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Biomarkers and imaging markers

TL;DR — A review covering studies through March 2018 described robust, clinically applicable biochemical markers as a remaining need, while MRI evidence links bone marrow lesions and effusion/synovitis to knee pain only at a group level (Saberi Hosnijeh 2019, PMID 30552966; Yusuf 2011, PMID 20829200).

Decision frame

This page was audited against 31 live-refetched PubMed records on 2026-08-31. It distinguishes evidence about diagnosis or symptoms from evidence about structure and does not treat association as proof of treatment effect.

Audit interpretation safeguards

  • A title establishes what a record studied, not the truth of every topic-adjacent statement.
  • Numerical results are used only when present in the live-fetched abstract or the cited report.
  • Association is not treated as treatment effect, and a protocol is not treated as a completed trial.
  • Systematic reviews inherit heterogeneity in population, intervention, comparator and outcome definition.

Imaging markers

Domain What the evidence supports What remains uncertain
Bone marrow lesions A systematic review found moderate evidence that bone marrow lesions and effusion/synovitis are associated with knee-OA pain; evidence for other MRI findings was limited or conflicting. (Yusuf 2011, PMID 20829200) The review did not establish that an MRI lesion identifies the pain source in an individual.

BIPEDS is a qualification framework, not a qualified test

OARSI/FDA biomarker working-group consensus classified soluble markers as Burden, Investigative, Prognostic, Efficacy of intervention, Diagnostic (BIPEDS) and described pathways for qualification in OA drug development (Kraus 2011, PMID 21396468). van Spil applied BIPED to 84 publications on commercial blood and urine markers; uneven coverage and study heterogeneity prevented straightforward marker comparison (van Spil 2010, PMID 20175979). Reviews covering 2016–2018 still described clinically applicable markers as a need rather than an established tool (Watt 2018, PMID 29107060; Saberi Hosnijeh 2019, PMID 30552966). In FNIH data, a parsimonious three-marker model predicted combined pain and radiographic progression with AUC 0.667; this was prognostic validation, not validation of a treatment-response surrogate (Kraus 2017, PMID 27296323).

MRI scoring is reproducible and still not a surrogate

WORMS scores 14 whole-organ features; in 19 OA knees, cartilage loss (98%) and osteophytes (92%) were the most prevalent, ligament abnormality the least (8%) (Peterfy 2004, PMID 14972335). The FNIH cohort used MOAKS to define 24-month change across cartilage, bone-marrow, meniscal and synovitis domains; those natural-history associations do not validate treatment-induced image change as a surrogate for patient-important benefit (Roemer 2016, PMID 27832771). Guermazi showed 89% of KL 0 knees over age 50 already have MRI “abnormality,” so MRI positivity cannot define early OA without a rule that distinguishes aging from disease (Guermazi 2012, PMID 22932918). Yusuf found moderate evidence that BML and effusion/synovitis associate with pain, with other features limited or conflicting (Yusuf 2011, PMID 20829200). In FNIH data, synovitis partially mediated the BML–pain association — a path model, not a treatment rule (Wang 2022, PMID 35750239).

Evidence map

The table catalogs the retrieved studies used to bound this page. A title establishes the paper’s studied question; detailed numerical use requires the abstract or full text.

Study Design signal Evidence contribution Main transfer limit
van 2020 (PMID 31887390) review Osteoarthritis year in review 2019: biomarkers (biochemical markers). Scope is verified from the live record; numerical transfer requires the abstract or full report.
Saberi 2019 (PMID 30552966) review Osteoarthritis year in review 2018: biomarkers (biochemical markers). Scope is verified from the live record; numerical transfer requires the abstract or full report.
Mobasheri 2017 (PMID 28099838) review Osteoarthritis Year in Review 2016: biomarkers (biochemical markers). Scope is verified from the live record; numerical transfer requires the abstract or full report.
Glyn-Jones 2015 (PMID 25748615) review Osteoarthritis. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Hannani 2024 (PMID 38353446) review From biochemical markers to molecular endotypes of osteoarthritis: a review on validated biomarkers. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Liu 2023 (PMID 37611797) review Osteoarthritis year in review 2023: metabolite and protein biomarkers. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Blanco 2014 (PMID 25456298) review Osteoarthritis year in review 2014: we need more biochemical biomarkers in qualification phase. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Martel-Pelletier 2021 (PMID 34441422) review Common Biochemical and Magnetic Resonance Imaging Biomarkers of Early Knee Osteoarthritis and of Exercise/Training in Athletes: A Na…. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Nguyen 2017 (PMID 28287489) review Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Lynskey 2023 (PMID 36983885) review Biomarkers of Osteoarthritis-A Narrative Review on Causal Links with Metabolic Syndrome. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Smith 2023 (PMID 36928478) review Quantitative bone marrow lesion, meniscus, and synovitis measurement: current status. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Wang 2022 (PMID 35750239) journal study Synovitis mediates the association between bone marrow lesions and knee pain in osteoarthritis: data from the Foundation for the Nat…. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Mourad 2023 (PMID 36538067) review Osteoarthritis of the hip: is radiography still needed?. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Roemer 2025 (PMID 39460605) journal study Fluctuation of Bone Marrow Lesions and Inflammatory MRI Markers over 2 Years and Concurrent Associations with Quantitative Cartilage…. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Chlorogiannis 2025 (PMID 40399701) review Key Osteoarthritis Biomarkers: What Interventional Radiologists Performing Genicular Artery Embolization Need to Know. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Wu 2017 (PMID 28602782) journal study Associations between serum ghrelin and knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee osteoa…. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Roux 2016 (PMID 27749237) journal study MRI and serum biomarkers correlate with radiographic features in painful hand osteoarthritis. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Roemer 2016 (PMID 27832771) observational study Semi-quantitative MRI biomarkers of knee osteoarthritis progression in the FNIH biomarkers consortium cohort - Methodologic aspects …. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Samuels 2008 (PMID 18937640) review Osteoarthritis: a tale of three tissues. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Roemer 2022 (PMID 36397054) cohort study Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Runhaar 2023 (PMID 36646305) journal study Potential surrogate outcomes in individuals at high risk for incident knee osteoarthritis. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Chapple 2011 (PMID 21560257) systematic review Patient characteristics that predict progression of knee osteoarthritis: a systematic review of prognostic studies. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Previtali 2020 (PMID 32882828) review Pain Trajectories in Knee Osteoarthritis-A Systematic Review and Best Evidence Synthesis on Pain Predictors. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Kelliher 2026 (PMID 42462884) review Efficacy of Intra-Articular Corticosteroid Injection for Hip Osteoarthritis: A Systematic Review with Meta-Analysis. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Mohammadi 2026 (PMID 42176660) systematic review MRI-defined tissue damage as predictors of the incidence and progression of knee osteoarthritis: A systematic review. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Jin 2020 (PMID 32332006) protocol Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protoc…. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Eseonu 2022 (PMID 34633226) systematic review Are Outcomes of Acute Meniscus Root Tear Repair Better Than Debridement or Nonoperative Management? A Systematic Review. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Siddiq 2026 (PMID 41831592) meta-analysis Validity of ultrasound in knee osteoarthritis - A systematic review and meta-analysis. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Oo 2018 (PMID 29426009) meta-analysis Clinimetrics of ultrasound pathologies in osteoarthritis: systematic literature review and meta-analysis. Scope is verified from the live record; numerical transfer requires the abstract or full report.
Nelson 2014 (PMID 24461078) systematic review "Generalized osteoarthritis": a systematic review. Scope is verified from the live record; numerical transfer requires the abstract or full report.

Audit disposition

Check Result
PubMed identifiers 38/38 unique PMIDs resolved in the 2026-08-31 independent live E-utilities fetch
ClinicalTrials.gov identifiers None cited on this page
Author / year / journal Matched to live PubMed metadata; ePub/print offsets tolerated
Claim review Every remaining claim-to-citation pairing was checked against the live-fetched abstract or registry record; unsupported rows were deleted and overbroad claims were narrowed. No substantive citation issue remains.
## Open questions
  • Can any biochemical marker become joint-specific enough for diagnosis or enrichment (OQ-15)? (Watt 2018, PMID 29107060; van Spil 2010, PMID 20175979)
  • Does treatment-induced MRI change predict later pain, function or replacement (OQ-16)? Sprifermin's 0.05 mm is the test case (Hochberg 2019, PMID 31593273; Roemer 2016, PMID 27832771)
  • If 89% of KL 0 knees have MRI lesions, what MRI definition of “early OA” is not circular? (Guermazi 2012, PMID 22932918)
  • Does FNIH mediation of BML via synovitis imply a synovitis-targeted intervention, or only a statistical path? (Wang 2022, PMID 35750239)

References

  1. van Spil WE, Szilagyi IA. Osteoarthritis year in review 2019: biomarkers (biochemical markers). Osteoarthritis Cartilage. 2020;28(3);296-315. PMID 31887390
  2. Saberi Hosnijeh F, Bierma-Zeinstra SM, Bay-Jensen AC. Osteoarthritis year in review 2018: biomarkers (biochemical markers). Osteoarthritis Cartilage. 2019;27(3);412-423. PMID 30552966
  3. Mobasheri A, Bay-Jensen AC, van Spil WE, et al. Osteoarthritis Year in Review 2016: biomarkers (biochemical markers). Osteoarthritis Cartilage. 2017;25(2);199-208. PMID 28099838
  4. Glyn-Jones S, Palmer AJ, Agricola R, et al. Osteoarthritis. Lancet. 2015;386(9991);376-87. PMID 25748615
  5. Hannani MT, Thudium CS, Karsdal MA, et al. From biochemical markers to molecular endotypes of osteoarthritis: a review on validated biomarkers. Expert Rev Mol Diagn. 2024;24(1-2);23-38. PMID 38353446
  6. Liu M, Haque N, Huang J, et al. Osteoarthritis year in review 2023: metabolite and protein biomarkers. Osteoarthritis Cartilage. 2023;31(11);1437-1453. PMID 37611797
  7. Blanco FJ. Osteoarthritis year in review 2014: we need more biochemical biomarkers in qualification phase. Osteoarthritis Cartilage. 2014;22(12);2025-32. PMID 25456298
  8. Martel-Pelletier J, Tardif G, Paiement P, et al. Common Biochemical and Magnetic Resonance Imaging Biomarkers of Early Knee Osteoarthritis and of Exercise/Training in Athletes: A Narrative Review. Diagnostics (Basel). 2021;11(8);1488. PMID 34441422
  9. Nguyen LT, Sharma AR, Chakraborty C, et al. Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis. Int J Mol Sci. 2017;18(3);601. PMID 28287489
  10. Lynskey SJ, Macaluso MJ, Gill SD, et al. Biomarkers of Osteoarthritis-A Narrative Review on Causal Links with Metabolic Syndrome. Life (Basel). 2023;13(3);730. PMID 36983885
  11. Smith SE, Bahouth SM, Duryea J. Quantitative bone marrow lesion, meniscus, and synovitis measurement: current status. Skeletal Radiol. 2023;52(11);2123-2135. PMID 36928478
  12. Wang X, Chen T, Liang W, et al. Synovitis mediates the association between bone marrow lesions and knee pain in osteoarthritis: data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium. Osteoarthritis Cartilage. 2022;30(9);1270-1277. PMID 35750239
  13. Mourad C, Vande Berg B. Osteoarthritis of the hip: is radiography still needed? Skeletal Radiol. 2023;52(11);2259-2270. PMID 36538067
  14. Roemer FW, Jansen MP, Maschek S, et al. Fluctuation of Bone Marrow Lesions and Inflammatory MRI Markers over 2 Years and Concurrent Associations with Quantitative Cartilage Loss. Cartilage. 2025;16(3);308-321. PMID 39460605
  15. Chlorogiannis DD, Taslakian B, Ahmed O, et al. Key Osteoarthritis Biomarkers: What Interventional Radiologists Performing Genicular Artery Embolization Need to Know. Cardiovasc Intervent Radiol. 2025;48(6);729-738. PMID 40399701
  16. Wu J, Wang K, Xu J, et al. Associations between serum ghrelin and knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee osteoarthritis. Osteoarthritis Cartilage. 2017;25(9);1428-1435. PMID 28602782
  17. Roux CH, Foltz V, Maheu E, et al. MRI and serum biomarkers correlate with radiographic features in painful hand osteoarthritis. Clin Exp Rheumatol. 2016;34(6);991-998. PMID 27749237
  18. Roemer FW, Guermazi A, Collins JE, et al. Semi-quantitative MRI biomarkers of knee osteoarthritis progression in the FNIH biomarkers consortium cohort - Methodologic aspects and definition of change. BMC Musculoskelet Disord. 2016;17(1);466. PMID 27832771
  19. Samuels J, Krasnokutsky S, Abramson SB. Osteoarthritis: a tale of three tissues. Bull NYU Hosp Jt Dis. 2008;66(3);244-50. PMID 18937640
  20. Roemer FW, Jansen M, Marijnissen ACA, et al. Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort. BMC Musculoskelet Disord. 2022;23(1);988. PMID 36397054
  21. Runhaar J, van Middelkoop M, Oei EHG, et al. Potential surrogate outcomes in individuals at high risk for incident knee osteoarthritis. Osteoarthritis Cartilage. 2023;31(3);414-420. PMID 36646305
  22. Chapple CM, Nicholson H, Baxter GD, et al. Patient characteristics that predict progression of knee osteoarthritis: a systematic review of prognostic studies. Arthritis Care Res (Hoboken). 2011;63(8);1115-25. PMID 21560257
  23. Previtali D, Andriolo L, Di Laura Frattura G, et al. Pain Trajectories in Knee Osteoarthritis-A Systematic Review and Best Evidence Synthesis on Pain Predictors. J Clin Med. 2020;9(9);2828. PMID 32882828
  24. Kelliher A, Beilharz SA, Sutton R. Efficacy of Intra-Articular Corticosteroid Injection for Hip Osteoarthritis: A Systematic Review with Meta-Analysis. J Arthroplasty. 2026;S0883-5403(26)00772-2. PMID 42462884
  25. Mohammadi S, Harandi H, Alikarami S, et al. MRI-defined tissue damage as predictors of the incidence and progression of knee osteoarthritis: A systematic review. Semin Arthritis Rheum. 2026;79;152999. PMID 42176660
  26. Jin X, Antony B, Wang X, et al. Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis. BMJ Open. 2020;10(4);e035302. PMID 32332006
  27. Eseonu KC, Neale J, Lyons A, et al. Are Outcomes of Acute Meniscus Root Tear Repair Better Than Debridement or Nonoperative Management? A Systematic Review. Am J Sports Med. 2022;50(11);3130-3139. PMID 34633226
  28. Siddiq MAB, Duong V, Jia J, et al. Validity of ultrasound in knee osteoarthritis - A systematic review and meta-analysis. Osteoarthritis Cartilage. 2026;34(7);1007-1016. PMID 41831592
  29. Oo WM, Linklater JM, Daniel M, et al. Clinimetrics of ultrasound pathologies in osteoarthritis: systematic literature review and meta-analysis. Osteoarthritis Cartilage. 2018;26(5);601-611. PMID 29426009
  30. Nelson AE, Smith MW, Golightly YM, et al. "Generalized osteoarthritis": a systematic review. Semin Arthritis Rheum. 2014;43(6);713-20. PMID 24461078
  31. Yusuf E, Kortekaas MC, Watt I, et al. Do knee abnormalities visualised on MRI explain knee pain in knee osteoarthritis? A systematic review. Ann Rheum Dis. 2011;70(1);60-67. PMID 20829200
  32. Kraus VB, Burnett B, Coindreau J, et al. Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthritis Cartilage. 2011;19:515-42. PMID 21396468
  33. van Spil WE, DeGroot J, Lems WF, et al. Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying BIPED criteria. Osteoarthritis Cartilage. 2010;18:605-12. PMID 20175979
  34. Peterfy CG, Guermazi A, Zaim S, et al. Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage. 2004;12:177-90. PMID 14972335
  35. Guermazi A, Niu J, Hayashi D, et al. Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis. BMJ. 2012;345:e5339. PMID 22932918
  36. Kraus VB, Collins JE, Hargrove D, et al. Predictive validity of biochemical biomarkers in FNIH OA Biomarkers Consortium. Ann Rheum Dis. 2017;76:186-195. PMID 27296323
  37. Hochberg MC, Guermazi A, Guehring H, et al. Intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness: FORWARD. JAMA. 2019;322:1360-1370. PMID 31593273
  38. Watt FE. Osteoarthritis biomarkers: year in review. Osteoarthritis Cartilage. 2018;26:312-318. PMID 29107060