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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.

SUBMITTER: Boskey AL

PROVIDER: S-EPMC4862946 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Examining the Relationships Between Bone Tissue Composition, Compositional Heterogeneity, and Fragility Fracture: A Matched Case-Controlled FTIRI Study.

Boskey Adele L AL Donnelly Eve E Boskey Elizabeth E Spevak Lyudmila L Ma Yan Y Zhang Wei W Lappe Joan J Recker Robert R RR

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20151224 5

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 ...[more]

PMID: 26636271

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Project description:BackgroundRecent studies are lacking reports on mortality after non-hip fractures in adults aged >?65.MethodsThis retrospective, matched-cohort study used de-identified health services data from the publicly funded healthcare system in Ontario, Canada, contained in the ICES Data Repository. Patients aged 66?years and older with an index fragility fracture occurring at any osteoporotic site between 2011 and 2015 were identified from acute hospital admissions, emergency and ambulatory care using International Classification of Diseases (ICD)-10 codes and data were analyzed until 2017. Thus, follow-up ranged from 2?years to 6?years. Patients were excluded if they presented with an index fracture occurring at a non-osteoporotic fracture site, their index fracture was associated with a trauma code, or they experienced a previous fracture within 5?years prior to their index fracture. This fracture cohort was matched 1:1 to controls within a non-fracture cohort by date, sex, age, geography and comorbidities. All-cause mortality risk was assessed.ResultsThe survival probability for up to 6?years post-fracture was significantly reduced for the fracture cohort vs matched non-fracture controls (p <?0.0001; n =?101,773 per cohort), with the sharpest decline occurring within the first-year post-fracture. Crude relative risk of mortality (95% confidence interval) within 1-year post-fracture was 2.47 (2.38-2.56) in women and 3.22 (3.06-3.40) in men. In the fracture vs non-fracture cohort, the absolute mortality risk within one year after a fragility fracture occurring at any site was 12.5% vs 5.1% in women and 19.5% vs 6.0% in men. The absolute mortality risk within one year after a fragility fracture occurring at a non-hip vs hip site was 9.4% vs 21.5% in women and 14.4% vs 32.3% in men.ConclusionsIn this real-world cohort aged >?65?years, a fragility fracture occurring at any site was associated with reduced survival for up to 6?years post-fracture. The greatest reduction in survival occurred within the first-year post-fracture, where mortality risk more than doubled and deaths were observed in 1 in 11 women and 1 in 7 men following a non-hip fracture and in 1 in 5 women and 1 in 3 men following a hip fracture.

Project description:Background and objectivesTrabecular bone score is a gray-level textural measure obtained from dual energy x-ray absorptiometry lumbar spine images that provides information independent of areal bone mineral density. The association between trabecular bone score and incident fractures in adults with reduced kidney function and whether this association differs from that of adults with normal kidney function are unknown.Design, setting, participants, & measurementsWe included 1426 participants ages ?40 years old (mean age of 67 years) in the community-based Canadian Multicentre Osteoporosis Study. We stratified participants at cohort entry (2005-2008) by eGFR (eGFR<60 ml/min per 1.73 m2 [n=199; 72.4% stage 3a, 25.1% stage 3b, and 2.5% stage 4] versus ?60 ml/min per 1.73 m2 [n=1227]). Trabecular bone score was obtained from lumbar spine (L1-L4) dual energy x-ray absorptiometry images, with a lower trabecular bone score representing worse bone structure. Over an average of 4.7 years follow-up (maximum follow-up of 5 years), we documented incident fragility (low-trauma) fracture events (excluding craniofacial, foot, and hand sites). We used a modified Kaplan-Meier estimator to determine the 5-year probability of fracture. Cox proportional hazard regression per SD lower trabecular bone score expressed the gradient of fracture risk.ResultsIndividuals with an eGFR<60 ml/min per 1.73 m2 who had a trabecular bone score value below the median (<1.277) had a significantly higher 5-year fracture probability than those above the median (18.1% versus 6.2%; P=0.01). The association between trabecular bone score and fracture was independent of bone mineral density and other clinical risk factors in adults with reduced and normal kidney function (adjusted hazard ratio per SD lower trabecular bone score: eGFR<60 ml/min per 1.73 m2: adjusted hazard ratio, 1.62; 95% confidence interval, 1.04 to 2.51; eGFR?60 ml/min per 1.73 m2: adjusted hazard ratio, 1.44; 95% confidence interval, 1.13 to 1.83).ConclusionsLower lumbar spine trabecular bone score is independently associated with a higher fracture risk in adults with reduced kidney function. Additional study is needed to examine the association between trabecular bone score and fractures in individuals with diagnosed CKD-mineral and bone disorder.

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Dataset Information

Examining the Relationships Between Bone Tissue Composition, Compositional Heterogeneity, and Fragility Fracture: A Matched Case-Controlled FTIRI Study.

Publications

Examining the Relationships Between Bone Tissue Composition, Compositional Heterogeneity, and Fragility Fracture: A Matched Case-Controlled FTIRI Study.

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