Collagen X Longitudinal Fracture Biomarker Suggests Staged Fixation in Tibial Plateau Fractures Delays Rate of Endochondral Repair.

Objectives: To use a novel, validated bioassay to monitor serum concentrations of a breakdown product of collagen X in a prospective longitudinal study of patients sustaining isolated tibial plateau fractures. Collagen X is the hallmark extracellular matrix protein present during conversion of soft, cartilaginous callus to bone during endochondral repair. Previous preclinical and clinical studies demonstrated a distinct peak in collagen X biomarker (CXM) bioassay levels after long bone fractures.
Setting: Level 1 academic trauma facility.
Patients/participants: Thirty-six patients; isolated tibial plateau fractures.
Intervention: (3) Closed treatment, ex-fix (temporizing/definitive), and open reduction internal fixation.
Main Outcome Measurements: Collagen X serum biomarker levels (CXM bioassay).
Results: Twenty-two men and 14 women (average age: 46.3 y; 22.6-73.4, SD 13.3) enrolled (16 unicondylar and 20 bicondylar fractures). Twenty-five patients (72.2%) were treated operatively, including 12 (33.3%) provisionally or definitively treated by ex-fix. No difference was found in peak CXM values between sexes or age. Patients demonstrated peak expression near 1000 pg/mL (average: male-986.5 pg/mL, SD 369; female-953.2 pg/mL, SD 576). There was no difference in peak CXM by treatment protocol, external fixator use, or fracture severity (Schatzker). Patients treated with external fixation (P = 0.05) or staged open reduction internal fixation (P = 0.046) critically demonstrated delayed peaks.
Conclusions: Pilot analysis demonstrates a strong CXM peak after fractures commensurate with previous preclinical and clinical studies, which was delayed with staged fixation. This may represent the consequence of delayed construct loading. Further validation requires larger cohorts and long-term follow-up. Collagen X may provide an opportunity to support prospective interventional studies testing novel orthobiologics or fixation techniques.
Level of Evidence: Level II, prospective clinical observational study.
Competing Interests: C. S Bahney discloses an unpaid position on the Board of Directors for Orthopaedic Research Society (ORS), Tissue Engineering and Regenerative Medicine International Society (TERMIS), and the International Section of Fracture Repair (ISFR). Furthermore, C. S. Bahney is a paid employee of the nonprofit Steadman Philippon Research Institute (SPRI). SPRI exercises special care to identify any financial interests or relationships related to research conducted here. During the past calendar year, SPRI has received grant funding or in-kind donations from Arthrex, DJO, MLB, Ossur, Siemens, Smith & Nephew, XTRE, and philanthropy. These funding sources provided no support for the work presented in this manuscript. T. Miclau discloses board or committee positions for the AO Foundation, Inman Abbott Society, International Combined Orthopaedic Research Societies, International Orthopaedic Trauma Association, Orthopaedic Research Society, Orthopaedic Trauma Association, Osteosynthesis and Trauma Care Foundation, and San Francisco General Hospital Foundation. He has received research support from Baxter and is a paid consultant for Arquos, Bone Therapeutics, NXTSENS, Surrozen, and Synthes with stock or stock options at Arquos. None of the paid positions are related to the work presented in this manuscript. R. Coughlan reports patent rights to the CXM biomarker assay technology and a portion of royalties generated through its licensure. He is a paid consultant to Therachon AG and BioMarin Pharmaceutical. None of the paid positions are related to the work presented in this manuscript. The other authors report no conflict of interest.
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