Neil Binkley

University of Wisconsin–Madison, Madison, Wisconsin, United States

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Publications (285)907.42 Total impact

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    ABSTRACT: Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary SHOTZ study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 µg/d (s.c. injection) or ZOL 5 mg/y (i.v. infusion). A second biopsy was performed at month 24. Here we report longitudinal changes between and within each treatment group in the cancellous, endocortical, intracortical, and periosteal bone envelopes in patients with evaluable biopsies at months 6 and 24 (paired data set: TPTD, n = 10; ZOL, n = 9). Between-group differences are also reported in the larger set of patients with evaluable biopsies at month 6 (TPTD, n = 28; ZOL, n = 30). Data from the cancellous envelope at month 6 or month 24 provided a reference to compare differences across envelopes within each treatment group. The 24-month results extend our earlier report that TPTD and ZOL possess different tissue-level mechanisms of action. Moreover, these differences persisted for at least 2 years in all 4 bone envelopes. Few longitudinal differences were observed within or across bone envelopes in ZOL-treated patients, suggesting that the low bone formation indices at month 6 persisted to month 24. Conversely, the magnitude of the effect of TPTD on bone formation varied across individual envelopes: median values for mineralizing surface (MS/BS) and bone formation rate (BFR/BS) at month 6 were approximately 3- to 5-fold higher in the endocortical and intracortical envelopes compared to the cancellous envelope. While MS/BS and BFR/BS declined in these envelopes at month 24, median values continued to exceed, or were not significantly different from, those in the cancellous envelope. This study demonstrates for the first time that bone formation indices are higher with TPTD treatment than with ZOL in all 4 bone envelopes and the difference persists for at least 2 years. Moreover, the magnitude of the effect of TPTD in cortical bone remains robust at 24 months. This article is protected by copyright. All rights reserved.
    No preview · Article · Feb 2016 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: Objectives: Sarcopenia increases falls and fracture risk. Sarcopenia clinical trials require robust quantitative tools to evaluate muscle function; jumping mechanography (JM) is likely one such tool. However, US data comparing JM with traditional tests across the lifespan is limited. This study evaluated the effect of age and sex on JM compared with traditional function tests and lean mass. Methods: US adults (213 women/119 men; mean age 65.4 years, range 27-96) performed functional tests including JM, Short Physical Performance Battery (SPPB) and grip strength (GS). Appendicular lean mass (ALM) was measured using DXA. Results: Men had higher relative jump power [mean (SD) 28.5 (10.52) vs. 21.9 (7.11) W/kg], GS [35.5 (9.84) vs. 22.7 (6.98) kg] and ALM/ht(2) [8.25 (1.35) vs. 6.99 (1.38) kg/m(2)] (all p<0.0001); no difference was observed for SPPB components. JM parameters were more strongly correlated with age than traditional tests (R(2)=0.38-0.61 vs. R(2)=0.01-0.28) and weakly with GS and chair rise time (R(2)=0.30-0.36). Conclusion: JM parameters are correlated with GS and chair rise time and demonstrate stronger correlations with age. JM shows promise as a valuable tool to evaluate and monitor interventions for sarcopenia as it could potentially detect change in muscle function more precisely than existing tools.
    Full-text · Article · Dec 2015 · Journal of musculoskeletal & neuronal interactions
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    ABSTRACT: PURPOSE: For patients undergoing CT colonography (CTC), the screening presents an opportunity for concurrent osteoporosis screening, without increasing radiation exposure or the time involved for the patient, using proximal femur quantitative CT-CT x-ray absorptiometry (QCT-CTXA). METHODS: This cohort included 129 women and 112 men (mean age: 60.1 ± 8.2 years; range: 50-95 years) who underwent CTC between March 2013 and September 2014. Areal bone mineral density (BMD; g/cm(2)), and resultant left femoral neck T-score, was prospectively measured on the supine CT series. QCT results were reported with the CTC. Chart review evaluated whether the patients were eligible for BMD screening according to guidelines from the US Preventive Services Task Force and the National Osteoporosis Foundation guidelines; whether they had undergone prior BMD testing; and whether QCT results changed patient management. RESULTS: Overall, 68.0% (164 of 241) of patients from this cohort had not previously undergone BMD screening. According to the National Osteoporosis Foundation guidelines, 44.0% (106 of 241) of patients were eligible for screening. T-scores within the osteopenic and osteoporotic range were detected in 32.3% (78 of 241) and 5.0% (12 of 241) of patients, respectively. Of these patients with low BMD, 66.7% (60 of 90) either had not previously undergone screening or were eligible for BMD testing. Reporting of QCT-CTXA T-scores altered management in 9 patients (3.7%) who had low BMD. CONCLUSIONS: Maximizing the pre-existing value from imaging studies is crucial in the current era of health care reform. We demonstrate that colorectal and osteoporosis screening can be combined at CT examination, adding clinical and likely economic value.
    No preview · Article · Oct 2015 · Journal of the American College of Radiology
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    ABSTRACT: Opportunistic osteoporosis screening using abdominal CT scans obtained for other purposes has the potential to increase detection of those at increased risk for fragility fractures. We sought to combine the tasks of density measurement and vertebral fracture assessment on the sagittal view. We confirm that this represents a robust approach and recommend its implementation in clinical practice. Introduction: Opportunistic osteoporosis screening at routine abdominal CT has been proposed by measuring axial (transverse) L1 trabecular attenuation and by sagittal reconstruction for vertebral fracture assessment. We sought to combine this dual evaluation on the sagittal reconstruction alone to improve efficiency. Methods: Routine contrast-enhanced abdominal CT scans performed for any indication on 571 consecutive adults age 60 years or older (mean age 70.7 years) were retrospectively analyzed. These were performed at a single center over a 3-month period. L1 trabecular attenuation was measured using an ovoid region-of-interest on both the transverse and sagittal series. The sagittal reconstruction was also analyzed for moderate-to-severe vertebral compression fractures using the Genant visual semi-quantitative method. Likely osteoporosis was defined by a moderate-to-severe fracture and/or sagittal L1 trabecular attenuation of ≤110 Hounsfield units (HU) (previously found to be >90 % specific for osteoporosis on our calibrated GE CT scanners at 120 kVp). Correlation was made with hip and spine dual X-ray absorptiometry (DXA). Results: Mean absolute difference in L1 trabecular attenuation between transverse and sagittal reconstructions was 6.7 HU (±5.7) or 6.2 %. The transverse and sagittal HU measurements were in agreement (i.e., both measurements above or below this threshold) in 94.5 % of cases at the 110-HU cutoff. A total of 243 (42.3 %) patients had likely osteoporosis by CT criteria, of which only 48 (19.8 %) had previous DXA screening. Conclusion: Assessment of the sagittal view alone at routine abdominal CT for both vertebral fractures and trabecular bone mineral density provides a rapid and effective opportunistic screen for detecting individuals at increased risk for fragility fractures. © 2015 International Osteoporosis Foundation and National Osteoporosis Foundation
    No preview · Article · Sep 2015 · Osteoporosis International
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    ABSTRACT: The primary aim of this study was to assess dietary vitamin D intake and compliance with a recommended vitamin D supplementation program in a collegiate athlete population. Subsequently, associations between dietary intake, compliance with supplementation, and 25-hydroxyvitamin D [25(OH)D] levels were investigated. This study retrospectively reviewed vitamin D data for 256 athletes across 13 sports at one NCAA Division I University. Independent variables were gender, skin tone, sport, season of year, dietary intake of vitamin D, and supplementation compliance. The main outcome measure was serum 25(OH)D. Low vitamin D status was defined as 25(OH)D level less than 30 ng/mL. Supplementation was recommended for athletes with low status. In fall, 35.5% of athletes had levels less than 30 ng/mL. Mean 25(OH)D level declined (P < .001) between fall (40.7 ± 7.5 ng/mL) and winter (32.5 ± 7.3 ng/mL) in non-supplemented athletes. Supplementation increased 25(OH)D levels by 8.5 ± 9.5 ng/mL (95% confidence interval: 6.6 to 10.4) in 12 weeks. On average athletes reported moderate compliance, taking approximately half of their prescribed supplements. There was a weak correlation between percent supplement compliance and 25(OH) D levels (r = 0.257, P = .011). Athletes with better vitamin D status had higher intake of milk (among freshmen only, P = .042) and yogurt (among all athletes, P = .025). Increasing dietary intake of vitamin D-rich foods and moderate to good compliance with recommended supplementation may help collegiate athletes improve or maximize their vitamin D status.
    No preview · Article · Sep 2015 · Athletic Training and Sports Health Care
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    ABSTRACT: Unstandardized laboratory measurement of 25-hydroxyvitamin D (25(OH)D) confounds efforts to develop clinical and public health vitamin D guidelines. The Vitamin D Standardization Program (VDSP), an international collaborative effort, was founded in 2010 to correct this problem. Nearly all published vitamin D research is based on unstandardized laboratory 25(OH)D measurements. While it is impossible to standardize all old data, it may be possible to identify a small subset of prior studies critical to guidelines development. Once identified it may be possible to calibrate their 25(OH)D values to the NIST and Ghent University reference measurement procedures using VDSP methods thereby permitting future guidelines to be based on standardized results. We simulated the calibration of a small set of ten clinical trials of vitamin D supplementation on achieved 25(OH)D under minimal sun exposure. These studies were selected because they played a prominent role in setting the 2010 Vitamin D Dietary Reference Intakes (DRI). Using random-effects meta-regression analysis, Vitamin D External Quality Assessment (DEQAS) data on assay bias was used to simulate the potential bias due to the lack of assay standardization by calibrating the achieved 25(OH)D levels from those 10 studies to: (1) the largest negative; and (2) the largest positive bias from the DEQAS All Laboratory Trimmed Mean (ALTM) for the appropriate assay and year of analysis. For a usual vitamin D intake of 600 IU/day the difference in mean achieved 25(OH)D values for those two options was 20 nmol/L. However, without re-calibration of 25(OH)D values it is impossible to know the degree to which any of the current guidelines may have been biased. This approach may help stimulate the search for and standardization of that small subset of key studies and, in the cases where standardization is impossible; to identify areas of urgently needed vitamin D research. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Aug 2015 · The Journal of steroid biochemistry and molecular biology
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    ABSTRACT: Sarcopenia is common in later life and may be associated with adverse health outcomes such as disability, falls and fracture. There is no consensus definition for its diagnosis although diagnostic algorithms have been proposed by the European Working Group for Sarcopenia in Older People (EWGSOP), the International Working Group on Sarcopenia (IWGS) and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). More recently, Binkley and colleagues devised a score-based system for the diagnosis of "dysmobility syndrome" in an attempt to combine adverse musculoskeletal phenotypes, including sarcopenia and osteoporosis, in order to identify older individuals at particular risk. We applied these criteria to participants from the Hertfordshire Cohort Study to define their prevalence in an unselected cohort of UK community-dwelling older adults and assess their relationships with previous falls and fracture. Body composition and areal bone mineral density were measured using dual-energy X-ray absorptiometry, gait speed was determined by a 3-m walk test and grip strength was assessed with a Jamar hand-held dynamometer. Researcher-administered questionnaires were completed detailing falls and fracture history. The prevalence of sarcopenia in this cohort was 3.3, 8.3 and 2.0 % using the EWGSOP, IWGS and related definition of FNIH, respectively; 24.8 % of individuals had dysmobility syndrome. Individuals with dysmobility reported significantly higher number of falls (last year and since the age of 45 years) (p < 0.01) than those without it, but no increased fracture rate was observed in this group (p = 0.96). Those with sarcopenia as defined by the IWGS reported significantly higher falls in the last year and prevalent fractures (falls in the last year: OR 2.51; CI 1.09-5.81; p = 0.03; fractures OR 2.50; CI 1.05-5.92; p = 0.04) but these significant associations were not seen when the EWGSOP definition was applied. The IWGS definition of sarcopenia appears to be an effective means of identifying individuals at risk of prevalent adverse musculoskeletal events.
    Full-text · Article · Jul 2015 · Calcified Tissue International
  • Neil Binkley · Cyrus Cooper
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    ABSTRACT: In this issue of the Journal of Clinical Densitometry, articles consider sarcopenia epidemiology, current and future approaches to diagnosis, tools to assess muscle mass and/or function, the roles of vitamin D and nutrition in general in sarcopenia, and finally the care of patients with this condition. All authors have taken a clinical approach to their topic area and provide bulleted key messages as the most salient points. Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · Journal of Clinical Densitometry
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    ABSTRACT: Osteoporosis remains under-diagnosed. Routine abdominal CT can provide opportunistic screening, but the effect of IV contrast is largely unknown. The overall performance for predicting osteoporosis was similar between enhanced and unenhanced scans. Therefore, both non-contrast and contrast-enhanced abdominal CT scans can be employed for opportunistic osteoporosis screening. Osteoporosis is an important yet under-diagnosed public health concern. Lumbar attenuation measurement at routine abdominal CT can provide a simple opportunistic initial screen, but the effect of IV contrast has not been fully evaluated. Mean trabecular CT attenuation values (in Hounsfield units, HU) at the L1 vertebral level were measured by oval region-of-interest (ROI) on both the unenhanced and IV-contrast-enhanced CT series in 157 adults (mean age, 62.0). All patients underwent correlative central DXA within 6 months of CT. Based on DXA BMD of the lumbar spine, femoral neck, and total proximal femur: osteoporosis, osteopenia, and normal BMD was present in 33, 77, and 47, respectively. Statistical analysis included Bland-Altman plots and receiver operating characteristic (ROC) curves. Mean difference (±SD) in L1 trabecular attenuation between enhanced and unenhanced CT series was +11.2 HU (±19.2) (95 % CI, 8.16-14.22 HU), an 8 % difference. Intra-patient variation was substantial, but no overall trend in the HU difference was seen according to underlying BMD. ROC area under the curve (AUC) for unenhanced and enhanced CT for diagnosing osteoporosis were similar at 0.818 and 0.830, respectively (p = 0.632). Thresholds for maintaining 90 % specificity for osteoporosis were 90 HU for unenhanced and 102 HU for enhanced CT. Thresholds for maintaining 90 % sensitivity for osteoporosis were 139 HU for unenhanced and 144 HU for enhanced CT. Similar diagnostic performance was seen for diagnosing low BMD (osteoporosis or osteopenia) using higher HU cut-offs. Contrast-enhanced CT shows an average increase of 11 HU over the unenhanced series for L1 trabecular attenuation. The overall performance for predicting osteoporosis is similar between the enhanced and unenhanced scans, thus either can be employed for initial opportunistic screening.
    No preview · Article · Jul 2015 · Osteoporosis International

  • No preview · Article · Jul 2015 · Journal of Clinical Densitometry

  • No preview · Article · Jul 2015 · Journal of Clinical Densitometry
  • Ellen Fidler · Diane Krueger · Neil Binkley

    No preview · Article · Jul 2015 · Journal of Clinical Densitometry
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    ABSTRACT: To investigate the relationship between serum 25-hydroxyvitamin D (25[OH]D) levels and nuclear cataract among participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI) Observational Study (OS). Nuclear cataract was assessed from slit lamp photographs (2001-2004) taken 6 years after collecting serum analyzed for 25(OH)D levels at WHI baseline (1994-1998) in 1278 CAREDS participants age 50 to 79 years. Multivariate (age, iris color, smoking, pulse pressure) odds ratios (ORs) for nuclear cataract (nuclear opacities > level 4 or cataract extraction) by quintiles of serum 25(OH)D were estimated using logistic regression. No significant association was observed between serum 25(OH)D and nuclear cataract among women of all ages (age-adjusted OR [95% confidence interval (CI)] 0.97 [0.65-1.45]). However, there was a significant age interaction (P for interaction = 0.04). There were no significant associations in the women 70 years or older. In women younger than 70 years, we observed an inverse association between serum 25(OH)D and nuclear cataract (multivariate adjusted ORs [95% CI] 0.54 [0.29-0.99] and 0.66 [0.36-1.20] for quintiles 4 and 5 vs. 1, respectively; P = 0.03). Further adjustment for 25(OH)D determinants (body mass index, vitamin D intake, and UVB exposure) attenuated this association. Serum 25(OH)D levels were unrelated to nuclear opacities in this study sample. However, exploratory analyses suggest a protective association in women younger than 70 years. Further investigations of the relationship between vitamin D and nuclear lens opacities are warranted.
    No preview · Article · Jul 2015 · Investigative ophthalmology & visual science
  • Jessie Libber · Diane Krueger · Neil Binkley

    No preview · Article · Jul 2015 · Journal of Clinical Densitometry
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    ABSTRACT: New densitometer installation requires cross-calibration for accurate longitudinal assessment. When replacing a unit with the same model, the International Society for Clinical Densitometry recommends cross-calibrating by scanning phantoms 10 times on each instrument and states that spine bone mineral density (BMD) should be within 1%, whereas total body lean, fat, and %fat mass should be within 2% of the prior instrument. However, there is limited validation that these recommendations provide adequate total body cross-calibration. Here, we report a total body cross-calibration experience with phantoms and humans.
    No preview · Article · Jun 2015 · Journal of Clinical Densitometry

  • No preview · Article · Jun 2015
  • Joan M Lappe · Neil Binkley
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    ABSTRACT: Maintenance of adequate vitamin D status is a stratagem to consider for sarcopenia prevention and treatment. Vitamin D deficiency is common and involves all ages of most racial/ethnic groups and both sexes. Evidence suggests that vitamin D is important for muscle strength and function, and prospective studies are underway to further define these effects. This article summarizes the potential effects of vitamin D on skeletal muscle structure and function and provides guidance for vitamin D supplementation in prevention and treatment of sarcopenia and falls. Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Journal of Clinical Densitometry
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    ABSTRACT: Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g. diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · May 2015 · Bone
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    ABSTRACT: Women with type 1 diabetes (T1DM) have an elevated fracture risk. We therefore compared the associations of health behaviors and clinical factors with bone mineral density (BMD) and bone remodeling between premenopausal women with and without T1DM to inform potential interventions. Participants included women with T1DM (n = 89) from the Wisconsin Diabetes Registry Study and age- and race-matched controls without diabetes (n = 76). Peripheral (heel, forearm) and central (hip, spine) BMD, markers of bone resorption and formation, bone cell signaling, glycemic control, and kidney function were assessed. Health behaviors and medical history were self-reported. In controls, but not in women with T1DM, older age was associated with lower bone resorption (p < 0.006) and formation (p = 0.0007). Body mass index (BMI) was positively associated with heel and forearm BMD in both controls and T1DM women (all p < 0.0001), but with hip and spine BMD only in controls (p < 0.005). Worse glycemic control during the previous 10 years, greater alcohol intake, history of smoking, and lack of physical activity were associated with poorer bone outcomes only in women with T1DM (all p < 0.002); whereas use of hormonal contraceptives was related to low bone formation in both women with and without T1DM (all p < 0.006). Diabetes duration, insulin dose, residual C-peptide, and kidney function were not associated with bone in T1DM. Age and BMI may not predict bone health in T1DM women. However modifiable behaviors such as optimizing glycemic control, limiting substance and hormonal contraceptive use, and increasing physical activity may improve bone health in T1DM women. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · Diabetes/Metabolism Research and Reviews
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    ABSTRACT: It is unclear if vitamin D supplementation improves central blood pressure or arterial stiffness in Native American (NA) women. Healthy postmenopausal NA women were randomized to receive 400 IU or 2500 IU of vitamin D for 6 months. Central systolic blood pressure (cSBP), central pulse pressure (cPP) and aortic augmentation index (AIx) were estimated by tonometry at baseline and after 6 months. Study volunteers (n = 98) were 61 (7.3) years old. 25(OH)D was 26.4 (11.0) ng/mL. 25(OH)D was similar between the two treatment groups (p = 0.291), as were baseline cSBP, cPP, and CVD risk factors (all p > 0.1). Treatment with 2500 IU of daily vitamin D3 did not affect cSBP, cPP, or AIx (all p > 0.1) compared to 400 IU daily. Despite low serum 25(OH)D at baseline, 6 months of vitamin D supplementation did not improve central blood pressure parameters or arterial stiffness in NA women. CLINICAL TRIALS. NCT01490333. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Apr 2015 · Atherosclerosis

Publication Stats

9k Citations
907.42 Total Impact Points

Institutions

  • 1994-2015
    • University of Wisconsin–Madison
      • • Department of Medicine
      • • Department of Biochemistry
      • • School of Medicine and Public Health
      • • Institute on Aging
      • • School of Pharmacy
      • • Wisconsin National Primate Research Center
      • • Department of Medical Sciences
      Madison, Wisconsin, United States
  • 2003
    • University of Vermont
      Burlington, Vermont, United States
  • 1998-2000
    • Wisconsin National Primate Research Center
      Madison, Wisconsin, United States