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Bone & Joint Research
Vol. 13, Issue 12 | Pages 750 - 763
11 Dec 2024
Xie C Gong J Zheng C Zhang J Gao J Tian C Guo X Dai S Gao T

Aims

This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.

Methods

The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 741 - 749
6 Dec 2024
Blichfeldt-Eckhardt MR Varnum C Lauridsen JT Rasmussen LE Mortensen WCP Jensen HI Vaegter HB Lambertsen KL

Aims. Better prediction of outcome after total hip arthroplasty (THA) is warranted. Systemic inflammation and central neuroinflammation are possibly involved in progression of osteoarthritis and pain. We explored whether inflammatory biomarkers in blood and cerebrospinal fluid (CSF) were associated with clinical outcome, and baseline pain or disability, 12 months after THA. Methods. A total of 50 patients from the Danish Pain Research Biobank (DANPAIN-Biobank) between January and June 2018 were included. Postoperative outcome was assessed as change in Oxford Hip Score (OHS) from baseline to 12 months after THA, pain was assessed on a numerical rating scale, and disability using the Pain Disability Index. Multiple regression models for each clinical outcome were included for biomarkers in blood and CSF, respectively, including age, sex, BMI, and Kellgren-Lawrence score. Results. Change in OHS was associated with blood concentrations of tumour necrosis factor (TNF), interleukin-8 (IL-8), interleukin-6 receptor (IL-6R), glycoprotein 130 (gp130), and IL-1β (R. 2. = 0.28, p = 0.006), but not with CSF biomarkers. Baseline pain was associated with blood concentrations of lymphotoxin alpha (LTα), TNFR1, TNFR2, and IL-6R (R. 2. = 0.37, p < 0.001) and CSF concentrations of TNFR1, TNFR2, IL-6, IL-6R, and IL-1Ra (R. 2. = 0.40, p = 0.001). Baseline disability was associated with blood concentrations of TNF, LTα, IL-8, IL-6, and IL-1α (R. 2. = 0.53, p < 0.001) and CSF concentrations of gp130, TNF, and IL-1β (R. 2. = 0.26, p = 0.002). Thus, preoperative systemic low-grade inflammation predicted 12-month postoperative outcome after THA, and was associated with preoperative pain and disability. Conclusion. This study highlights the importance of systemic inflammation in osteoarthritis, and presents a possible path for better patient selection for THA in the future. Preoperative central neuroinflammation was associated with preoperative pain and disability, but not change in OHS after THA. Cite this article: Bone Joint Res 2024;13(12):741–749


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1426 - 1430
1 Dec 2024
Warne CN Ryan S Yu E Osmon DR Berry DJ Abdel MP

Aims

Cutibacterium acnes (C. acnes; previously known as Propionibacterium acnes or P. acnes) periprosthetic hip and knee infections are under-reported. While culture contamination with C. acnes occurs, true infections are important to recognize and treat. We sought to describe the demographics and treatment outcomes of patients with C. acnes periprosthetic joint infections (PJIs) of the hip and knee.

Methods

Patients with C. acnes PJI between January 2005 and December 2018 were retrospectively reviewed utilizing the institutional total joint registry. Patients with monomicrobial PJI and two or more positive cultures were considered to have true C. acnes PJI. Patients with polymicrobial infection or with only one positive culture were excluded. This resulted in 35 PJIs (21 hips and 14 knees); the patients’ mean age was 63 years (35 to 84) and 15 (43%) were female. Mean follow-up was five years (1 to 14).


Bone & Joint 360
Vol. 13, Issue 6 | Pages 33 - 35
1 Dec 2024

The December 2024 Spine Roundup360 looks at: Rostral facet joint violations in robotic- and navigation-assisted pedicle screw placement; The inhibitory effect of non-steroidal anti-inflammatory drugs and opioids on spinal fusion: an animal model;L5-S1 transforaminal lumbar interbody fusion is associated with increased revisions compared to L4-L5 TLIF at two years; Immediate versus gradual brace weaning protocols in adolescent idiopathic scoliosis: a randomized clinical trial; Effectiveness and cost-effectiveness of an individualized, progressive walking, and education intervention for the prevention of low back pain recurrence in Australia (WalkBack): a randomized controlled trial; Usefulness and limitations of intraoperative pathological diagnosis using frozen sections for spinal cord tumours; Effect of preoperative HbA1c and blood glucose level on the surgical site infection after lumbar instrumentation surgery; How good are surgeons at achieving their alignment goals?


Bone & Joint Research
Vol. 13, Issue 11 | Pages 673 - 681
22 Nov 2024
Yue C Xue Z Cheng Y Sun C Liu Y Xu B Guo J

Aims

Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH.

Methods

This cross-sectional study was carried out according to the “STrengthening the Reporting of OBservational studies in Epidemiology” statement. Data on 19 variables were collected at a single timepoint from 250 patients with ONFH who were treated at our medical centre between July and December 2023 using validated instruments or, in the case of hip pain, a numerical rating scale. Factors associated with pain severity were identified using hierarchical multifactor linear regression.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 659 - 672
20 Nov 2024
Mo H Sun K Hou Y Ruan Z He Z Liu H Li L Wang Z Guo F

Aims

Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Methods

A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1216 - 1222
1 Nov 2024
Castagno S Gompels B Strangmark E Robertson-Waters E Birch M van der Schaar M McCaskie AW

Aims

Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials.

Methods

A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims. This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Methods. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610


Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Methods

Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 525 - 534
1 Oct 2024
Mu W Xu B Wang F Maimaitiaimaier Y Zou C Cao L

Aims

This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification.

Methods

We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 513 - 524
19 Sep 2024
Kalsoum R Minns Lowe CJ Gilbert S McCaskie AW Snow M Wright K Bruce G Mason DJ Watt FE

Aims

To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design.

Methods

Healthcare professionals, clinicians, and/or researchers (HCP/Rs) were surveyed, and the data were presented at a congress workshop. A second and related survey was then developed for people with joint damage caused by knee injury and/or osteoarthritis (PJDs), who were approached by a UK Charity newsletter or Oxford involvement registry. Anonymized data were collected and analyzed in Qualtrics.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 474 - 484
10 Sep 2024
Liu Y Li X Jiang L Ma J

Aims

Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

Methods

Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 1021 - 1030
1 Sep 2024
Oto J Herranz R Fuertes M Plana E Verger P Baixauli F Amaya JV Medina P

Aims. Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. Methods. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Results. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain. Cite this article: Bone Joint J 2024;106-B(9):1021–1030


Bone & Joint Research
Vol. 13, Issue 8 | Pages 372 - 382
1 Aug 2024
Luger M Böhler C Puchner SE Apprich S Staats K Windhager R Sigmund IK

Aims. Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. Methods. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test. Results. AGR, CAR, and CRP were associated with PJI (p < 0.001). Sensitivities were 62.5% (95% CI 54.3 to 70.0), 73.6% (95% CI 65.8 to 80.1), and 71.5% (95% CI 63.6 to 78.3), respectively. Specificities were calculated with 84.7% (95% CI 77.5 to 89.9), 86.3% (95% CI 79.2 to 91.2), and 87.8% (95% CI 80.9 to 92.4), respectively. The AUC of CRP (0.797 (95% CI 0.750 to 0.843)) was significantly higher than the AUC of AGR (0.736 (95% CI 0.686 to 0.786), p < 0.001), and similar to AUC of CAR (0.799 (95% CI 0.753 to 0.846), p = 0.832). Decreased sensitivities were observed in PJIs caused by low-virulence organisms (AGR: 60%, CAR: 78%) compared to high-virulence pathogens (AGR: 80%, p = 0.042; CAR: 88%, p = 0.158). Higher sensitivities were seen in acute haematogenous (AGR: 83%, CAR: 96%) compared to chronic PJIs (AGR: 54%, p = 0.001; CAR: 65%, p < 0.001). Conclusion. Serum AGR and CAR showed limited diagnostic accuracy (especially in low-grade and chronic infections) and did not outperform the established marker CRP in our study. Hence, neither parameter can be recommended as an additional tool for diagnosing PJI. Cite this article: Bone Joint Res 2024;13(8):372–382


The Bone & Joint Journal
Vol. 106-B, Issue 8 | Pages 802 - 807
1 Aug 2024
Kennedy JW Sinnerton R Jeyakumar G Kane N Young D Meek RMD

Aims

The number of revision arthroplasties being performed in the elderly is expected to rise, including revision for infection. The primary aim of this study was to measure the treatment success rate for octogenarians undergoing revision total hip arthroplasty (THA) for periprosthetic joint infection (PJI) compared to a younger cohort. Secondary outcomes were complications and mortality.

Methods

Patients undergoing one- or two-stage revision of a primary THA for PJI between January 2008 and January 2021 were identified. Age, sex, BMI, American Society of Anesthesiologists grade, Charlson Comorbidity Index (CCI), McPherson systemic host grade, and causative organism were collated for all patients. PJI was classified as ‘confirmed’, ‘likely’, or ‘unlikely’ according to the 2021 European Bone and Joint Infection Society criteria. Primary outcomes were complications, reoperation, re-revision, and successful treatment of PJI. A total of 37 patients aged 80 years or older and 120 patients aged under 80 years were identified. The octogenarian group had a significantly lower BMI and significantly higher CCI and McPherson systemic host grades compared to the younger cohort.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 362 - 371
17 Jul 2024
Chang H Liu L Zhang Q Xu G Wang J Chen P Li C Guo X Yang Z Zhang F

Aims

The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA.

Methods

Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 342 - 352
9 Jul 2024
Cheng J Jhan S Chen P Hsu S Wang C Moya D Wu Y Huang C Chou W Wu K

Aims

To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

Methods

The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims

Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods

Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.


Bone & Joint Open
Vol. 5, Issue 6 | Pages 479 - 488
6 Jun 2024
Paksoy A Meller S Schwotzer F Moroder P Trampuz A Imiolczyk J Perka C Hackl M Plachel F Akgün D

Aims. Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients. Methods. This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline. Results. Overall, several miRNAs in plasma and tissue were identified to be progressively deregulated according to ongoing PJI. When comparing the plasma samples, patients with a high-grade infection showed significantly higher expression levels for hsa-miR-21-3p, hsa-miR-1290, and hsa-miR-4488, and lower expression levels for hsa-miR-130a-3p and hsa-miR-451a compared to the aseptic group. Furthermore, the high-grade group showed a significantly higher regulated expression level of hsa-miR-1260a and lower expression levels for hsa-miR-26a-5p, hsa-miR-26b-5p, hsa-miR-148b-5p, hsa-miR-301a-3p, hsa-miR-451a, and hsa-miR-454-3p compared to the low-grade group. No significant differences were found between the low-grade and aseptic groups. When comparing the tissue samples, the high-grade group showed significantly higher expression levels for 23 different miRNAs and lower expression levels for hsa-miR-2110 and hsa-miR-3200-3p compared to the aseptic group. No significant differences were found in miRNA expression between the high- and low-grade groups, as well as between the low-grade and aseptic groups. Conclusion. With this prospective pilot study, we were able to identify a circulating miRNA signature correlating with high-grade PJI compared to aseptic patients undergoing hip arthroplasty revision. Our data contribute to establishing miRNA signatures as potential novel diagnostic and prognostic biomarkers for PJI. Cite this article: Bone Jt Open 2024;5(6):479–488


Bone & Joint Research
Vol. 13, Issue 6 | Pages 261 - 271
1 Jun 2024
Udomsinprasert W Mookkhan N Tabtimnark T Aramruang T Ungsudechachai T Saengsiwaritt W Jittikoon J Chaikledkaew U Honsawek S

Aims. This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. Methods. A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry. Results. COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that COMP mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative COMP mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, COMP mRNA expression was considerably up-regulated in a time-dependent manner. Conclusion. All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods. Cite this article: Bone Joint Res 2024;13(6):261–271