Serum Procalcitonin is a sensitive and specific marker in the diagnosis of septic arthritis and acute osteomyelitis
© Karthikeyan et al.; licensee BioMed Central Ltd. 2013
Received: 3 December 2011
Accepted: 28 June 2013
Published: 4 July 2013
Early diagnosis of Acute Osteomyelitis (OM) and Septic Arthritis (SA) is of vital importance to avoid devastating complications. There is no single laboratory marker which is sensitive and specific in diagnosing these infections accurately. Total Count, ESR and CRP are not specific as they can also be elevated in non pyogenic causes of inflammation. Pus Culture and sensitivity is not a true gold standard due to its varied positivity rates (40 – 70%). Serum Procalcitonin (PCT), at 0.5 ng/ml is found to be an accurate marker for pyogenic infections. The objectives of this study were to show that PCT is an accurate marker in differentiating Acute Osteomyelitis and Septic Arthritis from viral and non infective inflammatory bone and joint conditions.
Patients of all age groups (n = 82) with suspected Acute Osteomyelitis and Septic Arthritis were prospectively included in this study. All patients were subjected to TC, CRP, PCT, IgM Dengue, IgM Chikungunya, pus and blood culture and sensitivity. At the end of the study, patients were classified into 3 groups: Group 1 = Confirmed Pyogenic (n = 27); Group 2 = Presumed Pyogenic (n = 21); Group 3 = Non – infective inflammatory (n = 34).
Group 1 has higher mean PCT levels than Group 2 and 3 (p < 0.05). PCT, at 0.4 ng/ml, was 85.2% sensitive and 87.3% specific in diagnosing Septic Arthritis and Acute Osteomyelitis. In comparison, PCT at conventional cut – off of 0.5 ng/ml is 66.7% sensitive and 91% specific.
Serum Procalcitonin, at a cut – off of 0.4 ng/ml, is a sensitive and specific marker in the diagnosis of Septic Arthritis and Acute Osteomyelitis.
KeywordsSerum Procalcitonin Septic Arthritis Acute Osteomyelitis Diagnosis Inflammatory Marker
Acute bone and joint infections are truly a diagnostic enigma in the Emergency Department. Management of these focuses on providing a rapid etiologic diagnosis since therapies and outcome vary widely depending upon the cause. Delayed diagnosis and treatment leading to disabling sequelae are not uncommon. Functional disabilities occur in 25 to 50% of cases and can even be life threatening in 5 to 15% of cases [1–3]. Total Count (TC), Erythrocyte Sedimentation Rate (ESR) and C – Reactive Protein (CRP) are routinely used in the diagnosis of these infections but no specific laboratory test exists with the exception of isolation of pathogenic organism from the bone or synovial fluid [4, 5]. A positive culture result has high specificity but even this cannot be considered as gold standard because it lacks sensitivity (only 40-60%) and the results are available only after 2 to 3 days [2, 3]. Despite this fact, culture is being used by many researchers as positive gold standard and patients without any clinical evidence plus negative culture as negative gold standard. The lack of sensitive laboratory markers or a gold standard investigation for diagnosing bacterial infections clinically has contributed to the overuse of antibiotics especially in neonates and elderly patients where clinical signs could be very subtle. The concept of providing antibiotics for every suspected infection is slowly being withdrawn because of emerging issues with antimicrobial resistance.
In this regard, there is a need for a biochemical marker which shows high sensitivity and specificity in diagnosing infection and also as a guide for starting antibiotics. There is now enough evidence to support the role of Procalcitonin (PCT) as a diagnostic and prognostic marker in infective conditions with its very high specificity for bacterial infections [6–9]. On the contrary, there are only very few studies evaluating its efficacy in Septic Arthritis (SA) and Acute Osteomyelitis (OM) with varying results [10–14]. Serum levels of Procalcitonin is very low in healthy individuals (< 0.1 ng/ml) and increases rapidly in response to bacterial endotoxin [15, 16]. These properties together with a half life of 22 to 29 hours have made Procalcitonin, a convenient tool to monitor serious infections and to discriminate bacterial infections from viral and non infective inflammatory conditions [17, 18]. Owing to its high specificity, Procalcitonin can also be used as a guide for starting antibiotics and monitoring treatment [19, 20].
Hence this study was conducted prospectively with the objectives to show that PCT is an accurate marker in the diagnosis of Acute Osteomyelitis and Septic Arthritis. Early treatment can be started which can decrease the incidence of disabling sequelae.
Materials and methods
This study was conducted in the Department of Orthopaedics, in a 1200 bedded tertiary health – care centre from January 2010 to June 2011. We included all cases of suspected acute (less than 2 weeks) synovitis / arthritis and osteomyelitis of all age groups with no evidence of infection elsewhere. We excluded (1) all cases of chronic arthritis and chronic osteomyelitis; (2) cases where antibiotics were given before presenting to us. (3) cases with foci of infection elsewhere. (4) immunocompromised hosts. The study was approved by Institute Research council and Ethics Committee and conducted in accordance to the standards of Declaration of Helsinki, 1964. Detailed informed consent was obtained from all patients or from parents and legal guardians included in this study.
All patients were assessed for clinical parameters which included presence of swelling; joint effusion; tenderness; local warmth; deformity; range of movement restriction and presence of septicemic symptoms. Detailed proforma was used to record patient details and clinical findings. Plain radiography [Anteroposterior and Lateral views] and Ultrasound (USG) of the involved bone and joint were done. Under adequate anesthesia and proper aseptic precautions, Aspiration was done using 18G needle from the joint and bone with subperiosteal abscess. In the absence of subperiosteal abscess, aspirate was obtained by drilling the bone with 2 mm drill bit under anesthesia. This was followed by definitive surgery in the form of arthrotomy or incision and drainage (I&D).
Aspirate was immediately processed for the presence of pus cells, gram staining, culture and sensitivity (C/S). All patients were subjected to Blood C/S. Culture and sensitivity was considered as the gold standard in this study. Laboratory analyses included estimation of ESR, TC, CRP, Procalcitonin, IgM Dengue and IgM Chikungunya. ESR was estimated using Wintrobe’s method. CRP was measured using Nephelometer [BNPROSPEC, Germany]. The cut-off in our laboratory was 3.02 mg/l above which CRP was considered positive. PCT was determined by Quantitative Immunoluminetric test [LUMItest, BRAHMS Diagnostica, Berlin, Germany) by the investigator who followed the assay manufacturer’s recommendations. The threshold for PCT detection defined by our laboratory is 0.1 ng/ml. Samples were analyzed for IgM Dengue and IgM Chikungunya using ELISA technique. Dengue and Chikungunya are the commonest viral infections presenting with bone and joint symptoms in our region and the only feasible tests available in our institution. They were performed to rule out viral etiology for acute bone and joint infective conditions.
Patient Characteristics n = 82
Symptom duration (days)*
Males / Females
58 / 24
Age (years) ¥
25.33 (10 days – 86 years)
Confirmed pyogenic (C+SA / C+OM)
27 (19 / 8)
Presumed pyogenic (C-SA / C-OM)
21 (17 / 4)
Non – infective inflammatory
Transient synovitis of hip
Sickle cell crisis
Non – specific synovitisф
Blood C / S
Pus C / S (C+SA / C+OM)
27 (19 / 8)
Methicillin Resistant SA
20 (12 / 8)
3 (3 / 0)
Coagulase negative SA
1 (1 / 0)
1 (1 / 0)
1 (1 / 0)
1 (1 / 0)
Mean levels of TC, ESR, CRP and PCT were compared between these groups and sensitivity, specificity and predictive values of PCT were assessed.
The statistical significance of all parameters (TC, ESR, CRP and PCT) were analyzed using Independent Students T test and One Way ANOVA with BonFerroni PostHoc test. The sensitivity, specificity and predictive values were analyzed using SPSS software version 19. Newcombe method was used to calculate 95% confidence intervals (CI). p < 0.05 was considered statistically significant.
A total of 106 patients presented with clinical presentations suggestive of OM and SA. Out of these, 24 patients were excluded from the study as 11 patients gave a history of antibiotic administration before presentation and 13 patients had other foci of infection. The study group included 82 patients of all age groups (Table 1). The youngest was a 10 days old neonate and the oldest was 86 years of age with the mean age of 25.33 years. 23 patients (28.04%) were less than 5 years of age and 28 patients (34.14%) were above 40 years. Out of 82 patients, there were 58 males (70.73%) and 24 females (29.26). Blood culture was positive (11.11%) for MRSA in three cases, two cases of SA involving Hip joint and one case of OM of Distal Femur. MRSA was the commonest organism isolated from pus. It was positive in 74.07% of patients in Group 1; 63.16% in Group 1a and 100% in Group 1b. Viral analysis for IgM Dengue and Chikungunya did not yield any positive results.
Mean with SD for all parameters
P – value
On analysis of other parameters, the mean TC and ESR were found to have raised in Group 1 and 2 with statistical significance (p < 0.05). In contrast, Group 1 had higher CRP levels than Group 2 which is not statistically significant (p = 0.1).
Sensitivity and Specificity of PCT at various cut - offs
Confirmed / presumed Vs non infective
Confirmed Vs presumed / infective
Sensitivity, Specificity and Predictive values of PCT at 0.5 and 0.4 ng/ml
Sensitivity % 95% CI
Specificity % 95% CI
PPV % 95% CI
NPV % 95% CI
Confirmed Pyogenic vs presumed + Non – pyogenic
66.7 (46 – 83.4)
91 (80 – 97)
78.2 (56 – 92.5
85.2 (66.3 – 95.8)
87.3 (75.5 – 94.7)
76.6 (57.7 –90.1)
92.3 (81.5 - 98)
Confirmed+ Presumed vs non – pyogenic
47.9 (33.2 – 62.8)
100 (89.7 – 100)
100 (85.2 -100)
57.6 (44.1 -70.4)
62.5 (47.4 – 76)
100 (89.7 – 100)
100 (88.4 – 100)
65.4 (60 – 78)
Confirmed vs non – pyogenic
66.67 (46 – 83.4)
100 (91.2 - 100)
100 (87.4 – 100)
86.3 (77.8 – 94.9)
85.19 (66.3 – 95.8)
100 (90.2 – 100)
100 (88.7 – 100)
93.8 (82.7 - 96.5)
Septic Arthritis and Acute Osteomyelitis are relatively common entities in day to day orthopedic practice and in a tertiary referral centre like ours, it is more common. But the diagnosis of these infections faces the following problems: inadvertent use of antibiotics by the physician who first sees the patient before the proper diagnosis is made; pus culture and sensitivity which is often considered the gold standard is not a useful gold standard because of its low positivity rates; absence of a single laboratory parameter with high specificity and sensitivity; dubious presentations of these infections in the very young and the old; hence the search for a realistic laboratory marker is essential.
Many of the complications secondary to delayed diagnosis have come down in number due to the availability of powerful antibiotics but on the other hand this has led to the emergence of anti- microbial resistance due to its inadvertent and irrational use. This is of serious concern because practically only few drugs are available as of now to tackle serious infections [21–23]. PCT has been found to be a promising marker in diagnosing bacterial infections with its high specificity. Its usefulness over markers like TC, ESR and CRP has been described in several conditions like sepsis, upper respiratory tract infections, pneumonias, pancreatitis, pyelonephritis, burns and in various other conditions [18, 24, 25]. With this background, this study was conducted with the following objectives: To show that PCT is an accurate marker for differentiating OM and SA from viral infections and non infective inflammatory bone and joint conditions and to evaluate Sensitivity, Specificity and Predictive values of Serum Procalcitonin in diagnosing OM and SA.
Pus culture is expected to be positive in 40 to 60% in patients of SA and OM though it is 100% specific [2, 3]. In the present study, pus culture positivity is 56.25%. Staphylococcus aureus was described as the most common identifiable causative organism which accounts for more than 50% of isolated organism in acute hematogenous osteomyelitis and 30% in septic arthritis. MRSA is the commonest organism in the present study isolated in 74.07% of cases (63.16% of septic arthritis cases and 100% of acute osteomyelitis). Serum PCT level less than 0.5 ng/ml is considered normal [15, 17]. However, there is no unanimous agreement in deciding the cut – off because PCT is an emerging diagnostic marker and is either undetectable or very low in healthy individuals. Studies by Butbul Aviel et al., ; Fottner et al., ; Martinot et al.,  and Faesh et al.,  have taken 0.5 ng/ml as cut – off above which it is considered as a marker of pyogenic infection. However, study by Hogle et al.,  has taken 0.25 ng/ml as the cut-off. This reflects the absence of a general consensus in deciding the cut-off.
There are only few studies evaluating the efficacy of PCT in SA and OM. Butbul Aviel et al.,  in 2005, have shown that PCT at 0.5 ng/ml was a poorly sensitive but highly specific marker using a semi quantitative PCT card test with higher sensitivity for OM than SA. However, we have not attempted to analyze separately for SA and OM as PCT as a marker can diagnose only the presence and severity of infection and is not influenced by the site of infection. Similarly, studies by Fottner et al., ; Martinot et al.,  and Sabine Faesch et al.,  have shown PCT as a poorly sensitive marker with high specificity at a cut-off of 0.5 ng/ml. This could be due to the low sample size as reflected in all these studies. The study by Hogle et al.,  has shown PCT as a highly sensitive marker but low specific marker at a cut-off of 0.25 ng/ml. The present study has included 36 patients of SA and 12 patients of OM which is considerably higher when compared to other studies. The present study has shown equally high sensitivity and specificity when compared to other groups. The strengths of the present study are: Prospective study; the number of patients with septic arthritis and acute osteomyelitis are more when compared to other studies; this study has included patients of all age groups; the LUMItest [BRAHMS Diagnostica] used has a very low detection limit of 0.1 ng/ml. The limitation of our study is that overall sample size is low but not to extent of affecting statistical analysis. We have included patients all age groups (10 days old to 86 years). Though this might have an impact on sensitivity and specificity rates, majority of patients (66%) in our study were less than 40 years. Through this study, we would also like to show that adult septic arthritis is not an uncommon entity, atleast in our parts of the world. Ours is a tertiary referral hospital catering to different referral patterns. Though this might have an impact on the result of this study, it is less likely as we stringently followed our inclusion criteria. We have included only cases of dengue and chikungunya as these are the only relevant viral infections common in our region but these may not be common in other parts of the world. The present study was designed to assess the diagnostic value of PCT. Hence serial PCT measurements which will help us to study its prognostic significance were not done.
The present study has shown that Serum Procalcitonin, at a cut – off of 0.4 ng/ml, is a sensitive and specific marker in the diagnosis of Acute Osteomyelitis and Septic Arthritis. This is in comparison to the conventional cut – off of 0.5 ng/ml which is specific but less sensitive. Thus, Serum Procalcitonin may be used as a new diagnostic marker for initiation of treatment in the management of Acute Osteomyelitis and Septic arthritis.
Erythrocyte sedimentation rate
C – reactive protein
We would like to acknowledge the efforts of Dr.Harichandrakumar, consultant biostatistician for helping us in the statistical analysis of data.
- Georgens ED, McEvoy A, Watson M, Barrett IR: Acute osteomyelitis and septic arthritis in children. J Paediatr Child Health. 2005, 41: 59-62. 10.1111/j.1440-1754.2005.00538.x.View ArticleGoogle Scholar
- Morrey BF, Bianco AJ, Rhodes KH: Septic arthritis in children. Orthop Clin North Am. 1975, 6 (4): 923-934.PubMedGoogle Scholar
- Mathews CJ, Weston VC, Jones A, Field M, Coakley G: Bacterial septic arthritis in adults. Lancet. 2010, 375: 846-855. 10.1016/S0140-6736(09)61595-6.View ArticlePubMedGoogle Scholar
- Unkila-Kallio L, Kallio MJ, Eskola J, Peltola H: Serum C – reactive protein, erythrocyte sedimentation rate, and white blood cell count in hematogenous osteomyelitis of children. Pediatrics. 1994, 93: 59-62.PubMedGoogle Scholar
- Levine MJ, McGuire KJ, McGowan KL, Flynn JM: Assessment of the test characteristics of C – reactive protein for septic arthritis in children. J Pediatr Orthop. 2003, 23: 373-377.PubMedGoogle Scholar
- Crain M, Muller B: Procalcitonin in bacterial infections– hype, hope, more or less?. Swiss Med Wkly. 2005, 135: 451-460.Google Scholar
- Gendrel D, Bohoun C: Procalcitonin in pediatrics for differentiation for bacterial and viral infections. Intensive Care Med. 2000, 26: 178-181.View ArticleGoogle Scholar
- Ghorbani G: Procalcitonin role in differential diagnosis of infection stages and non infection inflammation. Pak J Biol Sci. 2009, 15 (12(4)): 393-396.View ArticleGoogle Scholar
- Chan YL, Tseng CP, Tsay PK, Chang SS, Chiu TF: Procalcitonin as a marker of bacterial infection in the emergency department: an observational study. Critical Care. 2004, 8: 1-10.1186/cc2404.View ArticleGoogle Scholar
- Butbul Y, Koren A, Halevy R, Sakran W: Procalcitonin as a diagnostic aid in osteomyelitis and septic arthritis. Pediatric Emer Care. 2005, 21 (12): 828-832. 10.1097/01.pec.0000190226.12610.24.View ArticleGoogle Scholar
- Fottner A, Birkenmaier C, von Schulze PC, Wegener B, Jansson V: Can serum procalcitonin help to differentiate between septic and nonseptic arthritis?. Arthroscopy. 2008, 24 (2): 229-233. 10.1016/j.arthro.2007.07.029.View ArticlePubMedGoogle Scholar
- Hügle T, Schuetz P, Mueller B, Laifer G, Tyndall A, Regenass S, Daikeler T: Serum procalcitonin for discrimination between septic and non-septic arthritis. Clin Exp Rheumatol. 2008, 26 (3): 453-456.PubMedGoogle Scholar
- Martinot M, Sordet C, Soubrier M, Puéchal X, Saraux A, Lioté F: Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients. Clin Exp Rheumatol. 2005, 23 (3): 30310-Google Scholar
- Faesch S, Cojocaru B, Hennequin C, Pannier S, Glorion C: Can procalcitonin measurement help the diagnosis of osteomyelitis and septic arthritis? a prospective trial. Italian Journal of Pediatrics. 2009, 35: 33-10.1186/1824-7288-35-33.PubMed CentralView ArticlePubMedGoogle Scholar
- Barresi A, Pallotti F, d'Eril GVM: Biological variation of procalcitonin in healthy individuals. Clin Chem. 2004, 50: 1878-View ArticleGoogle Scholar
- Assicot M, Mackensen A, Petitjean S, Engelhardt R, Bohuon C: Kinetics of the appearance of procalcitonin following endotoxin administration. Lancet. 1993, 27 (341(8844)): 515-518.View ArticleGoogle Scholar
- Shimetani N, Ohba Y, Shimetani K, Mashiko T, Matsuyama N, Ohtani H, Morii M: Assay for determination of the serum procalcitonin level: biochemical and clinical evaluation. Rinsho Byori. 2001, 49 (1): 56-60.PubMedGoogle Scholar
- Delevaux I, André M, Colombier M, Albuisson E, Meylheuc F, Bègue RJ: Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes?. Ann Rheum Dis. 2003, 62 (4): 337-340. 10.1136/ard.62.4.337.PubMed CentralView ArticlePubMedGoogle Scholar
- Oh JS, Kim SU, Oh YM, Choe SM, Choe GH: The usefulness of the semi quantitative procalcitonin test kit as a guideline for starting antibiotic administration. Am J Emerg Med. 2009, 27 (7): 859-863. 10.1016/j.ajem.2008.06.021.View ArticlePubMedGoogle Scholar
- Holub M, Rozsypal H, Chalupa P: Procalcitonin: a reliable marker for the diagnosis and monitoring of the course of bacterial infection. Klin Mikrobiol Infekc Lek. 2008, 14 (6): 201-208.PubMedGoogle Scholar
- Simon L, Gauvin F, Amrre DK, Louis PS, Lacroix J: Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2005, 40 (9): 1386-1388.View ArticleGoogle Scholar
- Kite P, Millar MR, Gorham P, Congdon P: Comparison of five tests used in diagnosis of neonatal bacteraemia. Arch Dis Child. 1988, 63 (6): 639-643. 10.1136/adc.63.6.639.PubMed CentralView ArticlePubMedGoogle Scholar
- Hatherill M, Tibby SM, Sykes K, Turner C, Murdoch IA: Diagnostic markers of infection: comparison of procalcitonin with C - reactive protein and leukocyte count. Arch Dis Child. 1999, 81 (5): 417-421. 10.1136/adc.81.5.417.PubMed CentralView ArticlePubMedGoogle Scholar
- Eberhard K, Haubitz M, Brunkhorst M, Kliem V, Koch M: Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease and invasive bacterial infection. Arthritis and Rheumatism. 1997, 40: 7-View ArticleGoogle Scholar
- Becker KL, Snider R, Nylen ES: Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008, 36: 3-10.1097/01.CCM.0000296264.41365.80.View ArticleGoogle Scholar
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