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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.

Project description:Fractures associated with bone fragility in older adults signal the potential for secondary fracture. Fragility fractures often precipitate further decline in health and loss of mobility, with high associated costs for patients, families, society and the healthcare system. Promptly initiating a coordinated, comprehensive pharmacological bone health and falls prevention program post-fracture may improve osteoporosis treatment compliance; and reduce rates of falls and secondary fractures, and associated morbidity, mortality and costs.This pragmatic, controlled trial at 11 hospital sites in eight regions in Quebec, Canada, will recruit community-dwelling patients over age 50 who have sustained a fragility fracture to an intervention coordinated program or to standard care, according to the site. Site study coordinators will identify and recruit 1,596 participants for each study arm. Coordinators at intervention sites will facilitate continuity of care for bone health, and arrange fall prevention programs including physical exercise. The intervention teams include medical bone specialists, primary care physicians, pharmacists, nurses, rehabilitation clinicians, and community program organizers.The primary outcome of this study is the incidence of secondary fragility fractures within an 18-month follow-up period. Secondary outcomes include initiation and compliance with bone health medication; time to first fall and number of clinically significant falls; fall-related hospitalization and mortality; physical activity; quality of life; fragility fracture-related costs; admission to a long term care facility; participants' perceptions of care integration, expectations and satisfaction with the program; and participants' compliance with the fall prevention program. Finally, professionals at intervention sites will participate in focus groups to identify barriers and facilitating factors for the integrated fragility fracture prevention program.This integrated program will facilitate knowledge translation and dissemination via the following: involvement of various collaborators during the development and set-up of the integrated program; distribution of pamphlets about osteoporosis and fall prevention strategies to primary care physicians in the intervention group and patients in the control group; participation in evaluation activities; and eventual dissemination of study results.

Project description:Our aim was to evaluate the gap in osteoporosis treatment and the impact of osteoporosis treatment on subsequent fragility fractures. We found osteoporosis medication use lowered risk of subsequent fractures by 21% and that black race, higher CCI scores, dementia, and kidney diseases reduced the likelihood of osteoporosis medication use. INTRODUCTION:The goal of this study was to evaluate the predictors of osteoporosis medication use and compare the risk of fragility fractures within 1 year of a fragility fracture between osteoporosis treated and untreated women. METHODS:We conducted a retrospective, observational cohort study using the national Medicare database. Elderly women (≥65 years) who were hospitalized or had an outpatient/ER service for fragility fracture between January 1, 2011 and December 31, 2011 were included. The outcomes of interest were the correlates of and time-to-osteoporosis medication use and risk of a subsequent fracture within 12 months for treated and untreated women. Cox regression was used to evaluate the predictors of treatment use and the risk of fracture based on treatment status. RESULTS:Women (28,722) (27.7%) were treated with osteoporosis medication within 12 months of index fracture, and 74,979 (72.2%) were untreated. A number of patient characteristics were associated with a reduced likelihood of osteoporosis medication use, including black race, higher Charlson comorbidity index scores, presence of dementia, and kidney diseases in the baseline. The predictor most strongly and positively associated with osteoporosis medication use after fracture was osteoporosis medication use before fragility fracture (HR = 7.87; 95% CI 7.67-8.07). After adjusting for baseline characteristics, osteoporosis medication use lowered the risk of subsequent fractures by 21% (HR = 0.79, 95% CI 0.75-0.83) over 12 months compared to women without treatment. CONCLUSIONS:Demographics and clinical characteristics were strong predictors of osteoporosis medication use. In the US Medicare population, osteoporosis treatment significantly reduced the risk of fragility fractures.

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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