Usefulness of Procalcitonin in Diagnosing Diabetic Foot Osteomyelitis

A Pilot Study

Venkat N. Vangaveti, PhD; Oliver G. Heyes, MD; Shaurya Jhamb, MD; Nagaraja Haleagrahara, PhD; Usman H. Malabu, MD, FACP, FRACP


Wounds. 2021;33(7):192-196. 

In This Article


Study Design and Participants

This prospective cohort study was carried out at the Townsville University Hospital and Kirwan Community Health Center, both in Kirwan, Australia, comparing biomarkers of patients with diabetic foot osteomyelitis (group 1) and soft tissue infection of the foot (group 2). The study received Institutional Review Board/Independent Ethics Committee/Research Ethics Board approval HREC/17/QTHS/113 & 65. This study was conducted according to the principles of Good Clinical Practice, the declaration of Helsinki, and national laws and regulations regarding clinical studies.

Patients with type 2 diabetes mellitus, aged 18 years or older, who had a moderate or severe infected ulcer based on the Infectious Diseases Society of America classification were included in the study after informed consent was obtained.[9] Patients who had planned surgical intervention, clinically significant lower-extremity ischemia (as defined by an ankle/brachial index of less than 0.65), or ulcer of non-diabetic pathophysiology were excluded from the study. Additional exclusion criteria included other infectious diseases, immunosuppressive therapy, organ and/or hematological malignancies, and end-stage renal disease requiring dialysis.

The bones involved included 3 areas of the foot, namely hindfoot (tarsal bones of calcaneus and talus), midfoot (other tarsals), and forefoot (metatarsals and phalanges). The diagnosis of osteomyelitis was confirmed by positive histopathological examination and culture of bone at the clear surgical margin or as indicated from a percutaneous bone biopsy. In patients who had clinically proven osteomyelitis, antibiotics were administered after obtaining diagnostic blood and tissue samples. The DFO group was defined by intraoperative bone sample showing histologic findings of osteomyelitis, presence of probe-able bone underlying ulcer or by imaging (radiograph, MRI). Clinical history of patients was collected, including age, sex, ethnicity, alcohol and smoking status, medications, comorbidities such as retinopathy, coronary artery disease, and hypertension, and previous amputation.

Laboratory Procedures

Morning fasting venous blood samples were taken for PCT and other inflammatory markers. After 30 minutes of collection, the sample was centrifuged for 12 minutes at 3000 rpm; 0.1 mL of venous plasma was stored at –80°C for analysis as a batch to minimize variance. Serum levels of PCT, interleukin 6 (IL-6), tumor necrosis factor-α, adiponectin, CD253 (TRAIL; Affymetrix eBioscience), osteoprotegerin (OPG; Thermo Fisher Scientific), Dickkopf-related protein 1 (DKK1), osteocalcin, osteopontin (OPN), and sclerostin (Map Human Bone Magnetic Panel; MILLIPLEX) were measured using the ELISA kits as per manufacturer's instructions.

Statistical Analysis

All data were expressed as mean ± SEM. Statistical analysis was performed using SPSS version 25 (IBM Corp). Continuous data were checked for normality followed by a parametric test, Student's t test, or non-parametric Man-Whitney U test to compare the groups. Categorical variables were tested using χ2 test or Fisher's exact test. Receiver operating characteristic curves (ROC) were generated, and the best cutoff point with highest prognostic value presented based on Youden's index was used to determine the diagnostic levels. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte (MLR) ratio, and platelet-to-lymphocyte ratio (PLR) were calculated.[10] The clinical utility index calculator was utilized to compute positive and negative predictive values.[11] A P value of .05 was considered statistically significant.