Low‐level increases in serum C‐reactive protein are present in early osteoarthritis of the knee and predict progressive disease
Abstract
Objective To examine the role of low-grade inflammation in the etiology and progression of early osteoarthritis (OA) of the knee. Methods We used a new, high-sensitivity, automated monoclonal antibody immunoassay for the classic acute-phase protein, C-reactive protein (CRP), in serum. Anteroposterior radiographs of the knee with weight bearing were obtained on 845 women (ages 44-67) on entry into a population-based study of OA in Chingford, North London. In those defined radiologically as "cases," the knee radiographs were repeated after 4 years. Results Levels of CRP were higher in 105 women with knee OA defined radiologically as Kellgren-Lawrence grade 2+ (median 2.4 mg/liter, interquartile range [IQR] 1.0-5.1), compared with 740 women without OA (median 0.7 mg/liter, IQR 0.3-1.8) (P Conclusion CRP levels are modestly but significantly increased in women with early knee OA, and higher levels predict those whose disease will progress over 4 years, suggesting that low-grade inflammation may be a significant aspect of early OA and may be amenable to therapeutic intervention and secondary prevention.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IL-6 levels in OA fluid correlate with pain, synovial proliferation, and cartilage degradation indicators and control cartilage and bone metabolism.
“By MMP induction and RANKL/OPG axis control, IL-6 levels in OA fluid correlate with pain, synovial proliferation, and cartilage degradation indicators and control cartilage and bone metabolism [48,49].”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [49]
Cited by
Sorted by citations
Acute-Phase Proteins and Other Systemic Responses to Inflammation
Gabay, C., & Kushner, I. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400607 · Cited by 6,734 · see citing works
The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis
Sellam, J., & Berenbaum, F. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.159 · Cited by 1,500 · see citing works
Garnero, P., Piperno, M., Gineyts, E., Christgau, S., Delmas, P. D., & Vignon, E. (2001) · Annals of the Rheumatic Diseases · doi:10.1136/ard.60.6.619 · Cited by 475 · see citing works
Nicklas, B. J., Ambrosius, W., Messier, S. P., Miller, G. D., Penninx, B. W., Loeser, R. F., Palla, S., Bleecker, E., & Pahor, M. (2004) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/79.4.544 · Cited by 443 · see citing works
Taaffe, D. R., Harris, T. B., Ferrucci, L., Rowe, J., & Seeman, T. E. (2000) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/55.12.m709 · Cited by 438 · see citing works
Osteoarthritis, obesity and weight loss: evidence, hypotheses and horizons - a scoping review
Bliddal, H., Leeds, A. R., & Christensen, R. (2014) · Obesity Reviews · doi:10.1111/obr.12173 · Cited by 380 · see citing works
Richardson, D., Pearson, R. G., Kurian, N., Latif, M. L., Garle, M. J., Barrett, D. A., Kendall, D. A., Scammell, B. E., Reeve, A. J., & Chapman, V. (2008) · Arthritis Research & Therapy · doi:10.1186/ar2401 · Cited by 303 · see citing works
Aberrant mitochondrial homeostasis in the skeletal muscle of sedentary older adults
Safdar, A., Hamadeh, M. J., Kaczor, J. J., Raha, S., deBeer, J., & Tarnopolsky, M. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010778 · Cited by 217 · see citing works
Prins, B. P., Abbasi, A., Wong, A., Vaez, A., Nolte, I., Franceschini, N., Stuart, P. E., Guterriez Achury, J., Mistry, V., Bradfield, J. P., et al. (2016) · PLOS Medicine · doi:10.1371/journal.pmed.1001976 · Cited by 199 · see citing works
Self-citationC-Reactive Protein and High-Sensitivity C-Reactive Protein: An Update for Clinicians
Windgassen, E. B., Funtowicz, L., Lunsford, T. N., Harris, L. A., & Mulvagh, S. L. (2011) · Postgraduate Medicine · doi:10.3810/pgm.2011.01.2252 · Cited by 170 · see citing works
Periodontal therapy and cardiovascular risk
Orlandi, M., Graziani, F., & D'Aiuto, F. (2020) · Periodontology 2000 · doi:10.1111/prd.12299 · Cited by 155 · see citing works
Transforming growth factor-β and inflammation in vascular (type IV) Ehlers-Danlos syndrome
Morissette, R., Schoenhoff, F., Xu, Z., Shilane, D. A., Griswold, B. F., Chen, W., Yang, J., Zhu, J., Fert-Bober, J., Sloper, L., et al. (2014) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.113.000280 · Cited by 51 · see citing works
Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders
Schmidt, A. F., Finan, C., Chopade, S., Ellmerich, S., Rossor, M. N., Hingorani, A. D., & Pepys, M. B. (2024) · Open Biology · doi:10.1098/rsob.230419 · Cited by 11 · see citing works
“By contrast, osteoarthritis [63] and lupus [64], respectively, have well-established positive and negative clinical links with CRP, and, interestingly, both were associated with circulating CRP concentrations in the corresponding directions in the current analysis (figure 5).”
Self-citationBiomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease
Kumar, R., Sporn, K., Borole, A., Khanna, A., Gowda, C., Paladugu, P., Ngo, A., Jagadeesan, R., Zaman, N., & Tavakkoli, A. (2025) · Diagnostics · doi:10.3390/diagnostics15111418 · Cited by 10 · see citing works
“By MMP induction and RANKL/OPG axis control, IL-6 levels in OA fluid correlate with pain, synovial proliferation, and cartilage degradation indicators and control cartilage and bone metabolism [48,49].”
- Authors
- Spector, T. D., Hart, D. J., Nandra, D., Doyle, D. V., Mackillop, N., Gallimore, J. R., & Pepys, M. B.
- Affiliations
- St Thomas' Hospital (GB)
- Whipps Cross University Hospital (GB)
- Pfizer (United Kingdom) (GB)
- Hammersmith Hospital (GB)
- Corresponding author
- Spector, T. D.
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 1997-04
- Volume
- 40
- Issue
- 4
- Pages
- 723-727
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2028591423
- Cited by
- 403
- References
- 0
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 5 · 2023: 13 · 2022: 13 · 2021: 7 · 2020: 13 · 2019: 11 · 2018: 11 · 2017: 14 · 2016: 13 · 2015: 19 · 2014: 13 · 2013: 16 · 2012: 15
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Versus Arthritis (17489)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Keywords
- C-reactive protein, knee osteoarthritis, low-grade inflammation, disease progression, early osteoarthritis, Kellgren-Lawrence grade, high-sensitivity CRP, women, joint space narrowing, osteophytes, secondary prevention
- MeSH terms
- Adult, Aged, Antibodies, Monoclonal, Autoanalysis, C-Reactive Protein, Disability Evaluation, Female, Humans, Immunoassay, Knee Joint, Middle Aged, Osteoarthritis, Radiography, Reproducibility of Results, Biomarkers, Disease Progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
