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Is 18F-fluoride PET/CT an Accurate Tool to Diagnose Loosening After Total Joint Arthroplasty?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics and Handsurgery.ORCID iD: 0000-0002-2583-5448
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Molecular imaging and medical physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.ORCID iD: 0000-0001-5738-9983
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics and Handsurgery.ORCID iD: 0000-0002-3600-253x
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics and Handsurgery.ORCID iD: 0000-0002-3233-2638
2025 (English)In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 483, no 3, p. 415-428Article in journal (Refereed) Published
Abstract [en]

Background 

Several studies using positron emission tomography (PET) show highly elevated periprosthetic bone uptake of fluorine-18 sodium fluoride (18F-fluoride), suggestive of implant loosening after arthroplasty. Focus so far has been on qualitative but not on quantitative assessment. There is also a lack of intraoperative confirmation of preoperative 18F-fluoride PET findings. Although the method seems to have acceptable accuracy and high sensitivity, an attempt to improve the specificity and an overall validation of the method appear warranted.

Questions/purposes 

(1) Is there a difference in 18F-fluoride uptake around loose versus well-fixed THA and TKA components? (2) Can 18F-fluoride uptake measures provide a threshold that differentiates loose from well-fixed implants undergoing revision for a variety of septic and aseptic indications? (3) In a population restricted to THA and TKA undergoing revision for aseptic indications, can measurement of 18F-fluoride uptake still distinguish loose from well-fixed components? (4) What is the interrater reliability of measuring 18F-fluoride uptake?

Methods 

This was a retrospective assessment of a diagnostic test, 18F-fluoride PET/CT, which was performed prior to revision surgery. We included 63 patients with 31 THAs and 32 TKAs. Sixty-five percent of patients were female, and the mean age at 18F-fluoride PET/CT was 66 years. The THA had different modes of fixation (cemented, cementless, and hybrid; 45%, 32%, and 23%, respectively), whereas all TKAs were cemented. Imaging was conducted using routine protocols 1 hour after tracer injection. The interobserver reproducibility was analyzed using Spearman rank correlations and Bland-Altman analyses. Two independent observers were trained separately by a nuclear physician to measure maximal periprosthetic standardized uptake values (SUVmax) for each arthroplasty component (n = 126). Findings at surgery (whether the components were well fixed or loose, as well as the presence or absence of infection) were used as a reference. Presence of periprosthetic joint infection was retrospectively determined based on the criteria suggested by the European Bone and Joint Infection Society (EBJIS): clinical features in combination with blood analysis, synovial fluid cytologic analysis, and microbiology test results. Receiver operating characteristic (ROC) curves were plotted to assess the area under the curve (AUC) for each investigated component separately, indicating suitable SUVmax thresholds that differentiate loose from well-fixed components. After excluding patients with confirmed or suspected PJI per the EBJIS criteria (n = 12), the above analysis was repeated for the remaining patients with aseptic loosening (n = 51).

Results 

We found higher 18F-fluoride uptake around loose versus well-fixed components in all but femoral TKA components (median [range] SUVmax for well-fixed versus loose THA cups 10 [7 to 30] versus 22 [6 to 64], difference of medians 12; p = 0.003; well-fixed versus loose TKA femoral components 14 [4 to 41] versus 19 [9 to 42], difference of medians 5; p = 0.38). We identified favorable ROC curves for all investigated components except femoral TKA components (THA cups AUC 0.81 [best threshold 13.9]; THA femoral stems AUC 0.9 [best threshold 17.3]; femoral TKA components AUC 0.6 [best threshold 14.3]; tibial TKA components AUC 0.83 [best threshold 15.8]). 18F-fluoride was even more accurate at diagnosing loosening when we limited the population to those patients believed not to have prosthetic joint infection (THA cups AUC 0.87 [best threshold 14.2]; THA femoral stems AUC 0.93 [best threshold 15.0]; femoral TKA components AUC 0.65 [best threshold 15.8]; tibial TKA components AUC 0.86 [best threshold 14.7]). We found strong interrater correlation when assessing SUVmax values, with Spearman ρ values ranging from 0.96 to 0.99 and Bland-Altman plots indicating excellent agreement between the two independent observers.

Conclusion 

Measuring SUVmax after 18F-fluoride PET/CT is a useful adjunct in the diagnostic evaluation for suspected implant loosening after THA and TKA. The method appears to be both accurate and reliable in diagnosing implant loosening for all components except femoral TKA components. In a real-world mixed population with both low-grade infection and aseptic loosening, the method seems to be fairly easy to learn and helpful to subspecialized arthroplasty clinicians. When infection can be ruled out, the method probably performs even better. Further prospective studies are warranted to explore the reason why femoral TKA component loosening was more difficult to ascertain using this novel technique.

Level of Evidence 

Level III, diagnostic study.

Place, publisher, year, edition, pages
Wolters Kluwer, 2025. Vol. 483, no 3, p. 415-428
National Category
Orthopaedics Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-538680DOI: 10.1097/corr.0000000000003228ISI: 001434181600013PubMedID: 39293088Scopus ID: 2-s2.0-85205531156OAI: oai:DiVA.org:uu-538680DiVA, id: diva2:1899089
Part of project
Dual-mobility cups: Double safety for patients with a femoral neck fracture?, Swedish Research CouncilPredict and prevent early hip arthroplasty complications, Swedish Research Council
Funder
Swedish Research Council, 2019-00436Swedish Research Council, 2021-00980Erik, Karin och Gösta Selanders FoundationSwedish Heart Lung FoundationAvailable from: 2024-09-19 Created: 2024-09-19 Last updated: 2026-02-22Bibliographically approved
In thesis
1. Dynamics of Periprosthetic Bone Metabolism: Biological Responses to Denosumab and the Clinical Utility of Metabolic PET/CT Imaging
Open this publication in new window or tab >>Dynamics of Periprosthetic Bone Metabolism: Biological Responses to Denosumab and the Clinical Utility of Metabolic PET/CT Imaging
2026 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In four studies, this thesis investigates periprosthetic bone metabolism and the clinical utility of advanced imaging in total joint arthroplasty, with the overall aim of evaluating the biological and densitometric effects of pharmacological bone modulation following total hip arthroplasty (THA) and assessing the diagnostic performance of positron emission tomography/computed tomography (PET/CT) in evaluating painful hip and knee arthroplasties.

Study I examined systemic immunological and bone-related biomarkers after denosumab treatment following THA, finding that denosumab was linked to significant upregulation of receptor activator of nuclear factor κB ligand (RANKL) and reduced expression of tumour necrosis factor receptor superfamily member 9 (TNFRSF9), suggesting compensatory osteoclastogenesis stimulation potentially driving the ‘rebound phenomenon’ observed after treatment discontinuation.

Study II evaluated the long-term impact of denosumab on periprosthetic bone mineral density (pBMD) following THA. At the five-year postoperative follow-up, no significant differences in femoral or acetabular pBMD were observed between the denosumab and placebo groups. These findings suggest that early densitometric benefits of short-term antiresorptive therapy are transient and do not confer sustained protection against periprosthetic bone loss in this population.

Study III assessed the diagnostic accuracy of fluorine-18 sodium fluoride (18F-fluoride) PET/CT for detecting aseptic loosening in painful hip and knee arthroplasties. The technique demonstrated high accuracy and reproducibility, particularly for THA, but its performance was reduced for certain components in total knee arthroplasty.

Study IV compared 18F-fluorodeoxyglucose (18F-FDG) and 18F-fluoride PET/CT for diagnosing periprosthetic joint infection (PJI) using EBJIS criteria as the reference standard. 18F-FDG PET/CT demonstrated superior diagnostic accuracy, especially for THA stems and tibial components in knee arthroplasties, whereas 18F-fluoride PET/CT showed limited discriminatory capacity. Quantitative SUVmax measurements were reproducible across most implant components, supporting their potential role in standardised diagnostic assessment.

In conclusion, short-term denosumab treatment failed to confer sustained preservation of periprosthetic bone after THA. It may induce biological responses—specifically, RANKL upregulation—that contribute to rapid bone loss after treatment discontinuation. PET/CT offers valuable diagnostic support in painful arthroplasties, with 18F-fluoride PET/CT most effective for assessing mechanical loosening and 18F-FDG PET/CT demonstrating superior accuracy for detecting PJI.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2026. p. 128
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2235
Keywords
Periprosthetic bone metabolism, Total joint arthroplasty, Denosumab, Periprosthetic joint infection, PET/CT imaging, Bone mineral density, Diagnostic imaging
National Category
Orthopaedics
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-580203 (URN)978-91-513-2750-1 (ISBN)
Public defence
2026-04-10, Grönwallsalen, Ingång 70, BV, Akademiska Sjukhuset, Sjukhusvägen, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2026-03-18 Created: 2026-02-22 Last updated: 2026-03-18

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Sköld, CarolineSörensen, JensBrüggemann, AndersHailer, Nils P.

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