Journal Logo

Institutional members access full text with Ovid®

Raman Biomarkers Are Associated with Cyclic Fatigue Life of Human Allograft Cortical Bone

Du, Jerry Y. MD1; Flanagan, Christopher D. MD1; Bensusan, Jay S. MS2; Knusel, Konrad D. MS1; Akkus, Ozan PhD1,2; Rimnac, Clare M. PhD1,2

doi: 10.2106/JBJS.18.00832
Scientific Articles
Buy
Supplementary Content
Disclosures

Background: Structural bone allografts are an established treatment method for long-bone structural defects resulting from such conditions as traumatic injury and sarcoma. The functional lifetime of structural allografts depends on resistance to cyclic loading (cyclic fatigue life), which can lead to fracture at stress levels well below the yield strength. Raman spectroscopy biomarkers can be used to non-destructively assess the 3 primary components of bone (collagen, mineral, and water), and may aid in optimizing allograft selection to decrease fatigue fracture risk. We studied the association of Raman biomarkers with the cyclic fatigue life of human allograft cortical bone.

Methods: Twenty-one cortical bone specimens were machined from the femoral diaphyses of 4 human donors (a 63-year old man, a 61-year-old man, a 51-year-old woman, and a 48-year-old woman) obtained from the Musculoskeletal Transplant Foundation. Six Raman biomarkers were analyzed: collagen disorganization, mineral maturation, matrix mineralization, and 3 water compartments. The specimens underwent cyclic fatigue testing under fully reversed conditions (35 and 45 MPa), during which they were tested to fracture or to 30 million cycles (“runout”), simulating 15 years of moderate activity. A tobit censored linear regression model for cyclic fatigue life was created.

Results: The multivariate model explained 60% of the variance in the cyclic fatigue life (R2 = 0.604, p < 0.001). Increases in Raman biomarkers for disordered collagen (coefficient: −2.74×107, p < 0.001) and for loosely collagen-bound water compartments (coefficient: −2.11×108, p < 0.001) were associated with a decreased cyclic fatigue life. Increases in Raman biomarkers for mineral maturation (coefficient: 3.50×108, p < 0.001), matrix mineralization (coefficient: 2.32×106, p < 0.001), tightly collagen-bound water (coefficient: 1.19×108, p < 0.001), and mineral-bound water (coefficient: 3.27×107, p < 0.001) were associated with an increased cyclic fatigue life. Collagen disorder accounted for 44% of the variance in the cyclic fatigue life, mineral maturation accounted for 6%, and all bound water compartments accounted for 3%.

Conclusions: Increasing baseline collagen disorder was associated with a decreased cyclic fatigue life and had the strongest correlation with the cyclic fatigue life of human cortical donor bone. This model should be prospectively validated.

Clinical Relevance: Raman analysis is a promising tool for the non-destructive evaluation of structural bone allograft quality for load-bearing applications.

1Department of Orthopedic Surgery, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio

2Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, Ohio

E-mail address for J.Y. Du: jerry.y.du@gmail.com

Investigation performed at the Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, Ohio

Disclosure: Funding was provided by a grant from the Musculoskeletal Transplant Foundation. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work and “yes” to indicate that the author had a patent and/or copyright, planned, pending, or issued, broadly relevant to this work (Raman Prediction of Bone Quality, which is the subject of this investigation). (http://links.lww.com/JBJS/F351).

Copyright © 2019 by The Journal of Bone and Joint Surgery, Incorporated
You currently do not have access to this article

To access this article: