Archives of Academic Emergency Medicine. 2020; 8(1): e71

OR I G I N A L RE S E A RC H

Diagnostic Value of Erythrocyte Sedimentation Rate and C
Reactive Protein in detecting Diabetic Foot Osteomyelitis;
a Cross-sectional Study
Seyed Kaveh Moallemi1, Mahtab Niroomand2, Niki Tadayon3, Mohammad Mehdi Forouzanfar4, Alireza
Fatemi5∗

1. AJA University of Medical Sciences, Tehran, Iran.

2. Division of Endocrinology, Department of Internal Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3. Surgery Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4. Emergency Department, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5. Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Received: June 2020; Accepted: August 2020; Published online: 8 September 2020

Abstract: Introduction: Osteomyelitis is one of the complications of diabetic foot infection. The present study aimed
to evaluate the diagnostic value of erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) in detec-
tion of osteomyelitis in patients with diabetic foot. Methods: In this cross-sectional study, serum levels of ESR
and CRP were measured for patients with diabetic foot referring to emergency department or endocrinology
clinic and the screening performance characteristics of these markers in detection of osteomyelitis were calcu-
lated. The diagnosis of osteomyelitis was based on clinical examination and positive probe-to-bone test, which
was confirmed by plain x-rays or MRI. Results: 142 diabetic patients with an average age of 61.2 ± 11.8 years
were evaluated (66.2% male). The area under the ROC curve of ESR in detection of osteomyelitis in diabetic
foot cases was 0.70 (95% CI: 0.62-0.79). The best ESR cut-off point in this regard was 49 mm/hour. Sensitiv-
ity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of ESR in 49
mm/Hour cut-point were 74.6% (95% CI: 62.9-83.9), 57.7% (95% CI: 45.5-69.2), 63.9% (95% CI: 52.5-73.9), 69.5%
(95% CI: 56.0-80.0), 1.8 (95% CI: 1.3-2.4) and 0.4 (95% CI: 0.3-0.7), respectively. The area under the ROC curve
of CRP in detection of osteomyelitis was 0.67 (95% CI: 0.58-0.76). The best cut-off point for CRP in this regard
was 35 mg/liter with sensitivity, specificity, positive and negative predictive values, and positive and negative
likelihood ratios of 76% (95% CI: 64.2-85), 54.9% (95% CI: 42.7-66.6), 62.8% (95% CI: 51.6-72.8), 69.6% (95% CI:
51.7-80.8), 1.7 (95% CI, 1.3-2.2), and 0.4 (95% CI: 0.3-0.7), respectively. Conclusion: Based on the findings of
ROC curve analysis, ESR and CRP had fair and poor accuracy, respectively, in detecting the diabetic foot cases
with osteomyelitis.

Keywords: C-reactive protein; Diabetic foot; Blood Sedimentation; Osteomyelitis

Cite this article as: Moallemi S K, Niroomand M, Tadayon N, Forouzanfar M M, Fatemi A. Diagnostic Value of Erythrocyte Sedimentation Rate and C Reactive
Protein in detecting Diabetic Foot Osteomyelitis; a Cross-sectional Study. Arch Acad Emerg Med. 2020; 8(1): e71.

1. Introduction

More than 50% of non-traumatic amputations in the United

States are lower-extremity amputations due to diabetes mel-

litus (1). About 5% of diabetic persons are facing foot ulcers

∗Corresponding Author: Alireza Fatemi; Men’s Health and Reproductive
Health Research Center, Shohadaye Tajrish Hospital, Shahrdary Avenue, Tajr-
ish Square, Tehran, Iran. Phone: 00989128949858, Fax: 00982122719014,
Email: alireza.fatemi.md@gmail.com.

each year and treatment of foot ulcers accounts for 15-25%

of total health care processes for diabetes (2, 3). Chronic and

deep wounds can get complicated by osteomyelitis as a con-

sequence of contiguous spread of the microorganisms from

soft tissues to periosteum, and that is the main cause of am-

putation in the majority of these patients (4). Timely diag-

nosis of osteomyelitis is important for preventing migration

of the infection, and delay in osteomyelitis wound treatment

leads to recurrent foot ulcers, increases the likelihood of need

for surgical intervention and amputation, and elongates the

This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).
Downloaded from: http://journals.sbmu.ac.ir/aaem



S K. Moallemi et al. 2

duration of antibiotic therapy (5, 6). Several different op-

tions, including computed tomography (CT) scan, magnetic

resonance imaging (MRI), and triple-phase bone scans, with

different degrees of sensitivity and specificity, have been in-

troduced for use in diagnosis of osteomyelitis (7), but some

studies have revealed that such imaging modalities were not

cost-effective and, therefore, suggested that clinical signs of

infection coupled with the findings of the wound probing to

bone can be much more cost-effective for this purpose (8).

Increased serum inflammatory markers such as White blood

cells (WBCs), C-reactive protein (CRP), and erythrocyte sed-

imentation rate (ESR) have been proposed to aid in diagno-

sis of osteomyelitis. However, in patients with diabetes, their

value in the presence of infection has been questioned (9,

10). The aim of this study was to determine the diagnostic

accuracy of ESR and CRP in detection of diabetic foot cases

with osteomyelitis.

2. Methods

2.1. Study design and setting

In this cross-sectional study, after receiving the ethics ap-

proval (ethics code: IR.SBMU.RETECH.REC.1396.540) and

patient informed consent, all patients who met the Ameri-

can Diabetes Association Criteria (11) for diagnosis of dia-

betes mellitus and had diabetic foot, and had presented to

the emergency department or endocrinology clinic of Shoha-

daye Tajrish Hospital, Tehran, Iran, from April 2018 to 2019

were evaluated.

2.2. Participants

Using convenience sampling, all >18 years old patients with

diabetic foot were enrolled. Patients were excluded if they

had any other concurrent infections, non-infectious inflam-

matory disease, or rheumatologic diseases. Patients who re-

ceived immunosuppressive therapy and pregnant cases were

also excluded.

2.3. Data gathering

Using a predefined checklist, age, gender, leukocyte count,

serum level of ESR or CRP, the characteristics of the wound

(bone visibility, positive probe test, dactylitis, wounds re-

maining more than four weeks, or septic secretions for more

than two weeks), as well as presence or absence of os-

teomyelitis were registered for all cases. The diagnosis of os-

teomyelitis was based on clinical examination and positive

probe-to-bone test and it was confirmed by plain X-rays or

MRI (6).

Six milliliter of peripheral blood sample was drawn from

each individual and inserted into a vial containing Ethylene-

diamine Tetraacetic ethylenediaminetetraacetic acid (EDTA)

anticoagulant. Blood samples were collected under asep-

tic conditions from an antecubital vein for determination

of white blood cell (WBC) count and ESR using the modi-

fied Westergren method. Serum CRP was measured using

BN ProSpec System (Siemens Healthcare Diagnostic Prod-

ucts GmbH, Marburg, Germany; inter- and intra-assay coef-

ficient of variation <4%).

2.4. Statistical Analysis

Data were analyzed using Statistical Package for the Social

Sciences (SPSS) version 16 (SPSS Inc. Chicago, IL) for Win-

dows. Data were presented as mean ± standard deviation
or frequency and percentage. The area under the receiver

operating characteristic (ROC) curve was used to deter-

mine the best cut-off point of studied markers in detecting

osteomyelitis. P value of less than 0.05 was considered statis-

tically significant. Accuracy of 90% - 100% was considered as

excellent, 80% – 90% as good, 70% – 80% as fair, 60% – 70%

as poor and < 60% as fail.

3. Results

3.1. Baseline characteristics of studied cases

A total of 142 diabetic patients with an average age of 61.2 ±
11.8 years were evaluated (66.2 % male). The diagnosis of os-

teomyelitis was confirmed for 71 (50.0%) cases. The mean

age of patients with and without osteomyelitis was 59.7 ±
11.5 and 62.7 ± 11.9 years, respectively (p = 0.12). Table 1
compares the baseline characteristics of patients with and

without osteomyelitis. The frequency of open wound during

the previous 4 weeks (64.8%; p = 0.03), presence of discharge

during the last 2 weeks (47.9%; p <0.0001), and the prevalence

of smoking (28.2%; p = 0.02) were significantly higher in os-

teomyelitis cases. Serum ESR levels were 71.2 ± 29.8 and 50.8
± 24.5 (mm/ hour) in cases with and without osteomyelitis,
respectively (p < 0.0001). These measures were 65.8 ± 37.2
and 43.6 ± 33.0 (mg/liter), respectively, for CRP level (p =
0.0002). The number of white blood cells was significantly

higher in the osteomyelitis group (p = 0.005).

3.2. The diagnostic values of ESR and CRP

Area under the ROC curve of ESR in detection of osteomyeli-

tis in diabetic foot cases was 0.70 (95% CI: 0.62-0.79; figure 1).

The best ESR cut-off point in this regard was 49 mm/hour.

The sensitivity, specificity, positive and negative predictive

values, and positive and negative likelihood ratios of ESR in

49 mm/Hour cut-point were 74.6% (95% CI: 62.9-83.9), 57.7%

(95% CI: 45.5-69.2), 63.9% (95% CI: 52.5-73.9), 69.5 % (95% CI:

56.0-80.0), 1.8 (95% CI: 1.3-2.4) and 0.4 (95% CI: 0.3-0.7), re-

spectively.

Area under the ROC curve of CRP in detection of osteomyeli-

tis was 0.67 (95% CI: 0.58-0.76; figure 1). The best cut-off

This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).
Downloaded from: http://journals.sbmu.ac.ir/aaem



3 Archives of Academic Emergency Medicine. 2020; 8(1): e71

Table 1: Comparing the characteristics of studied patients between cases with and without osteomyelitis

Variables
Suffering from osteomyelitis

P
Without n = 71 With n = 71

Smoking 9(12.7%) 20(28.2%) 0.02
Open wound in last 4 weeks 33(46.5%) 46(64.8%) 0.03
Discharge during last 2 weeks 7(9.9%) 34(47.9%) < 0.0001
Visible bone 0(0%) 2(2.8%) 0.49
Atherosclerosis 35(49.3%) 31(43.7%) 0.50
Hypertension 36(50.7%) 40(56.3%) 0.50
Hyperlipidemia 15(21.1%) 20(28.2%) 0.33
Data are presented based on frequency (%).

Figure 1: The area under the receiver operating characteristic (ROC) curve of erythrocyte sedimentation rate (left) and C reactive protein

(right) in detecting the diabetic foot cases with osteomyelitis.

point for CRP in this regard was 35 mg/liter with sensitivity,

specificity, positive and negative predictive values, and pos-

itive and negative likelihood ratios of 76% (95% CI: 64.2-85),

54.9% (95% CI: 42.7-66.6), 62.8% (95% CI: 51.6-72.8), 69.6%

(95% CI: 51.7-80.8), 1.7 (95% CI, 1.3-2.2), and 0.4 (95% CI: 0.3-

0.7), respectively.

4. Discussion

Based on the findings of ROC curve analysis the ESR and

CRP had fair and poor accuracy, respectively, in detecting

diabetic foot cases with osteomyelitis. An infected bone in

patients with diabetic foot ulcers causes major clinical com-

plication and increases the risk of surgical procedures and

lower extremity amputations and also increases the proba-

bility of treatment outcomes like antibiotic resistance, kid-

ney injury and catheter-related adverse events, which limit

options for treatment and therapy and worsen the prognosis

for cure (12-14). In spite of these potentially devastating con-

sequences, most treatment options are based on experience

and advice, due to lack of high-quality evidence. The find-

ings of this study showed that the predictive value of ESR and

CRP in detecting osteomyelitis is desirable. The sensitivity

and specificity for ESR and CRP were 74.6%, 57.7% and 76%,

54.9%, respectively. The value of each of these biomarkers is

significantly less than MRI.

Kaleta et al. (15) found that erythrocyte sedimentation rate

was significantly higher in the presence of underlying bone

infections. In addition, they determined the optimal cut-off

value with the highest positive and negative predictive val-

ues as 70 mm/h. These finding confirm the role of ESR in

prediction of osteomyelitis in diabetic patients; however, the

best ESR cut-off point to predict osteomyelitis, was 49 mm

per hour in the current study.

Most previously published studies have failed to assess the

relationship between ESR and presence of osteomyelitis or

have not specifically studied its use in the diabetic popula-

tion, while many of them have stated that elevation in ESR is

a predictor of the presence of osteomyelitis (16-18).

The results of Asten et al. study suggested a predictive role

for both ESR and CRP at the time of monitoring the success

of therapy in diabetic foot osteomyelitis (12). The sensitivity

This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).
Downloaded from: http://journals.sbmu.ac.ir/aaem



S K. Moallemi et al. 4

and specificity of CRP (cut-off value >14 mg/L) in diagnosis of

osteomyelitis were 0.85 and 0.83. These values were 0.84 and

0.75 for ESR (cut-off value > 67 mm/h), 0.75 and 0.79 for WBC

(cut-off value >14 × 109/L), and 0.81 and 0.71 for PCT (cut-
off value >0.30 ng/mL), respectively, in Michail et al. study

(2). Although there are some differences in values, but that

study, like the present study, showed that serum inflamma-

tory markers including CRP, ESR and WBC could be used for

the diagnosis of foot infections in patients with diabetes.

Based on the Oktay YapÄścÄś et al. study (19), neutrophil-

to-lymphocyte ratio, CRP, and ESR have a predictive value

for development of osteomyelitis and progression to ampu-

tation in patients with diabetic foot osteomyelitis. As can be

seen, all of the mentioned studies have reported a significant

relationship between inflammatory markers and osteomyeli-

tis. However, the reported diagnostic values for these mark-

ers vary between studies, with sensitivity ranging from 75%

to 90% and specificity ranging from 70% to 80%.

The findings of this study showed that on average, the values

of all inflammatory markers, including ESR and CRP, show an

increase in patients with diabetic foot infections and higher

values were found in patients with osteomyelitis.

5. Limitations

Limitations of this investigation include the small number of

cases reviewed. In future investigations, a prospective evalu-

ation, in which all patients with osteomyelitis are confirmed

with pathology, would improve the value of the study. In ad-

dition, the authors did not correlate location of the bone in-

volvement with laboratory values. It may prove that the pres-

ence of infection in highly vascular areas of the foot or body

may affect the sedimentation rate.

6. Conclusion

Based on the findings of ROC curve analysis, ESR and CRP

had fair and poor accuracy, respectively, in detecting the dia-

betic foot cases with osteomyelitis.

7. Declarations

7.1. Acknowledgements

Hereby, we thank the staff members of Shohadaye Tajrish

Hospital for their hearty cooperation and helping us perform

this study.

7.2. Author contribution

All the authors met the 4 criteria recommended by the in-

ternational committee of medical journal editors for gaining

authorship.

7.3. Funding/Support

None.

7.4. Conflict of interest

All authors declare that they have no conflict of interest.

References

1. Pecoraro RE, Reiber GE, Burgess EM. Pathways to dia-

betic limb amputation: basis for prevention. Diabetes

care. 1990;13(5):513-21.

2. Michail M, Jude E, Liaskos C, Karamagiolis S, Makrilakis

K, Dimitroulis D, et al. The performance of serum in-

flammatory markers for the diagnosis and follow-up of

patients with osteomyelitis. The international journal of

lower extremity wounds. 2013;12(2):94-9.

3. Abegunde DO, Mathers CD, Adam T, Ortegon M, Strong

K. The burden and costs of chronic diseases in low-

income and middle-income countries. The Lancet.

2007;370(9603):1929-38.

4. Lipsky BA, Moran GJ, Napolitano LM, Vo L, Nicholson S,

Kim M. A prospective, multicenter, observational study

of complicated skin and soft tissue infections in hospital-

ized patients: clinical characteristics, medical treatment,

and outcomes. BMC infectious diseases. 2012;12(1):227.

5. Lipsky BA. A report from the international consensus on

diagnosing and treating the infected diabetic foot. Dia-

betes/metabolism research and reviews. 2004;20(S1).

6. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ,

Armstrong DG, et al. 2012 Infectious Diseases Society of

America Clinical Practice Guideline for the Diagnosis and

Treatment of Diabetic Foot Infections a. Clinical infec-

tious diseases. 2012;54(12):e132-e73.

7. Wrobel JS, Connolly J. Making the diagnosis of os-

teomyelitis. The role of prevalence. Journal of the Ameri-

can Podiatric Medical Association. 1998;88(7):337-43.

8. Grayson ML, Gibbons GW, Balogh K, Levin E, Karchmer

AW. Probing to bone in infected pedal ulcers: a clini-

cal sign of underlying osteomyelitis in diabetic patients.

Jama. 1995;273(9):721-3.

9. Leichter SB, Allweiss P, Harley J, Clay J, Kuperstein-

Chase J, Sweeney GJ, et al. Clinical characteristics of dia-

betic patients with serious pedal infections. Metabolism.

1988;37(2):22-4.

10. Armstrong DG, Lavery LA, Sariaya M, Ashry H. Leuko-

cytosis is a poor indicator of acute osteomyelitis of the

foot in diabetes mellitus. The Journal of foot and ankle

surgery. 1996;35(4):280-3.

11. Association AD. Diagnosis and classification of diabetes

mellitus. Diabetes care. 2014;37(Supplement 1):S81-S90.

12. Asten SA, Jupiter DC, Mithani M, La Fontaine J, Davis KE,

Lavery LA. Erythrocyte sedimentation rate and CâĂŘre-

This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).
Downloaded from: http://journals.sbmu.ac.ir/aaem



5 Archives of Academic Emergency Medicine. 2020; 8(1): e71

active protein to monitor treatment outcomes in dia-

betic foot osteomyelitis. International wound journal.

2017;14(1):142-8.

13. Lavery LA, Peters EJ, Armstrong DG, Wendel CS, Mur-

doch DP, Lipsky BA. Risk factors for developing os-

teomyelitis in patients with diabetic foot wounds. Dia-

betes research and clinical practice. 2009;83(3):347-52.

14. Lipsky BA, Itani K, Norden C, Group LDFIS. Treating

foot infections in diabetic patients: a randomized, mul-

ticenter, open-label trial of linezolid versus ampicillin-

sulbactam/amoxicillin-clavulanate. Clinical Infectious

Diseases. 2004;38(1):17-24.

15. Kaleta JL, Fleischli JW, Reilly CH. The diagnosis of os-

teomyelitis in diabetes using erythrocyte sedimentation

rate: a pilot study. Journal of the american podiatric med-

ical association. 2001;91(9):445-50.

16. Carragee EJ, Kim D, van der Vlugt T, Vittum D. The clinical

use of erythrocyte sedimentation rate in pyogenic verte-

bral osteomyelitis. Spine. 1997;22(18):2089-93.

17. Jones N, Anderson D, Stiles P. Osteomyelitis in a general

hospital. A five-year study showing an increase in suba-

cute osteomyelitis. Bone & Joint Journal. 1987;69(5):779-

83.

18. Lewis VL, Bailey MH, Pulawski G, Kind G, Bashioum RW,

Hendrix RW. The diagnosis of osteomyelitis in patients

with pressure sores. Plastic and reconstructive surgery.

1988;81(2):229-32.

19. YapÄścÄś O, Berk H, ÃŰztoprak N, Seyman D, Tah-

maz A, Merdin A. Can ratio of neutrophil-to-lymphocyte

count and erythrocyte sedimentation rate in diabetic

foot infecti on predict osteomyelitis and/or amputation?

Hematology reports. 2017;9(1).

This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).
Downloaded from: http://journals.sbmu.ac.ir/aaem


	Introduction
	Methods
	Results
	Discussion
	Limitations
	Conclusion
	Declarations
	References