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Comparison of Methods for Improving Fracture Risk Assessment in Diabetes: The Manitoba BMD Registry.

ABSTRACT: Type 2 diabetes is a risk factor for fracture independent of FRAX (fracture risk assessment) probability. We directly compared four proposed methods to improve the performance of FRAX for type 2 diabetes by: (1) including the rheumatoid arthritis (RA) input to FRAX; (2) making a trabecular bone score (TBS) adjustment to FRAX; (3) reducing the femoral neck T-score input to FRAX by 0.5 SD; and (4) increasing the age input to FRAX by 10 years. We examined major osteoporotic fractures (MOFs) and hip fractures (HFs) over a mean of 8.3 years observation among 44,543 women and men 40 years of age or older (4136 with diabetes) with baseline lumbar spine and hip DXA from 1999 through 2016. Controlled for unadjusted FRAX probability, diabetes was associated with an increased risk for MOFs and HFs. All four FRAX adjustments attenuated the effect of diabetes, but a residual effect of diabetes was seen on MOF risk after TBS adjustment, and on HF risk after the RA and TBS adjustments. Among those with diabetes, unadjusted FRAX risk underestimated MOF (observed/predicted ratio 1.15; 95% CI, 1.03 to 1.28), but this was no longer significant after applying the diabetes adjustments. HF risk was more severely underestimated (observed/predicted ratio 1.85; 95% CI, 1.51 to 2.20) and was only partially corrected with the diabetes adjustments (still significant for the RA and TBS adjustments). Among those with diabetes, there was moderate reclassification based upon a fixed MOF cut-off of 20% (4.1% to 7.1%) or fixed HF cut-off of 3% (5.7% to 16.5%). Net reclassification improvement increased for MOF with each of the diabetes adjustments (range 3.9% to 5.6% in the diabetes subgroup). In conclusion, each of the proposed methods for addressing limitations in the ability of FRAX to assess fracture risk in individuals with diabetes was found to improve performance, though no single method was optimal in all settings. © 2018 American Society for Bone and Mineral Research.

SUBMITTER: Leslie WD

PROVIDER: S-EPMC6193547 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Comparison of Methods for Improving Fracture Risk Assessment in Diabetes: The Manitoba BMD Registry.

Leslie William D WD Johansson Helena H McCloskey Eugene V EV Harvey Nicholas C NC Kanis John A JA Hans Didier D

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20180716 11

Type 2 diabetes is a risk factor for fracture independent of FRAX (fracture risk assessment) probability. We directly compared four proposed methods to improve the performance of FRAX for type 2 diabetes by: (1) including the rheumatoid arthritis (RA) input to FRAX; (2) making a trabecular bone score (TBS) adjustment to FRAX; (3) reducing the femoral neck T-score input to FRAX by 0.5 SD; and (4) increasing the age input to FRAX by 10 years. We examined major osteoporotic fractures (MOFs) and hip ...[more]

PMID: 29953670

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Project description:Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men (MrOS) study comprises men ≥65 years old in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multidimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4.6 years for changes in femoral neck bone mineral density (BMD) and for incident hip fracture. Change in BMD was determined from mixed effects regression models taking age and weight into account. Participants were categorized into three groups: BMD maintenance (no decline; estimated change ≥0 g/cm2 , n = 453); expected loss (estimated change 0 to 1 SD below the estimated mean change, -0.034 g/cm2 for femoral neck, n = 1184); and accelerated loss (estimated change ≥1 SD below mean change, n = 237). Differential abundance values of 3946 peptides were summarized by meta-analysis to determine differential abundance of each of 339 corresponding proteins for accelerated BMD loss versus maintenance. Using this meta-analytic standardized fold change at cutoffs of ≥1.1 or ≤0.9 (p < 0.10), 20 proteins were associated with accelerated BMD loss. Associations of those 20 proteins with incident hip fracture were tested using Cox proportional hazards models with age and BMI adjustment in 2473 men. Five proteins were associated with incident hip fracture (HR between 1.29 and 1.41 per SD increase in estimated protein abundance). Some proteins have been previously associated with fracture risk (eg, CD14 and SHBG), whereas others have roles in cellular senescence and aging (B2MG and TIMP1) and complement activation and innate immunity (CO7, CO9, CFAD). These findings may inform development of biomarkers for future research in bone biology and fracture prediction. © 2017 American Society for Bone and Mineral Research.

Project description:ObjectivesFracture liaison services are designed to identify patients needing osteoporosis treatment after a fracture. Some fracture liaison service designs involve a prescreening step, for example, fracture risk assessment tool (FRAX®). Another possible prescreening tools are bone mass density assessment in the acute setting. The aim of this study was to assess the effectiveness of prescreening tools.MethodsIn the present prospective cohort study, women aged >55 years with a radius fracture were included. Patients were recruited at the emergency department after experiencing their fracture. All patients performed fracture risk assessment by fracture risk assessment tool, and bone mass density assessment by digital X-ray radiogrammetry and dual-energy X-ray absorptiometry (prescreening steps) as well as full routine evaluation at the osteoporosis unit (endpoint). The main outcome measures were sensitivity, specificity, predictive values, and area under the curve.ResultsForty-one women were recruited (mean age: 70 ± 8 years). Of these, 54% fulfilled the treatment indication criteria of osteoporosis after a full examination. Fracture risk assessment tool without bone mass density (cutoff ⩾ 15%) for prescreening patients had a high sensitivity (90%) but a low area under the curve (0.50) and specificity (16%). The highest area under the curve (0.73) was found prescreening with bone mass density assessment (dual-energy X-ray absorptiometry or digital X-ray radiogrammetry) having a sensitivity of 59%-86% and specificity of 61%-90%.ConclusionThis study, though small, raises questions regarding the effectiveness of using a prescreening step in fracture liaison services for high-risk individuals. In this cohort, FRAX® without bone mass density had a low precision, with a risk of both underestimating and overestimating patients requiring treatment. Bone mass density assessment in the acute setting could improve the precision of prescreening. Further investigations on the effectiveness and health economics of prescreening steps in fracture liaison services are needed.

Project description:The ability of bone mineral density (BMD) and other risk factors to predict fracture risk is well-established for as long as 5 to 10 years. However, their value to predict risk over a longer term has not been directly studied. We investigated whether a single assessment of femoral neck BMD and fracture history can predict fracture risk over 20 to 25 years. We used data from the Study of Osteoporotic Fractures (SOF) that assessed BMD and risk factors in 7959 women age ≥67 (mean = 73.4) in 1988-1990. Follow-up for fractures continued for 25 years for hip fracture, and for 20 years for any nonvertebral fracture. Using age-adjusted proportional hazards models, we analyzed the relationships between a single baseline assessment of femoral neck BMD, fracture history and age, and 20-25-year fracture incidence. The 25-year cumulative incidence of hip fracture was 17.9%; 20-year incidence of any nonvertebral fracture was 46.2%. The 25-year hip fracture incidence was highest in those ≥80 years old (22.6%) compared to 13.9% in women aged <70 years. A single femoral neck BMD measurement strongly predicted long-term hip fracture risk to 25 years: 29.6% risk in the lowest BMD quartile versus 7.6% with the highest relative hazard (RH) = 4.9 (95% CI, 4.1 to 6.0). Femoral neck BMD predicted hip fracture with little degradation over time from RH/SD = 2.6 (2.2 to 3.0) for 0 to 5 years to RH/SD = 1.8 (1.4 to 2.4) for 20 to 25 years. Lifetime hip fracture risk was similar (∼30%) regardless of age from 67 to >80 years. History of hip fracture predicted hip fractures only slightly better than history of nonvertebral fracture (RH = 1.6 [95% CI, 1.1 to 2.2] versus RH = 1.4 [95% CI, 1.2 to 1.5], respectively). Fracture history remained strongly predictive up to 25 years. We conclude that a single BMD and fracture history assessment can predict fracture risk over 20 to 25 years. Long-term risk of hip fracture remains extremely high in the oldest age groups, supporting risk assessment and consideration of treatment even in the oldest, highest-risk women.© 2017 American Society for Bone and Mineral Research.

Project description:Prior high-trauma fractures identified through health services data are associated with low bone mineral density (BMD) and future fracture risk to the same extent as fractures without high-trauma.IntroductionSome have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures.MethodsUsing a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40 years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise.ResultsThe study population consisted of 64,428 women and men with no prior fracture (mean age 63.7 years), 858 with prior high-trauma fractures (mean age 65.1 years), and 14,758 with prior low-trauma fractures (mean age 67.2 years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8 years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08-1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47-1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture.ConclusionsHigh-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk.

Project description:For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior). The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS), mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%), however small angular deviations (<15°) were negligible. Differences in the experimental results between the bending tests originate in their respective location of maximal bending moment induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small errors (up to 16.8%, compared to corresponding alignment under unconstrained torsion) due to a parallel offset between the specimens' axis of gravity and the torsional axis of rotation.

Dataset Information

Comparison of Methods for Improving Fracture Risk Assessment in Diabetes: The Manitoba BMD Registry.

Publications

Comparison of Methods for Improving Fracture Risk Assessment in Diabetes: The Manitoba BMD Registry.

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