Abstract
Aims
Three-phase bone scintigraphy (TPBS) is a simple, reliable, and straightforward imaging modality for diagnosing periprosthetic joint infection (PJI). This study aimed to evaluate the diagnostic efficacy of the combined diagnostic method of TPBS and CRP in the detection of PJI.
Methods
A retrospective analysis was performed on 317 patients undergoing revision surgery (211 hips and 106 knees) between January 2017 and January 2024, with TPBS obtained prior to surgical intervention. PJI was diagnosed according to the 2013 Musculoskeletal Infection Society (MSIS) criteria. The diagnostic performance of TPBS, CRP, and TPBS-CRP combined method was evaluated.
Results
In the total knee arthroplasty (TKA) cohort, TPBS-CRP achieved maximal sensitivity (100%) and negative predictive value (100%), enabling definitive exclusion of PJI, albeit with reduced specificity (50.0%). Antibiotic therapy significantly reduced CRP accuracy (79.1% vs 97.1%, p = 0.020) but minimally impacted TPBS (100% vs 88.6%, p = 0.037). For total hip arthroplasty (THA), the TPBS-CRP demonstrated a superior diagnostic efficacy (AUC = 0.846, 0.834, and 0.795) and demonstrated a more balanced sensitivity (81.6%, 67.3%, and 64.3%) and specificity (87.6%, 91.2%, and 94.7%) compared to CRP and TPBS. Antibiotic-treated patients exhibited significantly higher diagnostic accuracy for TPBS (81.5% vs 57.7%, p = 0.028), CRP (88.9% vs 59.2%, p = 0.005), and TPBS-CRP (96.3% vs 76.1%, p = 0.020) compared to untreated patients. False-positive TPBS cases in both cohorts exhibited severe bone loss and prolonged symptoms compared to true negatives (p < 0.05).
Conclusion
TPBS demonstrates limited specificity in differentiating PJI from aseptic loosening. The TPBS-CRP synergizes localized bone metabolic profiles with systemic inflammatory biomarkers, achieving superior diagnostic accuracy. Caution is warranted in patients with severe bone loss and prolonged symptoms.
Cite this article: Bone Joint Res 2026;15(4):354–362.
Keywords: Three-phase bone scintigraphy, Periprosthetic joint infection, CRP, Antibiotic, bone scintigraphy, Periprosthetic joint infection (PJI), total knee arthroplasty (TKA), total hip/knee arthroplasties, antibiotics, aseptic loosening, bone loss, knees, hips
Article focus
To evaluate the diagnostic efficacy of three-phase bone scintigraphy (TPBS) for periprosthetic joint infection (PJI).
To evaluate the diagnostic efficacy of TPBS combined with CRP in the detection of PJI.
Key messages
TPBS demonstrates limited specificity in distinguishing PJI from aseptic loosening and cannot serve as a standalone diagnostic tool for PJI.
The TPBS-CRP diagnostic method integrates localized bone metabolic characteristics with systemic inflammatory biomarkers, demonstrating superior diagnostic accuracy.
Strengths and limitations
Our study establishes a dual-modality evaluation framework that synchronizes localized osseous metabolic activity with systemic inflammatory indices, demonstrating enhanced diagnostic precision for PJI.
Our study had a small sample size and was a single-centre study, which may have introduced bias. Therefore, future research should aim to increase the sample size and conduct multicentre studies to validate these findings.
Introduction
Periprosthetic joint infection (PJI), occurring in 1% to 2% of total hip/knee arthroplasties (THAs/TKAs), represents a catastrophic complication associated with elevated mortality rates, prolonged hospitalization, and substantial healthcare burdens.1-3 Early and accurate diagnosis is critical for effective management; however, PJI diagnosis remains clinically challenging due to non-specific early symptoms and the absence of a gold-standard test, particularly in differentiating PJI from aseptic loosening.
In recent years, nuclear imaging techniques have emerged as valuable tools for diagnosing PJI. These methods sensitively detect active bone metabolism and localize infection/loosening sites by visualizing radiotracer uptake patterns.4,5 Among them, three-phase bone scintigraphy (TPBS) demonstrates distinct advantages over fluorodeoxyglucose-positron emission tomography (FDG-PET) and leucocyte scintigraphy, including higher sensitivity, operational simplicity, and cost-effectiveness, making it more suitable as a screening tool.5-8 However, TPBS suffers from limited specificity due to non-specific uptake in noninfectious bone remodelling and poor detection of low-virulence infections.8,9 Complementarily, CRP, a systemic inflammatory marker, exhibits high sensitivity and specificity in the diagnosis of PJI and is recommended in PJI diagnostic guidelines.10-15 Nevertheless, CRP alone remains insufficient for confirming chronic or low-grade infections, as suppressed systemic inflammation may yield false-negative results.
To address these limitations, this study combined TPBS with CRP for diagnosing PJI. We hypothesized that, by integrating localized bone metabolic signatures (TPBS) with systemic inflammatory biomarkers (CRP), it can not only achieve ideal sensitivity and specificity but also help reduce the misdiagnosis rate and improve the accuracy of clinical decision-making. We aimed to explore the combined application value of TPBS and CRP in the diagnosis of PJI and to provide evidence for the early diagnosis of PJI.
Methods
Study population
This study enrolled 321 patients who underwent revision surgery at our institution between January 2017 and January 2024 and had undergone TPBS preoperatively. Patients were excluded for insufficient clinical data, inflammatory rheumatic or autoimmune diseases, malignancy history, or prosthesis-related pain (dislocation/periprosthetic fracture). Figure 1 shows a flowchart of the work. A total of 317 patients (211 THAs and 106 TKAs) were available for analysis, including 134 men and 183 women, with a mean age of 61.2 years (24 to 92), after excluding four patients due to insufficient imaging data. The characteristics of 317 joints are listed in Table I.
Fig. 1.
Flowchart showing the constitution of the cohort. THA, total hip arthroplasty; TKA, total knee arthroplasty; TPBS, three-phase bone scintigraphy.
Table I.
Characteristics of the patients included in this study.
| Characteristic | THA | TKA |
|---|---|---|
| Number of patients | 211 | 106 |
| Mean age, yrs (range) | 58.4 (24 to 84) | 67.3 (28 to 92) |
| Sex, n (%) | ||
| Female | 106 (50.24) | 28 (26.42) |
| Male | 105 (49.76) | 78 (73.58) |
| Mean time interval from implantation to bone scanning, mths (range) | 106.0 (3 to 372) | 60.0 (3 to 270) |
| Mean duration of symptoms, mths (range) | 15.6 (0.03 to 156) | 12.6 (0.1 to 132) |
| MSIS, n (%) | ||
| Infection | 98 (46.4) | 78 (73.6) |
| Aseptic loosening | 113 (53.6) | 28 (26.4) |
| TPBS, n (%) | ||
| Infection | 69 (32.70) | 87 (82.1) |
| Aseptic loosening | 142 (67.30) | 19 (17.9) |
| CRP, n (%) | ||
| Infection | 76 (36.0) | 71 (67) |
| Aseptic loosening | 135 (64.0) | 35 (33) |
| TPBS-CRP, n (%) | ||
| Infection | 94 (44.5) | 92 (86.8) |
| Aseptic loosening | 117 (55.5) | 14 (13.2) |
MSIS, Musculoskeletal Infection Society; THA, total hip arthroplasty; TKA, total knee arthroplasty; TPBS, three-phase bone scintigraphy.
Definition of bone defects
The Anderson Orthopaedic Research Institute (AORI) Classification was applied to evaluate post-TKA bone defects, with Type I denoting mild bone loss, Type II moderate bone loss, and Type III severe bone loss.16 The Paprosky classification was employed to assess acetabular and femoral bone defects following THA.17,18 For acetabular defects: Type I designates mild bone loss, Type II moderate, and Type III severe. Femoral defects classify Type I as mild, Type II as moderate, with Types III and IV constituting severe bone loss. The final grading was determined by the most severe defect present in either anatomical site.
Acquisition protocol of 99mTcMDP TPBS
TPBS procedure adhered to the practice guidelines for bone scintigraphy established by the European Association of Nuclear Medicine.19 TPBS utilizing 99mTc-methylene diphosphonate was performed on a dual-detector single-photon emission CT system (Siemens Symbia Evo Excel; Siemens, Germany) configured with low-energy, high-resolution collimators, and a dual-head gamma camera. All patients received a commercial injection of 740 MBq of 99m Tc-MDP. The perfusion stage (immediately after injection; 3 s/frame, 40 frames) was used to obtain the blood flow phase, the soft-tissue phase (5 mins after injection; 60 s/frame, 5 frames) was used to obtain the blood pool phase, and the delay phase was obtained in the delayed metabolism stage (3 hrs after tracer injection, 1 frame).
Image interpretation and diagnostic classification
The 99mTc-MDP TPBS images were jointly analyzed by two senior nuclear medicine physicians (ADL, WM). In cases of disagreement, a third experienced physician (YB) made the final determination. The evaluation criteria for TPBS were based on the pattern and location of 99mTcMDP uptake. A normal manifestation is mild tracer accumulation or no uptake at the bone-prosthesis interface; for patients with prosthesis loosening, there is no abnormal tracer accumulation in the blood flow phase and blood pool phase, but focal/linear/patchy abnormal uptake around the prosthesis appears in the delayed phase; PJI is manifested as abnormal uptake around the prosthesis in the blood flow phase and blood pool phase, and diffuse accumulation is observed in the delayed phase (Figure 2 and Figure 3). Serum CRP levels were quantified using an automated immunoturbidimetric assay (Beckman Coulter, USA). A threshold of > 10 mg/L was defined as diagnostic of PJI, while values ≤ 10 mg/L indicated aseptic loosening. In the combined diagnostic method integrating TPBS and CRP, positive criteria were defined as either TPBS findings consistent with PJI or CRP levels > 10 mg/L. Negative criteria required TPBS evidence of aseptic loosening/normal prosthesis and CRP ≤ 10 mg/L. PJI diagnosis necessitated positivity in either TPBS or CRP, while aseptic loosening was confirmed only when both TPBS and CRP results were negative.
Fig. 2.
Three-phase bone scintigraphy (TPBS) of patients with infection and aseptic loosening after total hip arthroplasty. In patients with hip infection (A, B, and C representing the blood flow phase, blood pool phase, and delayed phase respectively), increased 99mTc-methylene diphosphonate (99mTc-MDP) uptake is observed in the proximal left thigh across all three phases (arrow). In a patient with aseptic loosening (D, E, and F representing the blood flow phase, blood pool phase, and delayed phase), no increased 99mTc-MDP uptake is observed in the blood flow and blood pool phases. However, increased 99mTc-MDP uptake is seen in the mid-to-upper segment of the left femur during the delayed phase (arrow).
Fig. 3.
Three-phase bone scintigraphy (TPBS) of patients with infection and aseptic loosening after total knee arthroplasty. In patients with knee infection (A, B, and C representing the blood flow phase, blood pool phase, and delayed phase respectively), increased 99mTc-methylene diphosphonate (99mTc-MDP) uptake is observed in the right knee across all three phases (arrow). In a patient with aseptic loosening (D, E, and F representing the blood flow phase, blood pool phase, and delayed phase), no increased 99mTc-MDP uptake is observed in the blood flow and blood pool phases. However, increased 99mTc-MDP uptake is seen in the medial condyle of the right tibia during the delayed phase (arrow).
The final diagnostic criteria define PJI according to the modified Musculoskeletal Infection Society criteria,13 while implant failure which did not fulfil these criteria was classified as aseptic failure.
Statistical analysis
Data were reported as mean and SD or median and IQR. Between-group comparisons were conducted using independent samples t-tests for continuous variables, and chi-squared tests or Fisher’s exact tests (when expected cell counts fell below 5) for categorical variables. Chi-squared test was employed to calculate the true-positive rate (TPR), true-negative rate (TNR), false-positive rate (FPR), and false-negative rates (FNR). The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were then calculated. Receiver operating characteristic (ROC) curves were drawn to compare the diagnostic efficacy of TPBS, CRP, and TPBS-CRP with the area under the curve (AUC) used to evaluate this efficacy (p < 0.05). Statistical analyses were performed with SPSS Statistics (v25.0; IBM, USA).
Results
Study population
A total of 317 patients (211 hips and 106 knees) were available for analysis. Utilizing the MSIS criteria, PJI was confirmed in 176 patients (98 hips and 78 knees), whereas aseptic loosening accounted for the remaining 141 cases (113 hips and 28 knees). In the TKA group, the number of cases diagnosed as PJI by TPBS, CRP, and TPBS-CRP were 87, 71, and 92 respectively; in the THA group, the diagnoses by TPBS, CRP, and TPBS-CRP were 69, 76, and 94 respectively (Table I).
Sensitivity, specificity, and diagnostic efficacy
In the TKA cohort, TPBS demonstrated high sensitivity (94.9%) but limited specificity (53.6%) for PJI diagnosis, whereas CRP showed superior sensitivity and specificity (87.2% and 89.3%). The TPBS-CRP achieved maximal sensitivity (100%) and negative predictive value (100%) for PJI exclusion, albeit with reduced specificity (50.0%). Diagnostic accuracies for TPBS-CRP, CRP, and TPBS were 86.8%, 87.7%, and 84.0%, respectively. At the same time, the ROC curve shows the diagnostic effects of different methods for PJI, with AUC values of 0.889 and 0.742 for CRP and TPBS, respectively, while the AUC value for TPBS-CRP is only 0.750. These results indicate that although the method lacks sufficient diagnostic efficacy for confirming PJI, it is completely reliable for excluding infection (Table II, Figure 3).
Table II.
Diagnostic efficacy of three-phase bone scintigraphy (TPBS), CRP, and TPBS-CRP in total knee arthroplasty.
| Method | No. cases | Sensitivity, % | Specificity, % | Accuracy, % | NPV, % | AUC | |||
|---|---|---|---|---|---|---|---|---|---|
| TP | TN | FP | FN | ||||||
| TPBS | 74 | 15 | 13 | 4 | 94.9 | 53.6 | 84.0 | 79.0 | 0.742 (0.620 to 0.864) |
| CRP | 68 | 25 | 3 | 10 | 87.2 | 89.3 | 87.7 | 71.4 | 0.889 (0.815 to 0.964) |
| TPBS-CRP | 78 | 14 | 14 | 0 | 100 | 50 | 86.8 | 100 | 0.750 (0.626 to 0.874) |
AUC, area under the curve; FN, false-negative; FP, false-positive; NPV, negative predictive value; TN, true negative; TP, true positive.
Within the THA group, the sensitivity and specificity for diagnosing prosthetic hip infection using TPBS-CRP were 81.6% and 87.6%, respectively. The sensitivity was superior to that of TPBS (64.3%) and CRP (67.3%), but the specificity was inferior to that of TBS (94.7%) and CRP (91.2%). The AUC of the TPBS-CRP (0.846) surpassed both CRP (0.834) and TPBS (0.795), with superior diagnostic accuracy (84.8%, 80.1%, and 80.6%), indicating that the TPBS-CRP has a better combination of diagnostic capacity and validity (Table III, Figure 4).
Table III.
Diagnostic efficacy of three-phase bone scintigraphy (TPBS), CRP, and TPBS-CRP in total hip arthroplasty.
| Method | No. cases | Sensitivity, % | Specificity, % | Accuracy, % | NPV, % | AUC | |||
|---|---|---|---|---|---|---|---|---|---|
| TP | TN | FP | FN | ||||||
| TPBS | 63 | 107 | 6 | 35 | 64.3 | 94.7 | 80.6 | 75.4 | 0.795 (0.730 to 0.859) |
| CRP | 66 | 103 | 10 | 32 | 67.3 | 91.2 | 80.1 | 76.3 | 0.834 (0.776 to 0.892) |
| TPBS-CRP | 80 | 99 | 14 | 18 | 81.6 | 87.6 | 84.8 | 84.6 | 0.846 (0.789 to 0.903) |
AUC, area under the curve; FN, false-negative; FP, false-positive; NPV, negative predictive value; TN, true negative; TP, true positive.
Fig. 4.
The receiver operating characteristic curve for each culture method. AUC, area under the curve; THA, total hip arthroplasty; TKA, total knee arthroplasty; TPBS, three-phase bone scintigraphy.
Notably, false-positive TPBS cases in both TKA and THA cohorts exhibited significantly greater periprosthetic bone loss (p < 0.05) and prolonged symptom duration compared to true-negative cases (p < 0.05, Table IV).
Table IV.
Degree of bone defects and the duration of symptoms included in three-phase bone scintigraphy.
| Symptom | TN | FP | p-value |
|---|---|---|---|
| TKA, n | 15 | 13 | NI |
| Degree of bone defects, n | 0.042* | ||
| Mild bone loss | 6 | 0 | |
| Moderate bone loss | 7 | 10 | |
| Severe bone loss | 2 | 3 | |
| Mean duration of symptoms, mths (range) | 14.4 (0.1 to 60) | 46.1 (0.2 to 132) | 0.023† |
| Mean time interval from implantation to bone scanning, mths (range) | 116.5 (3 to 270) | 98.2 (3 to 179) | 0.539† |
| THA, n | 107 | 6 | NI |
| Degree of bone defects, n | 0.045* | ||
| Mild bone loss | 12 | 0 | |
| Moderate bone loss | 73 | 2 | |
| Severe bone loss | 22 | 4 | |
| Mean duration of symptoms, mths (range) | 16.1 (0.1 to 156) | 55.7 (1 to 72) | 0.001† |
| Mean time interval from implantation to bone scanning, mths (range) | 132.5 (3 to 372) | 156.7 (58 to 216) | 0.442† |
Fisher’s exact test.
Independent-samples t-test.
FN, false-negative; FP, false-positive; NI, not included; THA, total hip arthroplasty; TKA, total knee arthroplasty.
Effect of preoperative antimicrobial therapy on diagnostic efficacy
Among 78 patients with prosthetic knee infections, 43 (55.1%) received antimicrobial therapy within two weeks prior to evaluation. In antibiotic-treated patients, TPBS maintained high diagnostic accuracy (100%, 43/43), significantly outperforming the non-antibiotic group (88.6%, 31/35, p = 0.037). Conversely, CRP accuracy was substantially reduced with antibiotic therapy (79.1% vs 97.1%, p = 0.020). Notably, the combined TPBS-CRP achieved 100% diagnostic accuracy (78/78) regardless of antibiotic use.
In the hip cohort, 27 of 98 prosthetic hip infection cases (27.6%) received preoperative antibiotics. Antibiotic-treated patients exhibited significantly higher diagnostic accuracy for TPBS (81.5% vs 57.7%, p = 0.028), CRP (88.9% vs 59.2%, p = 0.005), and TPBS-CRP (96.3% vs 76.1%, p = 0.020) compared to untreated patients (Table V).
Table V.
Diagnostic accuracy in periprosthetic joint infection patients with versus without antibiotic therapy.
| Variable | TPBS, % | CRP, % | TPBS-CRP, % |
|---|---|---|---|
| THA | |||
| Antibiotic-treated group | 87.5 | 88.9 | 96.3 |
| Non-antibiotic group | 57.7 | 59.2 | 76.1 |
| TKA | |||
| Antibiotic-treated group | 100 | 79.1 | 100 |
| Non-antibiotic group | 88.6 | 97.1 | 100 |
THA, total hip arthroplasty; TKA, total knee arthroplasty; TPBS, three-phase bone scintigraphy.
Discussion
PJI represents a devastating complication following arthroplasty. Despite advancements in diagnostic methods, the absence of a gold-standard test persists as a critical challenge.20,21 While CRP serves as a pivotal inflammatory marker for PJI screening, its standalone application lacks sufficient specificity to confirm chronic or low-grade infections.10,22 Conversely, bone scintigraphy—unlike conventional imaging techniques (radiograph, CT, and MRI)—avoids implant-related artifacts and demonstrates superior diagnostic utility.5,23,24 Although single-photon emission CT/CT (SPECT/CT) enhances lesion localization and diagnostic specificity through CT-based anatomical imaging, and positron emission tomography/CT (PET/CT) offers exceptional anatomical detail and metabolic information with high sensitivity and specificity, their widespread application is limited by the requirement for advanced equipment and high costs.5-8 In contrast, TPBS provides functional insights into bone metabolism, and is regarded as a conventional screening tool due to its high sensitivity, cost-effectiveness, and procedural simplicity. However, growing evidence indicates its limitations in diagnosing PJI. Hill et al25,26 reported suboptimal TPBS performance in PJI diagnosis and suggested that it should not be used as the preferred diagnostic test. Our findings further validate these concerns, and across both TKA and THA cohorts, TPBS demonstrated the lowest diagnostic accuracy among all methods evaluated, indicating that relying solely on TPBS to diagnose PJI is clearly inappropriate. To overcome this clinical hurdle, the application of the TPBS-CRP in diagnosing PJI within the TKA cohort demonstrated that the method attained the highest level of sensitivity (100%) and NPV (100%). This characteristic allowed for the conclusive exclusion of PJI when both methods yielded negative results, even though the method exhibits a diminished specificity (50%). In the THA cohort, TPBS-CRP demonstrated ideal sensitivity (81.6%) and specificity (87.6%), with an AUC value superior to that of any single method, indicating robust diagnostic efficacy. By integrating localized bone metabolism and systemic inflammatory markers, TPBS-CRP provides a dual-dimensional assessment of inflammatory status, thereby enhancing the diagnostic accuracy of PJI. Critically, the simplicity, reliability, and cost-effectiveness of TPBS-CRP make it a practical solution for routine screening, especially in resource-limited settings where advanced imaging studies are unavailable.
It is worth noting that our findings further revealed that patients with false-positive TPBS diagnoses (both TKA and THA cohorts) exhibited significantly greater bone loss and prolonged symptom duration compared to true-negative cases. This aligns with the principle of TPBS, as mechanical loosening or inflammatory bone remodelling at the implant interface triggers localized hyperaemia and accelerated osteoblastic activity, resulting in enhanced radiotracer uptake.27,28 Consequently, severe bone loss and prolonged symptom duration likely underlie the limited diagnostic efficacy of TPBS. Furthermore, TPBS demonstrated superior diagnostic efficiency for prosthetic hip infection compared to prosthetic knee infection. We propose that this discrepancy arises from both prolonged post-TKA tracer uptake patterns and biomechanical alterations induced by knee arthroplasty, which collectively disrupt natural joint kinematics and amplify metabolic heterogeneity around the prosthesis.29,30
Antibiotic therapy effectively suppresses infections but critically compromises the diagnostic utility of traditional biomarkers.31,32 This study found that while antibiotics notably impacts the diagnostic efficacy of CRP, TBS remains unaffected. CRP, a systemic inflammatory marker, directly reflects infection-related immune activation; however, antibiotic-induced suppression of pathogens diminishes systemic inflammation, leading to rapid CRP decline and false-negative interpretations. In contrast, TPBS detects PJI by evaluating localized bone metabolic activity, independent of systemic inflammation. Even partial infection control by antibiotics fails to halt bone remodelling triggered by pre-existing structural damage—osteolysis and mechanical loosening—both of which sustain radiotracer uptake. Furthermore, antibiotics often fail to penetrate bacterial biofilms on implant surfaces,33 allowing residual localized infections to drive persistent metabolic activity detectable by TPBS. These observations align with prior reports linking antibiotics to reduced accuracy of serum and synovial biomarkers in PJI detection.34,35 Our study further highlights the resilience of TPBS in antibiotic-treated patients and underscores the clinical value of combining TPBS (structural assessment) with CRP (systemic inflammation) to enhance diagnostic reliability, particularly in complex cases where antibiotic use is unavoidable.
In addition, our findings reveal joint-specific antibiotic effects on diagnostic accuracy, with antibiotic-treated prosthetic knee infection patients exhibiting significantly lower CRP accuracy than untreated counterparts (79.1% vs 97.1%), whereas in prosthetic hip infection, accuracy was paradoxically higher in the antibiotic group (88.9% vs 59.2%). This contrasts with conventional clinical expectations. However, the discrepancy may stem from the anatomical complexity of the hip joint. The deep-seated hip joint often delays diagnosis until advanced stages, where entrenched infections resist complete eradication despite antibiotic therapy, perpetuating systemic inflammation and elevated CRP levels.
This study has several limitations, including the retrospective design and small sample size, which may introduce bias. Additionally, it was not possible for us to retrieve correct information regarding the onset of PJI. Lastly, this study was conducted at a single centre, so its generalizability to other medical institutions remains uncertain. Future research should aim to increase the sample size and conduct multicentre studies to validate these findings. Despite these limitations, we believe that this study provides an important insight into the diagnosis of PJI by TPBS.
In conclusion, while TPBS demonstrates clinical utility in PJI diagnosis, its suboptimal accuracy limits its role as a standalone diagnostic tool. However, TPBS-CRP addresses this limitation by synergizing localized bone metabolic data with systemic inflammatory profiling, achieving superior diagnostic efficacy while maintaining cost-effectiveness and resistance to antibiotic interference. This dual-dimensional approach proves particularly advantageous in resource-limited settings for PJI screening. Nevertheless, the specificity of the TPBS-CRP requires refinement by integrating clinical parameters, such as bone loss severity, to ensure precise differentiation from aseptic loosening.
Author contributions
Q. Chen: Formal analysis, Investigation, Methodology, Writing – original draft
Y. Li: Formal analysis, Investigation, Methodology
X. Guo: Formal analysis, Investigation, Methodology
W. Wlamu: Formal analysis, Methodology
W. Mu: Formal analysis, Methodology
B. Ji: Formal analysis, Investigation, Methodology
L. Cao: Formal analysis, Methodology, Writing – review & editing
X. Zhang: Formal analysis, Methodology, Writing – review & editing
Funding statement
The author(s) disclose receipt of the following financial or material support for the research, authorship, and/or publication of this article: this work was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous (grant number 2023D01E11); the Natural Science Foundation of Xinjiang Uygur Autonomous Region (grant number 2022D01D56); Major Special project of Science and Technology Program of Xinjiang Uygur Autonomous Region (grant number 2022A03011); "Tianshan Talents" medical and health high-level personnel training program (grant number TSYC202301A008); and National Natural Science Foundation of China (grant number 82160421).
ICMJE COI statement
No conflict of interest exits in the submission of this manuscript, and the final manuscript has been approved by all authors for publication. The work described in the manuscript is original research that has not been published previously, and the manuscript is not under consideration for publication elsewhere, either in whole or in part.
Data sharing
The data that support the findings for this study are available to other researchers from the corresponding author upon reasonable request.
Acknowledgements
Wei Ma, Adila, and Ya Ba contributed to this study by reviewing the three-phase bone scintigraphy images.
Ethical review statement
Ethical approval for this study was obtained from the ethics committee of First Affiliated Hospital of Xinjiang Medical University (K202506-05).
Open access funding
The open access fee for this article was funded by the Natural Science Foundation of Xinjiang Uygur Autonomous Region (grant number 2023D01E11), Major Special project of Science and Technology Program of Xinjiang Uygur Autonomous Region (grant number 2022A03011), and "Tianshan Talents" medical and health high-level personnel training program (grant number TSYC202301A008)
© 2026 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/
Data Availability
The data that support the findings for this study are available to other researchers from the corresponding author upon reasonable request.
References
- 1. Shichman I, Askew N, Habibi A, et al. Projections and epidemiology of revision hip and knee arthroplasty in the United States to 2040-2060. Arthroplast Today. 2023;21:101152. doi: 10.1016/j.artd.2023.101152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Shichman I, Kurapatti M, Roof M, Christensen TH, Rozell JC, Schwarzkopf R. Impact of indication for revision THA on resource utilization. J Arthroplasty. 2022;37(12):2333–2339. doi: 10.1016/j.arth.2022.06.007. [DOI] [PubMed] [Google Scholar]
- 3. Knoll L, Steppacher SD, Furrer H, Thurnheer-Zürcher MC, Renz N. High treatment failure rate in haematogenous compared to non-haematogenous periprosthetic joint infection. Bone Joint J. 2023;105-B(12):1294–1302. doi: 10.1302/0301-620X.105B12.BJJ-2023-0454.R1. [DOI] [PubMed] [Google Scholar]
- 4. Aleksyniene R, Iyer V, Bertelsen HC, et al. The role of nuclear medicine imaging with 18F-FDG PET/CT, combined 111In-WBC/99mTc-Nanocoll, and 99mTc-HDP SPECT/CT in the evaluation of patients with chronic problems after TKA or THA in a prospective study. Diagnostics (Basel) 2022;12(3):681. doi: 10.3390/diagnostics12030681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Hoveidaei A, Tavakoli Y, Ramezanpour MR, et al. Imaging in periprosthetic joint infection diagnosis: a comprehensive review. Microorganisms. 2024;13(1):10. doi: 10.3390/microorganisms13010010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Nie L, Sun Z, Shan F, Li C, Ding X, Shen C. An artificial intelligence framework for the diagnosis of prosthetic joint infection based on 99mTc-MDP dynamic bone scintigraphy. Eur Radiol. 2023;33(10):6794–6803. doi: 10.1007/s00330-023-09687-w. [DOI] [PubMed] [Google Scholar]
- 7. Ottink KD, Gelderman SJ, Wouthuyzen-Bakker M, Ploegmakers JJW, Glaudemans AWJM, Jutte PC. Nuclear imaging does not have clear added value in patients with low a priori chance of periprosthetic joint infection. A retrospective single-center experience. J Bone Jt Infect. 2022;7(1):1–9. doi: 10.5194/jbji-7-1-2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Blanc P, Bonnet E, Giordano G, Monteil J, Salabert AS, Payoux P. The use of labelled leucocyte scintigraphy to evaluate chronic periprosthetic joint infections: a retrospective multicentre study on 168 patients. Eur J Clin Microbiol Infect Dis. 2019;38(9):1625–1631. doi: 10.1007/s10096-019-03587-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Verberne SJ, Sonnega RJA, Temmerman OPP, Raijmakers PG. What is the accuracy of nuclear imaging in the assessment of periprosthetic knee infection? A meta-analysis. Clin Orthop Relat Res. 2017;475(5):1395–1410. doi: 10.1007/s11999-016-5218-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Sigmund IK, Holinka J, Staats K, et al. Inferior performance of established and novel serum inflammatory markers in diagnosing periprosthetic joint infections. Int Orthop. 2021;45(4):837–846. doi: 10.1007/s00264-020-04889-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Della Valle C, Parvizi J, Bauer TW, et al. Diagnosis of periprosthetic joint infections of the hip and knee. J Am Acad Orthop Surg. 2010;18(12):760–770. doi: 10.5435/00124635-201012000-00006. [DOI] [PubMed] [Google Scholar]
- 12. Parvizi J, Zmistowski B, Berbari EF, et al. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011;469(11):2992–2994. doi: 10.1007/s11999-011-2102-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Parvizi J, Fassihi SC, Enayatollahi MA. Diagnosis of periprosthetic joint infection following hip and knee arthroplasty. Orthop Clin North Am. 2016;47(3):505–515. doi: 10.1016/j.ocl.2016.03.001. [DOI] [PubMed] [Google Scholar]
- 14. Parvizi J, Tan TL, Goswami K, et al. The 2018 definition of periprosthetic hip and knee infection: an evidence-based and validated criteria. J Arthroplasty. 2018;33(5):1309–1314. doi: 10.1016/j.arth.2018.02.078. [DOI] [PubMed] [Google Scholar]
- 15. McNally M, Sousa R, Wouthuyzen-Bakker M, et al. The EBJIS definition of periprosthetic joint infection. Bone Joint J. 2021;103-B(1):18–25. doi: 10.1302/0301-620X.103B1.BJJ-2020-1381.R1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Khan Y, Arora S, Kashyap A, Patralekh MK, Maini L. Bone defect classifications in revision total knee arthroplasty, their reliability and utility: a systematic review. Arch Orthop Trauma Surg. 2023;143(1):453–468. doi: 10.1007/s00402-022-04517-y. [DOI] [PubMed] [Google Scholar]
- 17. Paprosky WG, Perona PG, Lawrence JM. Acetabular defect classification and surgical reconstruction in revision arthroplasty. A 6-year follow-up evaluation. J Arthroplasty. 1994;9(1):33–44. doi: 10.1016/0883-5403(94)90135-x. [DOI] [PubMed] [Google Scholar]
- 18. Paprosky WG, Burnett RS. Assessment and classification of bone stock deficiency in revision total hip arthroplasty. Am J Orthop. 2002;31(8):459–464. [PubMed] [Google Scholar]
- 19. Van den Wyngaert T, Strobel K, Kampen WU, et al. The EANM practice guidelines for bone scintigraphy. Eur J Nucl Med Mol Imaging. 2016;43(9):1723–1738. doi: 10.1007/s00259-016-3415-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Gehrke T, Citak M, Parvizi J, Budhiparama NC, Akkaya M. Periprosthetic joint infections: state-of-the-art. Arch Orthop Trauma Surg. 2024;145(1):58. doi: 10.1007/s00402-024-05627-5. [DOI] [PubMed] [Google Scholar]
- 21. Zhou H, Yang Y, Zhang Y, et al. Current status and perspectives of diagnosis and treatment of periprosthetic joint infection. Infect Drug Resist. 2024;17:2417–2429. doi: 10.2147/IDR.S457644. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Tarabichi S, Goh GS, Fraval A, et al. Serum and synovial markers in the diagnosis of periprosthetic joint infection of the hip, knee, and shoulder: an algorithmic approach. J Bone Joint Surg Am. 2024;106-A(13):1221–1230. doi: 10.2106/JBJS.23.00669. [DOI] [PubMed] [Google Scholar]
- 23. Hofmann UK, Eleftherakis G, Migliorini F, Fink B, Mederake M. Diagnostic and prognostic relevance of plain radiographs for periprosthetic joint infections of the hip: a literature review. Eur J Med Res. 2024;29(1):314. doi: 10.1186/s40001-024-01891-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Leal J, Holland CT, Cochrane NH, et al. The relationship between pseudotumours and infected complications in patients who have undergone metal-on-metal total hip arthroplasty. Bone Joint J. 2024;106-B(6):555–564. doi: 10.1302/0301-620X.106B6.BJJ-2023-1370.R1. [DOI] [PubMed] [Google Scholar]
- 25. Hill DS, Kinsella D, Toms AD. Three-phase Technetium-99m bone scanning in patients with pain in the knee region after cemented total knee arthroplasty. Eur J Orthop Surg Traumatol. 2019;29(5):1105–1113. doi: 10.1007/s00590-019-02407-5. [DOI] [PubMed] [Google Scholar]
- 26. Hill DS, Naim S, Powell RJ, Kinsella D, Toms AD, Howell J. 3-phase Technicium-99m bone scanning in patients with pain in the hip region after cemented total hip replacement: a multicentre series of 100 cases. Hip Int. 2018;28(3):259–265. doi: 10.5301/hipint.5000572. [DOI] [PubMed] [Google Scholar]
- 27. Harnik MA, Sodmann A, Hartmannsberger B, et al. Bone metabolism in complex regional pain syndrome. Pain Rep. 2024;9(6):e1217. doi: 10.1097/PR9.0000000000001217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Mandegaran R, Agrawal K, Vijayanathan S, Gnanasegaran G. The value of 99mTc-MDP bone SPECT/CT in evaluation of patients with painful knee prosthesis. Nucl Med Commun. 2018;39(5):397–404. doi: 10.1097/MNM.0000000000000825. [DOI] [PubMed] [Google Scholar]
- 29. Niccoli G, Mercurio D, Cortese F. Bone scan in painful knee arthroplasty: obsolete or actual examination? Acta Biomed. 2017;88(2S):68–77. doi: 10.23750/abm.v88i2-S.6516. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Zhang F, Shen C, Yu J, et al. The temporal impact of prosthesis implantation and semi-quantitative criteria on the diagnostic efficacy of triple-phase bone scanning for periprosthetic joint infection. Orthop Surg. 2022;14(7):1438–1446. doi: 10.1111/os.13278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Zou C, Guo W, Mu W, et al. Synovial vancomycin and meropenem concentrations in periprosthetic joint infection treated by single-stage revision combined with intra-articular infusion. Bone Joint Res. 2024;13(10):535–545. doi: 10.1302/2046-3758.1310.BJR-2024-0024.R2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Moore AJ, Wylde V, Whitehouse MR, et al. Development of evidence-based guidelines for the treatment and management of periprosthetic hip infection. Bone Jt Open. 2023;4(4):226–233. doi: 10.1302/2633-1462.44.BJO-2022-0155.R1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Roy R, Tiwari M, Donelli G, Tiwari V. Strategies for combating bacterial biofilms: a focus on anti-biofilm agents and their mechanisms of action. Virulence. 2018;9(1):522–554. doi: 10.1080/21505594.2017.1313372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Salimy MS, Blackburn AZ, Katakam A, Bedair HS, Melnic CM. Utility of diagnostic markers in late periprosthetic joint infection workup for total knee arthroplasty patients who received antibiotics 48 hours before aspiration. J Arthroplasty. 2023;38(9):1854–1860. doi: 10.1016/j.arth.2023.03.010. [DOI] [PubMed] [Google Scholar]
- 35. Dugdale EM, Uvodich ME, Osmon DR, Pagnano MW, Berry DJ, Abdel MP. Recent antibiotic treatment impacts serum and synovial laboratory values in early periprosthetic joint infection workup. J Arthroplasty. 2022;37(6S):S286–S290. doi: 10.1016/j.arth.2022.02.064. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings for this study are available to other researchers from the corresponding author upon reasonable request.




