Subscribe to RSS
DOI: 10.1055/a-2632-2488
Serum and Urine Biomarkers Can Predict Outcomes after Osteochondral Allograft Transplantation in the Knee
Funding None.

Abstract
Osteochondral allograft transplantation (OCAT) is safe and effective for the treatment of large articular defects in the knee. Yet, there are no quantitative methods for predicting OCAT outcomes. This study was designed to analyze serum and urine biomarkers collected prior to OCAT to determine their capabilities for predicting outcomes with respect to functional graft survival. Prospectively collected data for patients undergoing primary multisurface knee OCAT, enrolled in an outcomes registry, were analyzed for graft survival. Blood and urine samples were collected prior to surgery for biomarker analyses. Biomarker concentrations were analyzed for the capability to predict OCAT failures (revision or arthroplasty) that occurred within the first 2 years. Fifty consecutive patients were included for analysis; the 2-year graft survival (success) rate was 80%. In samples obtained prior to OCAT, concentrations of serum hyaluronan (HA) and urine cross-linked C-telopeptide of type II collagen (CTX-II) were significantly higher for failure patients. A urinary biomarker panel containing cross-linked C-telopeptide of type I collagen (CTX-I), CTX-II, HA, IL-8, MMP-2, MMP-3, MMP-13, osteoprotegrin (OPG), and osteopontin (OPN) was able to predict the likelihood of treatment failure with an area under the curve (AUC) of 0.895, sensitivity of 85.3%, and specificity of 93.8%. Preoperative concentrations of urine CTX-II and urine MMP-3 were significantly associated with a higher risk for OCAT treatment failure. Serum and urine protein biomarkers analyzed prior to surgery have the potential to predict functional graft survival at 2 years following complex multisurface OCAT surgery in the knee. With further validation, these biomarkers may be useful as a component of the shared decision-making process for patients and health care teams to evaluate this treatment option. Level of Evidence 2, prospective cohort study.
Keywords
knee - osteochondral allograft transplantation - biomarkers - shared decision-making process - graft survivalEthical Statement
This study was conducted under approval by the University of Missouri's Institutional Review Board (#2002628).
Publication History
Received: 02 June 2025
Accepted: 10 June 2025
Accepted Manuscript online:
11 June 2025
Article published online:
27 June 2025
© 2025. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Cook JL, Rucinski K, Crecelius C, Fenkell B, Stannard JP. Assessment of outcomes after multisurface osteochondral allograft transplantations in the knee. Orthop J Sports Med 2022; 10 (06) 23 259671221102452
- 2 Cook JL, Rucinski K, Crecelius CR, Stannard JP. Initial outcomes after unicompartmental tibiofemoral bipolar osteochondral and meniscal allograft transplantation in the knee using MOPS-preserved fresh (viable) tissues. Am J Sports Med 2023; 51 (03) 596-604
- 3 Familiari F, Cinque ME, Chahla J. et al. Clinical outcomes and failure rates of osteochondral allograft transplantation in the knee: A systematic review. Am J Sports Med 2018; 46 (14) 3541-3549
- 4 Gross AE, Kim W, Las Heras F, Backstein D, Safir O, Pritzker KPH. Fresh osteochondral allografts for posttraumatic knee defects: long-term followup. Clin Orthop Relat Res 2008; 466 (08) 1863-1870
- 5 Cook JL, Rucinski K, Crecelius CR, Kfuri M, Stannard JP. Treatment failures (revision or arthroplasty) after knee osteochondral allograft transplantation with minimum two-year follow-up. Knee 2024; 46: 128-135
- 6 Kunze KN, Ramkumar PN, Manzi JE, Wright-Chisem J, Nwachukwu BU, Williams III RJ. Risk factors for failure after osteochondral allograft transplantation of the knee: A systematic review and exploratory meta-analysis. Am J Sports Med 2023; 51 (05) 1356-1367
- 7 Rucinski K, Cook JL, Crecelius CR, Stucky R, Stannard JP. Effects of compliance with procedure-specific postoperative rehabilitation protocols on initial outcomes after osteochondral and meniscal allograft transplantation in the knee. Orthop J Sports Med 2019; 7 (11) 2325967119884291
- 8 Luk J, Stoker AM, Teixeiro E. et al. Systematic review of osteochondral allograft transplant immunology: How we can further optimize outcomes. J Knee Surg 2021; 34 (01) 30-38
- 9 Ewing MA, Stoker AM, Leary EV. et al. Treatment-monitoring capabilities of serum and urine biomarkers for meniscal allograft transplantation in a preclinical canine model. Am J Sports Med 2022; 50 (10) 2714-2721
- 10 Kraus VB, Collins JE, Hargrove D. et al.; OA Biomarkers Consortium. Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium. Ann Rheum Dis 2017; 76 (01) 186-195
- 11 Goode AP, Marshall SW, Kraus VB. et al. Association between serum and urine biomarkers and lumbar spine individual radiographic features: the Johnston County Osteoarthritis Project. Osteoarthritis Cartilage 2012; 20 (11) 1286-1293
- 12 Wolfe PN, Stoker AM, Leary E, Crist BD, Bozynski CC, Cook JL. Evaluation of serum and urine biomarker panels for developmental dysplasia of the hip prior to onset of secondary osteoarthritis. Cartilage 2024; 15 (02) 164-174
- 13 Kalogera S, Jansen MP, Bay-Jensen AC. et al. Relevance of biomarkers in serum vs. synovial fluid in patients with knee osteoarthritis. Int J Mol Sci 2023; 24 (11) 9483
- 14 Lineham B, Altaie A, Harwood P, McGonagle D, Pandit H, Jones E. A systematic review on the potential value of synovial fluid biomarkers to predict clinical outcomes in cartilage repair treatments. Osteoarthritis Cartilage 2022; 30 (08) 1035-1049
- 15 Werner NC, Stoker AM, Bozynski CC, Keeney JA, Cook JL. Characterizing correlations among disease severity measures in osteochondral tissues from osteoarthritic knees. J Orthop Res 2021; 39 (05) 1103-1112
- 16 Roller BL, Monibi F, Stoker AM, Bal BS, Cook JL. Identification of novel synovial fluid biomarkers associated with meniscal pathology. J Knee Surg 2016; 29 (01) 47-62
- 17 Monibi F, Roller BL, Stoker A, Garner B, Bal S, Cook JL. Identification of synovial fluid biomarkers for knee osteoarthritis and correlation with radiographic assessment. J Knee Surg 2016; 29 (03) 242-247
- 18 Cook JL, Stoker AM, Stannard JP. et al. A novel system improves preservation of osteochondral allografts. Clin Orthop Relat Res 2014; 472 (11) 3404-3414
- 19 Stoker AM, Stannard JP, Cook JL. Chondrocyte viability at time of transplantation for osteochondral allografts preserved by the Missouri Osteochondral Preservation System versus standard tissue bank protocol. J Knee Surg 2018; 31 (08) 772-780
- 20 Oladeji LO, Stannard JP, Cook CR. et al. Effects of autogenous bone marrow aspirate concentrate on radiographic integration of femoral condylar osteochondral allografts. Am J Sports Med 2017; 45 (12) 2797-2803
- 21 Stannard JP, Cook JL. Prospective assessment of outcomes after primary unipolar, multisurface, and bipolar osteochondral allograft transplantations in the knee: A comparison of 2 preservation methods. Am J Sports Med 2020; 48 (06) 1356-1364
- 22 Schreiner AJ, Stannard JP, Cook CR. et al. Initial clinical outcomes comparing frozen versus fresh meniscus allograft transplants. Knee 2020; 27 (06) 1811-1820
- 23 Zitsch BP, Stannard JP, Worley JR, Cook JL, Leary EV. Patient-reported outcomes for large bipolar osteochondral allograft transplantation in combination with realignment osteotomies for the knee. J Knee Surg 2021; 34 (11) 1260-1266
- 24 Buyuk AF, Stannard JP, Rucinski K, Crecelius CR, Cook JL. The Missouri Osteochondral Preservation System is associated with better short-term outcomes than standard preservation methods when performing osteochondral allograft transplantation using shell grafts for patellofemoral lesions. Arthroscopy 2023; 39 (03) 650-659
- 25 Rucinski K, Stucky R, Crecelius CR, Stannard JP, Cook JL. Effects of patient assessment and education by an integrated care team on postoperative adherence and failure rates after osteochondral allograft and meniscal allograft transplantation in the knee. Orthop J Sports Med 2023; 11 (05) 23 259671231160780
- 26 Boonstra AM, Schiphorst Preuper HR, Reneman MF, Posthumus JB, Stewart RE. Reliability and validity of the visual analogue scale for disability in patients with chronic musculoskeletal pain. Int J Rehabil Res 2008; 31 (02) 165-169
- 27 Martin RL, Kivlan BR, Christoforetti JJ. et al. Minimal clinically important difference and substantial clinical benefit values for a pain visual analog scale after hip arthroscopy. Arthroscopy 2019; 35 (07) 2064-2069
- 28 Higgins LD, Taylor MK, Park D. et al.; International Knee Documentation Committee. Reliability and validity of the International Knee Documentation Committee (IKDC) Subjective Knee Form. Joint Bone Spine 2007; 74 (06) 594-599
- 29 O'Connor CM, Ring D. Correlation of Single Assessment Numeric Evaluation (SANE) with other patient reported outcome measures (PROMs). Arch Bone Jt Surg 2019; 7 (04) 303-306
- 30 Christensen J, Peters C, Gililland J, Stoddard G, Pelt C. Physical activity, pain interference and comorbidities relate to PROMIS physical function in younger adults following total knee arthroplasty. Disabil Rehabil 2021; 43 (26) 3741-3747
- 31 Hays RD, Schalet BD, Spritzer KL, Cella D. Two-item PROMIS® global physical and mental health scales. J Patient Rep Outcomes 2017; 1 (01) 2
- 32 Coppelman EB, David FH, Tóth F, Ernst NS, Trumble TN. The association between collagen and bone biomarkers and radiographic osteoarthritis in the distal tarsal joints of horses. Equine Vet J 2020; 52 (03) 391-398
- 33 Hurvich CM, Simonoff JS, Tsai CL. Smoothing parameter selection in nonparametric regression using an improved Akaike Information Criterion. J R Stat Soc B 1998; 60: 271-293
- 34 Palà E, Bustamante A, Pagola J. et al. Blood-based biomarkers to search for atrial fibrillation in high-risk asymptomatic individuals and cryptogenic stroke patients. Front Cardiovasc Med 2022; 9: 908053
- 35 Burland JP, Hunt ER, Lattermann C. Serum biomarkers in healthy, injured, and osteoarthritic knees: A critical review. J Cartil Jt Preserv 2023; 3 (02) 100091
- 36 Herrero-Manley L, Alabajos-Cea A, Suso-Martí L. et al. Serum lipid biomarkers and inflammatory cytokines associated with onset and clinical status of patients with early knee osteoarthritis. Front Nutr 2023; 10: 1126796
- 37 Kwan Tat S, Lajeunesse D, Pelletier JP, Martel-Pelletier J. Targeting subchondral bone for treating osteoarthritis: what is the evidence?. Best Pract Res Clin Rheumatol 2010; 24 (01) 51-70
- 38 Hardy E, Fernandez-Patron C. Destroy to rebuild: The connection between bone tissue remodeling and matrix metalloproteinases. Front Physiol 2020; 11: 47
- 39 Braaten JA, Banovetz MT, DePhillipo NN. et al. Biomarkers for osteoarthritis diseases. Life (Basel) 2022; 12 (11) 1799
- 40 Henrotin Y, Sanchez C, Bay-Jensen AC, Mobasheri A. Osteoarthritis biomarkers derived from cartilage extracellular matrix: Current status and future perspectives. Ann Phys Rehabil Med 2016; 59 (03) 145-148
- 41 De Roover A, Escribano-Núñez A, Monteagudo S, Lories R. Fundamentals of osteoarthritis: Inflammatory mediators in osteoarthritis. Osteoarthritis Cartilage 2023; 31 (10) 1303-1311
- 42 Ruan G, Xu J, Wang K. et al. Associations between serum IL-8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis. Clin Rheumatol 2019; 38 (12) 3609-3617
- 43 Leong DJ, Hardin JA, Cobelli NJ, Sun HB. Mechanotransduction and cartilage integrity. Ann N Y Acad Sci 2011; 1240: 32-37
- 44 Wolfe PN, Stoker AM, Crist BD, Leary E, Bozynski CC, Cook JL. Evaluation of mechanistic serum and urine biomarkers for secondary osteoarthritis associated with developmental dysplasia of the hip. J Orthop 2023; 42: 24-29
- 45 Rucinski K, Leary E, Royse LA. Factors important to patients when making treatment decisions for knee osteoarthritis. J Knee Surg 2023; 36 (14) 1413-1421