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Nishiyama K.K.,Columbia University | Nishiyama K.K.,McCaig Institute for Bone and Joint Health | Ito M.,Nagasaki University | Harada A.,National Center for Geriatrics and Gerontology | And 2 more authors.
Osteoporosis International

Summary: We used quantitative computed tomography and finite element analysis to classify women with and without hip fracture. Highly accurate classifications were achieved indicating the potential for these methods to be used for subject-specific assessment of fracture risk. Introduction: Areal bone mineral density (aBMD) is the current clinical diagnostic standard for assessing fracture risk; however, many fractures occur in people not defined as osteoporotic by aBMD. Finite element (FE) analysis based on quantitative computed tomography (QCT) images takes into account both bone material and structural properties to provide subject-specific estimates of bone strength. Thus, our objective was to determine if FE estimates of bone strength could classify women with and without hip fracture. Methods: Twenty women with femoral neck fracture and 15 women with trochanteric fractures along with 35 age-matched controls were scanned with QCT at the hip. Since it is unknown how a specific subject will fall, FE analysis was used to estimate bone stiffness and bone failure load under loading configurations with femoral neck internal rotation angles ranging from -30° to 45° with 15° intervals. Support vector machine (SVM) models and a tenfold cross-validation scheme were used to classify the subjects with and without fracture. Results: High accuracy was achieved when using only FE analysis for classifying the women with and without fracture both when the fracture types were pooled (82.9%) and when analyzed separately by femoral neck fracture (87.5%) and trochanteric fracture (80.0%). The accuracy was further increased when FE analysis was combined with volumetric BMD (pooled fractures accuracy, 91.4%) Conclusions: While larger prospective studies are needed, these results demonstrate that FE analysis using multiple loading configurations together with SVM models can accurately classify individuals with previous hip fracture. © International Osteoporosis Foundation and National Osteoporosis Foundation 2013. Source

Kos O.,University of Toronto | Hughson R.L.,University of Waterloo | Hart D.A.,McCaig Institute for Bone and Joint Health | Clement G.,International Space University | And 8 more authors.

CD200 is a transmembrane protein that belongs to the immunoglobulin family of proteins and is ubiquitously expressed on a variety of cell types. Upon interaction with its receptors (CD200Rs) expressed on myeloid-derived cells and T lymphocytes, an immunoregulatory signal is delivered to receptor-expressing cells. Previous studies have implicated a role for CD200:CD200R in the regulation of the expression of mRNA markers of osteoclastogenesis/osteoblastogenesis, following interaction of CD200 (on osteoblast precursors) with CD200R1 (on osteoclast precursors). Signaling of CD200R1 is hypothesized to attenuate osteoclastogenesis. We have investigated whether levels of soluble forms of CD200 and/or CD200R1 (sCD200, sCD200R1) are altered in volunteers undergoing 6° head down tilt bed rest to mimic conditions of microgravity known to be associated with preferential osteoclastogenesis and whether countermeasures, reported to be beneficial in attenuation of bone loss under microgravity conditions, would lead to altered sCD200 and sCD200R1 levels. Our data suggest that, as predicted, sCD200 levels fall under bed rest conditions while sCD200R1 levels rise. In subjects undergoing 30-minute per day continuous centrifugation protocols, as a countermeasure to attenuate changes which may lead to bone loss, these alterations in sCD200 and sCD200R1 levels seen under conditions of bed rest were abolished or attenuated. Our results suggest that measurement of sCD200 and/or sCD200R1 may prove a useful and rapid means of monitoring subjects at risk of bone loss and/or accessing the efficacy of treatment regimes designed to counter bone loss. © 2013 Elsevier Inc. Source

Lacny S.,University of Calgary | Wilson T.,University of Calgary | Clement F.,University of Calgary | Roberts D.J.,University of Calgary | And 7 more authors.
Clinical Orthopaedics and Related Research

Background: Although Kaplan-Meier survival analysis is commonly used to estimate the cumulative incidence of revision after joint arthroplasty, it theoretically overestimates the risk of revision in the presence of competing risks (such as death). Because the magnitude of overestimation is not well documented, the potential associated impact on clinical and policy decision-making remains unknown. Questions/purposes: We performed a meta-analysis to answer the following questions: (1) To what extent does the Kaplan-Meier method overestimate the cumulative incidence of revision after joint replacement compared with alternative competing-risks methods? (2) Is the extent of overestimation influenced by followup time or rate of competing risks? Methods: We searched Ovid MEDLINE, EMBASE, BIOSIS Previews, and Web of Science (1946, 1980, 1980, and 1899, respectively, to October 26, 2013) and included article bibliographies for studies comparing estimated cumulative incidence of revision after hip or knee arthroplasty obtained using both Kaplan-Meier and competing-risks methods. We excluded conference abstracts, unpublished studies, or studies using simulated data sets. Two reviewers independently extracted data and evaluated the quality of reporting of the included studies. Among 1160 abstracts identified, six studies were included in our meta-analysis. The principal reason for the steep attrition (1160 to six) was that the initial search was for studies in any clinical area that compared the cumulative incidence estimated using the Kaplan-Meier versus competing-risks methods for any event (not just the cumulative incidence of hip or knee revision); we did this to minimize the likelihood of missing any relevant studies. We calculated risk ratios (RRs) comparing the cumulative incidence estimated using the Kaplan-Meier method with the competing-risks method for each study and used DerSimonian and Laird random effects models to pool these RRs. Heterogeneity was explored using stratified meta-analyses and metaregression. Results: The pooled cumulative incidence of revision after hip or knee arthroplasty obtained using the Kaplan-Meier method was 1.55 times higher (95% confidence interval, 1.43–1.68; p < 0.001) than that obtained using the competing-risks method. Longer followup times and higher proportions of competing risks were not associated with increases in the amount of overestimation of revision risk by the Kaplan-Meier method (all p > 0.10). This may be due to the small number of studies that met the inclusion criteria and conservative variance approximation. Conclusions: The Kaplan-Meier method overestimates risk of revision after hip or knee arthroplasty in populations where competing risks (such as death) might preclude the occurrence of the event of interest (revision). Competing-risks methods should be used to more accurately estimate the cumulative incidence of revision when the goal is to plan healthcare services and resource allocation for revisions. © 2015, The Association of Bone and Joint Surgeons®. Source

Lacny S.,University of Calgary | Marshall D.A.,University of Calgary | Marshall D.A.,Alberta Bone and Joint Health Institute | Marshall D.A.,McCaig Institute for Bone and Joint Health | And 7 more authors.
British Journal of Sports Medicine

Background/aim The risk of injury among Pee Wee (ages 11-12 years) ice hockey players in leagues that allow body checking is threefold greater than in leagues that do not allow body checking. We estimated the cost-effectiveness of a no body checking policy versus a policy that allows body checking in Pee Wee ice hockey. Methods Cost-effectiveness analysis alongside a prospective cohort study during the 2007-2008 season, including players in Quebec (n=1046), where policy did not allow body checking, and in Alberta (n=1108), where body checking was allowed. Injury incidence rates (injuries/1000 player-hours) and incidence proportions (injuries/100 players), adjusted for cluster using Poisson regression, allowed for standardised comparisons and meaningful translation to community stakeholders. Based on Alberta fee schedules, direct healthcare costs (physician visits, imaging, procedures) were adjusted for cluster using bootstrapping. We examined uncertainty in our estimates using cost-effectiveness planes. Results Associated with significantly higher injury rates, healthcare costs where policy allowed body checking were over 2.5 times higher than where policy disallowed body checking ($C473/1000 player-hours (95% CI $C358 to $C603) vs $C184/1000 player-hours (95% CI $C120 to $C257)). The difference in costs between provinces was $C289/1000 player-hours (95% CI $C153 to $C432). Projecting results onto Alberta Pee Wee players registered in the 2011-2012 season, an estimated 1273 injuries and $C213 280 in healthcare costs would be avoided during just one season with the policy change. Conclusion Our study suggests that a policy disallowing body checking in Pee Wee ice hockey is cost-saving (associated with fewer injuries and lower costs) compared to a policy allowing body checking. As we did not account for long-term outcomes, our results underestimate the economic impact of these injuries. © 2014 BMJ Publishing Group Ltd & British Association of Sport and Exercise Medicine. Source

Weljie A.M.,University of Calgary | Bondareva A.,McCaig Institute for Bone and Joint Health | Zang P.,University of Calgary | Jirik F.R.,McCaig Institute for Bone and Joint Health
Journal of Biomolecular NMR

Hypoxia can promote invasive behavior in cancer cells and alters the response to therapeutic intervention as a result of changes in the expression many genes, including genes involved in intermediary metabolism. Although metabolomics technologies are capable of simultaneously measuring a wide range of metabolites in an untargeted manner, these methods have been relatively under utilized in the study of cancer cell responses to hypoxia. Thus, 1H NMR metabolomics was used to examine the effects of hypoxia in the MDA-MB-231 human breast cancer cell line, both in vitro and in vivo. Cell cultures were compared with respect to their metabolic responses during growth under either hypoxic (1% O2) or normoxic conditions. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify a set of metabolites that were responsive to hypoxia. Via intracardiac administration, MDA-MB-231 cells were also used to generate widespread metastatic disease in immuno-compromised mice. Serum metabolite analysis was conducted to compare animals with and without a large tumor burden. Intriguingly, using a cross-plot of the OPLS loadings, both the in vitro and in vivo samples yielded a subset of metabolites that were significantly altered by hypoxia. These included primarily energy metabolites and amino acids, indicative of known alterations in energy metabolism, and possibly protein synthesis or catabolism. The results suggest that the metabolite pattern identified might prove useful as a marker for intra-tumoral hypoxia. © 2011 Springer Science+Business Media B.V. Source

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