Bisphosphonates are the most widely prescribed pharmacologic treatment for
osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone. The objective of this study was to compare the compositional and mechanical properties of bone biopsies from bisphosphonate-treated patients with AFFs to those from patients with typical osteoporotic fractures with and without bisphosphonate treatment. Biopsies of proximal femoral cortical bone adjacent to the fracture site were obtained from postmenopausal women during fracture repair surgery (fracture groups, n= 33) or total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment [+BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7 (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; −BIS Typical: n = 11; −BIS Nonfx: n = 12]. Vibrational spectroscopy and nanoindentation showed that tissue from bisphosphonate-treated women with atypical fractures was harder and more mineralized than that from bisphosphonate-treated women with typical osteoporotic fractures. In addition, fracture mechanics measurements showed that tissue from patients treated with bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-naïve patients. Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates.
Pablo Palomino will present his poster entitled, “Advanced glycation endproducts impair cortical bone tissue quality in men with type 2 diabetes mellitus.” Erik Taylor will present his power entitled, “Raman and FTIR bone mineral crystallinity and carbonate content correlate with physical chemical measures.” Ashley Lloyd will present her poster entitled, “Multiscale characterization of material properties of cortical tissue from patients with atypical femoral fractures.”
PhD student Heather Hunt was awarded a young investigator award at the International Conference on the Chemistry and Biology of Mineralized Tissues in Potsdam, Germany to present her abstract entitled, “Collagen matrix alterations lead to bone embrittlement in type 2 diabetic men.”
Raman and Fourier transform infrared (FT-IR) spectroscopic imaging techniques can be used to characterize bone composition. In this study, our objective was to validate the Raman mineral:matrix ratios (ν1 PO4:amide III, ν1 PO4:amide I, ν PO4:Proline + hydroxyproline, ν1 PO4:Phenylalanine, ν1 PO4:δ CH2 peak area ratios) by correlating them to ash fraction and the IR mineral:matrix ratio (ν3 PO4:amide I peak area ratio) in chemical standards and native bone tissue. Chemical standards consisting of varying ratios of synthetic hydroxyapatite (HA) and collagen, as well as bone tissue from humans, sheep, and mice, were characterized with confocal Raman spectroscopy and FT-IR spectroscopy and gravimetric analysis. Raman and IR mineral:matrix ratio values from chemical standards increased reciprocally with ash fraction (Raman ν1 PO4/
Amide III: P < 0.01, R2 = 0.966; Raman ν1 PO4/Amide I: P < 0.01, R2 = 0.919; Raman ν1 PO4/Proline + Hydroxyproline: P < 0.01, R2 = 0.976; Raman ν1 PO4/Phenylalanine: P < 0.01, R2 = 0.911; Raman ν1 PO4/δ CH2: P < 0.01, R2 = 0.894; IR P < 0.01, R2 = 0.91). Fourier transform infrared mineral:matrix ratio values from native bone tissue were also similar to theoretical mineral:matrix ratio values for a given ash fraction. Raman and IR mineral:matrix ratio values were strongly correlated (P < 0.01, R2 = 0.82). These results were confirmed by calculating the mineral:matrix ratio for theoretical IR spectra, developed by applying the Beer–Lambert law to calculate the relative extinction coefficients of HA and collagen over the same range of wavenumbers (800–1800 cm–1). The results confirm that the Raman mineral:matrix bone composition parameter correlates strongly to ash fraction and to its IR counterpart. Finally, the mineral:matrix ratio values of the native bone tissue are similar to those of both chemical standards and theoretical values, confirming the biological relevance of the chemical standards and the characterization techniques.
Pablo Palomino will present a podium talk entitled, “Cancellous And Cortical Bone Tissue Quality In Men Are Differentially Affected By Type 2 Diabetes Mellitus.”
Undergraduates Louis DeLucia and Sarah Burke will present a poster entitled, “The Effect of Type 2 Diabetes on the Mechanical and Compositional Properties of Cortical Bone in Men.”
Erik Taylor will present a poster entitled, “Raman and FTIR bone quality parameters correlate with physical chemical properties of chemical standards and native tissue.”