankle Surgeons.
1. Aragón‐Sánchez J, Lipsky BA, Lázaro‐ Martínez JL. Diagnosing diabetic foot osteomyelitis: is the combination of probe‐to‐bone test and plain radiography sufficient for high‐risk inpatients? Diabet Med. 2011;28(2):191-194.
2. Butalia S, Palda VA, Sargeant RJ, Detsky AS, Mourad O. Does this patient with diabetes have osteomyelitis of the lower extremity?. JAMA. 2008;299(7):806-813.
3. Crim BE, Wukich DK. Osteomyelitis of the foot and ankle in the diabetic population: diagnosis and treatment. J Diabet Foot Complic. 2010;1(2):26-35.
4. Donegan R, Sumpio B, Blume PA. Charcot foot and ankle with osteomyelitis. Diabet Foot Ankle. 2013. Available at: https:// www.ncbi.nlm.nih.gov/pmc/articles/ PMC3789286/pdf/DFA-4-21361.pdf . Published October 1, 2013. Accessed November 13, 2020.
5. Elamurugan TP, Jagdish S, Kate V, Parija SC. Role of bone biopsy specimen culture in the management of diabetic foot osteomyelitis. Int J Surg. 2011;9(3):214-216.