Improved prediction of femoral fracture toughness in mice by combining standard medical imaging with Raman spectroscopy

Christine Massie; Emma Knapp; Keren Chen; Andrew J Berger; Hani A Awad

doi:10.1016/j.jbiomech.2021.110243

Improved prediction of femoral fracture toughness in mice by combining standard medical imaging with Raman spectroscopy

J Biomech. 2021 Feb 12:116:110243. doi: 10.1016/j.jbiomech.2021.110243. Epub 2021 Jan 13.

Authors

Christine Massie¹, Emma Knapp², Keren Chen³, Andrew J Berger⁴, Hani A Awad⁵

Affiliations

¹ Department of Biomedical Engineering, University of Rochester, 207 Robert B. Goergen Hall, Rochester, NY 14642, USA.
² The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA.
³ The Institute of Optics, University of Rochester, 275 Hutchison Rd., Rochester, NY 14620, USA.
⁴ Department of Biomedical Engineering, University of Rochester, 207 Robert B. Goergen Hall, Rochester, NY 14642, USA; The Institute of Optics, University of Rochester, 275 Hutchison Rd., Rochester, NY 14620, USA.
⁵ Department of Biomedical Engineering, University of Rochester, 207 Robert B. Goergen Hall, Rochester, NY 14642, USA; The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA. Electronic address: hani_awad@urmc.rochester.edu.

Abstract

Bone fragility and fracture risk are assessed by measuring the areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). While aBMD correlates with bone strength, it is a poor predictor of fragility fracture risk. Alternatively, fracture toughness assesses the bone's resistance to crack propagation and fracture, making it a suitable bone quality metric. Here, we explored how femoral midshaft measurements from DXA, micro-computed tomography (µCT), and Raman spectroscopy could predict fracture toughness. We hypothesized that ovariectomy (OVX) decreases aBMD and fracture toughness compared to controls and we can optimize a multivariate assessment of bone quality by combining results from X-ray and Raman spectroscopy. Female mice underwent an OVX (n = 5) or sham (n = 5) surgery at 3 months of age. Femurs were excised 3 months after ovariectomy and assessed with Raman spectroscopy, µCT, and DXA. Subsequently, a notch was created on the anterior side of the mid-diaphysis of the femurs. Three-point bending induced a controlled fracture that initiated at the notch. The OVX mice had a significantly lower aBMD, cortical thickness, and fracture toughness when compared to controls (p < 0.05). A leave one out cross-validated (LOOCV) partial least squares regression (PLSR) model based only on the combination of aBMD and cortical thickness showed no significant predictive correlations with fracture toughness, whereas a PLSR model based on principal components derived from the full Raman spectra yielded significant prediction (r² = 0.71, p < 0.05). Further, the PLSR model was improved by incorporating aBMD, cortical thickness, and principal components from Raman spectra (r² = 0.92, p < 0.001). This exploratory study demonstrates combining X-ray with Raman spectroscopy leads to a more accurate assessment of bone fracture toughness and could be a useful diagnostic tool for the assessment of fragility fracture risk.

Keywords: Computed tomography; DXA; Fracture toughness; Fragility fracture; Osteoporosis; Raman spectroscopy.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Absorptiometry, Photon
Animals
Bone Density
Female
Femoral Fractures* / diagnostic imaging
Humans
Mice
Spectrum Analysis, Raman*
X-Ray Microtomography

Abstract

Publication types

MeSH terms

Grants and funding