title: Examining the Relationships Between Bone Tissue Composition, Compositional Heterogeneity, and Fragility Fracture: A Matched Case-Controlled FTIRI Study.
abstract: Fourier transform infrared imaging (FTIRI) provides information on spatial distribution of the chemical composition of thin tissue specimens at ∼7 µm spatial resolution. This study of 120 age- and bone mineral density (BMD)-matched patients was designed to investigate the association of FTIRI variables, measured in iliac crest biopsies, with fragility fractures at any site. An earlier study of 54 women found hip BMD to be a significant explanatory variable of fracture risk for cortical bone but not for cancellous bone. In the current study, where age and BMD were controlled through matching, no such association was observed, validating the pairing scheme. Our first study of unmatched iliac crest biopsies found increases in collagen maturity (cancellous and cortical bone) and mineral crystal size (cortical bone only) to be a significant explanatory variable of fracture when combined with other covariates. The ratio for collagen maturity has been correlated to the amount of enzymatic collagen cross-links. To assess the impact of other FTIRI variables (acid phosphate substitution, carbonate-to-phosphate ratio, and the pixel distribution [heterogeneity] of all relevant FTIRI variables), we examined biopsies from a matched case-controlled study, in which 60 women with fractures were each paired with an age- and BMD-matched female control. With the matched data set of 120 women, conditional logistic regression analyses revealed that significant explanatory variables of fracture were decreased carbonate-to-phosphate ratio in both cancellous (odds ratio [OR] = 0.580, 95% confidence interval [CI] 0.37-0.909, p = 0.0176) and cortical bone (OR = 0.519, 95% CI 0.325-0.829, p = 0.0061), and increased heterogeneity (broadened pixel distribution) of collagen maturity for cancellous bone (OR = 1.549, 95% CI 1.002-2.396, p = 0.0491). The observation that collagen maturity was no longer linked to fracture in age- and BMD-matched samples suggests that age-dependent variation in collagen maturity may be a more important contributory factor to fragility fractures than previously thought. © 2015 American Society for Bone and Mineral Research.
authors.affiliation: Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY, USA.
authors.forename: Adele L
authors.initials: AL
authors.lastname: Boskey
authors.affiliation: Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY, USA.|Materials Science and Engineering Department, Cornell University, Ithaca, NY, USA.
authors.forename: Eve
authors.initials: E
authors.lastname: Donnelly
authors.affiliation: Women's and Gender Studies, Boston University, Boston, MA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Boskey
authors.affiliation: Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY, USA.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Spevak
authors.affiliation: Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Osteoporosis Research Center, Creighton University, Omaha, NE, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Lappe
authors.affiliation: Osteoporosis Research Center, Creighton University, Omaha, NE, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
mesh_terms: D000368:Aged; D015519:Bone Density; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism; D005260:Female; D006620:Hip Fractures / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007085:Ilium / Q000000981:diagnostic imaging / Q000378:metabolism; D008875:Middle Aged; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D003094:Collagen
keywords: AGING; ANALYSIS/QUANTITATION OF BONE; FRACTURE RISK; FTIR IMAGING; OSTEOPOROSIS