Use of FTIR Spectroscopic Imaging to Identify Parameters Associated With Fragility Fracture

BMD does not entirely explain an individual's risk of fracture. The purpose of this study was to assess whether specific differences in spatially resolved bone composition also contribute to fracture risk. These differences were assessed using Fourier transform infrared spectroscopic imaging (FTIRI) and analyzed through multiple logistic regression. Models were constructed to determine whether FTIRI measured parameters describing mineral content, mineral crystal size and perfection, and collagen maturity were associated with fracture. Cortical and cancellous bone were independently evaluated in iliac crest biopsies from 54 women (32 with fractures, 22 without) who had significantly different spine but not hip BMDs and ranged in age from 30 to 83 yr. The parameters that were significantly associated with fracture in the model were cortical and cancellous collagen maturity (increased with increased fracture risk), cortical mineral/matrix ratio (higher with increased fracture risk), and cancellous crystallinity (increased with increased fracture risk). As expected, because of its correlation with cortical but not cancellous bone density, hip BMD was significantly associated with fracture risk in the cortical but not the cancellous model. This research suggests that additional parameters associated with fracture risk should be targeted for therapies for osteoporosis.

[1]  S A Goldstein,et al.  Biomechanics of Fracture: Is Bone Mineral Density Sufficient to Assess Risk? , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[2]  M. Karsdal,et al.  The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality , 2008, Osteoporosis International.

[3]  J. Jeffery,et al.  Age-related changes in the orientation and particle size of the mineral phase in human femoral cortical bone , 2006, Calcified Tissue International.

[4]  William F. Finney,et al.  Bone tissue compositional differences in women with and without osteoporotic fracture. , 2006, Bone.

[5]  M. Saito,et al.  Collagen maturity, glycation induced-pentosidine, and mineralization are increased following 3-year treatment with incadronate in dogs , 2008, Osteoporosis International.

[6]  O Johnell,et al.  Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. , 1996, BMJ.

[7]  D. Reid,et al.  Predicting a second hip fracture. , 1999, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[8]  B. Riggs,et al.  Colles' fracture and subsequent hip fracture risk. , 1982, Clinical orthopaedics and related research.

[9]  L Klenerman,et al.  Changes in crystal size and orientation of acidic glycosaminoglycans at the fracture site in fractured necks of femur. , 1983, The Journal of bone and joint surgery. British volume.

[10]  Timothy M. Wright,et al.  Abnormal Mineral-Matrix Interactions Are a Significant Contributor to Fragility in oim/oim Bone , 2007, Calcified Tissue International.

[11]  A. Tenenhouse,et al.  Association Between Change in BMD and Fragility Fracture in Women and Men , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[12]  A. Boskey,et al.  FTIR Microspectroscopic Analysis of Human Iliac Crest Biopsies from Untreated Osteoporotic Bone , 1997, Calcified Tissue International.

[13]  C. Benhamou.  Effects of osteoporosis medications on bone quality. , 2007, Joint, bone, spine : revue du rhumatisme.

[14]  E. Barrett-Connor,et al.  Predictive Value of Low BMD for 1‐Year Fracture Outcomes Is Similar for Postmenopausal Women Ages 50‐64 and 65 and Older: Results From the National Osteoporosis Risk Assessment (NORA) , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  M Viceconti,et al.  Dependence of mechanical compressive strength on local variations in microarchitecture in cancellous bone of proximal human femur. , 2008, Journal of biomechanics.

[16]  O. Akkus,et al.  The associations between mineral crystallinity and the mechanical properties of human cortical bone. , 2008, Bone.

[17]  Matthew J. Silva,et al.  Decreased Collagen Organization and Content Are Associated With Reduced Strength of Demineralized and Intact Bone in the SAMP6 Mouse , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  D. Burr,et al.  Chemical makeup of microdamaged bone differs from undamaged bone. , 2006, Bone.

[19]  M. Chance,et al.  In situ chemistry of osteoporosis revealed by synchrotron infrared microspectroscopy. , 2003, Bone.

[20]  P. West,et al.  Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation , 2005, Osteoporosis International.

[21]  A. Boskey,et al.  Spatial Variation in Osteonal Bone Properties Relative to Tissue and Animal Age , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  Paul Roschger,et al.  Bone quality determined by Fourier transform infrared imaging analysis in mild primary hyperparathyroidism. , 2008, The Journal of clinical endocrinology and metabolism.

[23]  Kay Dickersin,et al.  Osteoporosis prevention, diagnosis, and therapy. , 2000, NIH consensus statement.

[24]  S. Majumdar,et al.  High-resolution magnetic resonance imaging: three-dimensional trabecular bone architecture and biomechanical properties. , 1998, Bone.

[25]  A. Boskey,et al.  Bone Fragility and Collagen Cross‐Links , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[26]  M. Karsdal,et al.  Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies , 2008, Osteoporosis International.

[27]  A. Boskey,et al.  Spectroscopic markers of bone quality in alendronate-treated postmenopausal women , 2009, Osteoporosis International.

[28]  M. Kassem,et al.  Effect of Hormone Replacement Therapy on Bone Quality in Early Postmenopausal Women , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  C. Benhamou,et al.  Devising global strategies for fracture-risk evaluation. , 2007, Joint, bone, spine : revue du rhumatisme.

[30]  M. Saito,et al.  Degree of Mineralization-related Collagen Crosslinking in the Femoral Neck Cancellous Bone in Cases of Hip Fracture and Controls , 2006, Calcified Tissue International.

[31]  Richard Mendelsohn,et al.  Infrared analysis of bone in health and disease. , 2005, Journal of biomedical optics.

[32]  R O Ritchie,et al.  Deep-ultraviolet Raman spectroscopy study of the effect of aging on human cortical bone. , 2005, Journal of biomedical optics.

[33]  A. Bailey,et al.  Differences in composition of avian bone collagen following genetic selection for resistance to osteoporosis , 2002, British poultry science.

[34]  M. Chance,et al.  In situ analysis of mineral content and crystallinity in bone using infrared micro-spectroscopy of the nu(4) PO(4)(3-) vibration. , 2001, Biochimica et biophysica acta.

[35]  S. Cummings,et al.  Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women: the study of osteoporotic fractures. , 2007, Archives of internal medicine.

[36]  A. Boskey,et al.  Genetic Collagen Diseases: Influence of Collagen Mutationson Structure and Mechanical Behavior , 2008 .

[37]  A. Boskey,et al.  Fourier Transform Infrared Imaging Microspectroscopy and Tissue-Level Mechanical Testing Reveal Intraspecies Variation in Mouse Bone Mineral and Matrix Composition , 2008, Calcified Tissue International.

[38]  W. Lu,et al.  Chemical composition, crystal size and lattice structural changes after incorporation of strontium into biomimetic apatite. , 2007, Biomaterials.

[39]  R M Aspden,et al.  A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. , 2001, The Journal of clinical investigation.

[40]  I. Bajnóczky,et al.  Analysis of pathological and non-pathological human skeletal remains by FT-IR spectroscopy. , 2008, Forensic science international.

[41]  Susan R. Johnson,et al.  Osteoporosis prevention, diagnosis, and therapy. , 2001, JAMA.