Neil Binkley

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

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Publications (262)816.37 Total impact

  • 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.
    Journal of Clinical Densitometry 07/2015; DOI:10.1016/j.jocd.2015.05.067 · 1.60 Impact Factor
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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.
    Osteoporosis International 07/2015; DOI:10.1007/s00198-015-3224-9 · 4.17 Impact Factor
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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.
    Journal of Clinical Densitometry 06/2015; DOI:10.1016/j.jocd.2015.04.003 · 1.60 Impact Factor
  • 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.
    Journal of Clinical Densitometry 06/2015; DOI:10.1016/j.jocd.2015.04.015 · 1.60 Impact Factor
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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.
    Bone 05/2015; 78. DOI:10.1016/j.bone.2015.05.016 · 4.46 Impact Factor
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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.
    Diabetes/Metabolism Research and Reviews 05/2015; 31(4). DOI:10.1002/dmrr.2627 · 3.59 Impact Factor
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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.
    Atherosclerosis 04/2015; 240(2):526-528. DOI:10.1016/j.atherosclerosis.2015.04.795 · 3.97 Impact Factor
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    ABSTRACT: Vitamin D metabolites are widely studied for their roles in bone health, immune functions, and other potential physiologic roles in humans. However, the optimal blood levels of vitamin D metabolites are still unclear. Various methods for measuring vitamin D metabolites have been used and recently liquid chromatography tandem mass spectroscopy (LC-MS/MS) has been adopted as the gold standard for vitamin D metabolite measurement. Here, we report the use of LC-MS/MS to measure 25-hydroxyvitamin D (25(OH)D2&3 ), and 1,25-dihydroxyvitamin D (1,25(OH)2 D2&3 ), in three laboratory nonhuman primate species: common marmoset (Callithrix jacchus), rhesus macaque (Macaca mulatta), and cynomolgus macaque (Macaca fascicularis), and compare them to humans using the same technique. The nonhuman primates showed blood levels for 25(OH)D3 and 1,25(OH)2 D3 significantly higher than human values with marmosets having the highest levels. Marmoset samples showed significantly more variability among individuals than those from macaques for both metabolites, but all three nonhuman primate species exhibited large variation within species for both 25(OH)D2&3 and 1,25(OH)2 D2&3 . Marmoset females had significantly lower values than the males for 25(OH)D3 , while rhesus males showed a significant decrease in 25(OH)D3 with age. The most striking finding is the variation within species for vitamin D levels even in laboratory primates that have a controlled diet, UV exposure, and in some cases, genetic constraints. Similar variation in 25(OH)D responses to a fixed dose of oral vitamin D supplementation has been reported in humans. We suggest that these species can provide primate models for examining the factors influencing variation in the levels of vitamin D necessary for human and nonhuman primate health. Am. J. Primatol. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Primatology 04/2015; 77(7). DOI:10.1002/ajp.22403 · 2.14 Impact Factor
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    ABSTRACT: The 2014 Santa Fe Bone Symposium provided a setting for the presentation and discussion of the clinical relevance of recent advances in the fields of osteoporosis and metabolic bone disease. The format included oral presentations of abstracts by endocrinology fellows, plenary lectures, panel discussions and breakout sessions, with ample opportunities for informal discussions before and after scheduled events. Topics addressed in these proceedings included a review of the important scientific publications in the past year, fracture prevention in patients with dysmobility and immobility, fracture liaison services for secondary fracture prevention, management of pre-menopausal osteoporosis, the role of bone microarchitecture in determining bone strength, measurement of microarchitecture in clinical practice and methods to improve the quality of bone density testing. This is a report of the proceedings of the 2014 Santa Fe Bone Symposium.
    Endocrine Research 03/2015; 40(2). DOI:10.3109/07435800.2015.1005746 · 1.41 Impact Factor
  • Diane Krueger, Jessie Libber, Neil Binkley
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    ABSTRACT: Trabecular bone score (TBS) is related to microarchitecture and fracture risk independently of bone mineral density (BMD) and clinical risk factors. Widespread clinical TBS use requires documentation of reproducibility and ideally comparability across scanners. This study evaluated TBS reproducibility and explored differences between Lunar Prodigy and iDXA densitometers. Reproducibility was assessed from replicate scans in 210 men and women participating in various dual-energy X-ray absorptiometry (DXA) precision assessments. iDXA-to-Prodigy comparability was evaluated using 155 participants from 3 study groups. L1-L4 BMD and TBS precision was similar on iDXA and Prodigy (BMD coefficient of variation = 1.9% and 1.5% and TBS coefficient of variation = 1.4% and 1.6%, respectively). Precision did not differ between men and women; however, between-technologist differences (p < 0.05) of similar magnitude were observed for both BMD and TBS. Prodigy-to-Prodigy TBS values were highly correlated (R(2) = 0.85 with bias of -0.010 TBS units). Agreement was less robust comparing Prodigy with iDXA instruments (TBS R(2): 0.72-0.81 with biases of 0.012-0.034 TBS units). In conclusion, TBS precision is comparable to that of BMD and does not differ between men and women. Additionally, in these cohorts, slight TBS differences were observed between iDXA and Prodigy scans. These data suggest a potential difference between densitometer models perhaps due to higher iDXA image resolution. Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.
    Journal of Clinical Densitometry 02/2015; 18(2). DOI:10.1016/j.jocd.2014.11.003 · 1.60 Impact Factor
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    ABSTRACT: Summary Substantial variability exists in the serum 25(OH)D increase observed in response to vitamin D supplementation. Measurement of circulating cholecalciferol and 24,25(OH)2D, as indicators of vitamin D absorption and degradation, respectively, account for approximately half of the variation in serum 25(OH)D observed following supplementation. Introduction Vitamin D supplementation produces a variable response in serum 25(OH)D. This variability likely reflects, in part, differences in vitamin D absorption and/or degradation. Despite this variation in response, virtually all expert recommendations endorse a fixed vitamin D supplementation dose, an approach also used in most prospective studies. Such utilization of a single vitamin D dose does not assure attaining any pre-specified target 25(OH)D level, thereby compromising clinical care and prospective supplementation trials. This study begins addressing this weakness by exploring the feasibility of vitamin D metabolite measurements to predict serum 25(OH)D level attained following supplementation. Methods Ninety-one community-dwelling postmenopausal women with baseline 25(OH)D of 10–30 ng/mL received oral vitamin D3, 2300 or 2500 IU, daily for 4–6 months. Serum 25(OH)D, cholecalciferol (D3), and 24,25(OH)2D were measured before and at the end of supplementation to determine if metabolite concentrations allow prediction of the 25(OH)D level attained. Results From baseline and follow-up data, we derived a multiple linear regression model predicting posttreatment 25(OH)D as follows: final 25(OH)D = 8.3 + (1.05*initial 25(OH)D) − (7.7*initial 24,25(OH)2D) + (0.53*final D3) + (4.2*final 24,25(OH)2D). This model has an adjusted R 2 = 0.55, thus accounting for approximately half of the observed variance in the final 25(OH)D level. Conclusions The contributions of circulating cholecalciferol and 24,25(OH)2D to this predictive model can be considered as indicators of intestinal absorption and clearance, respectively. This paradigm requires further study; it may allow efficient “treat-to-25(OH)D-target” strategies useful in optimizing prospective studies and clinical practice.
    Osteoporosis International 01/2015; 26(5). DOI:10.1007/s00198-014-3010-0 · 4.17 Impact Factor
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    ABSTRACT: Summary Bone health may be negatively impacted by childhood socio-environmental circumstances. We examined the independent associations of single-parent childhood and parental death or divorce in childhood with adult bone strength indices. Longer exposure to a single-parent household in childhood was associated with lower bone strength in adulthood. Introduction Because peak bone mass is acquired during childhood, bone health may be negatively impacted by childhood socio-environmental disadvantage. The goal of this study was to determine whether being raised in a single-parent household is associated with lower bone strength in adulthood. Methods Using dual-energy X-ray absorptiometry data from 708 participants (mean age 57 years) in the Midlife in the United States Biomarker Project, we examined the independent associations of composite indices of femoral neck bone strength relative to load (in three failure modes: compression, bending, and impact) in adulthood with the experience of single-parent childhood and parental death or divorce in childhood. Results After adjustment for gender, race, menopause transition stage, age, and body mass index, each additional year of single-parent childhood was associated with 0.02 to 0.03 SD lower indices of adult femoral neck strength. In those with 9–16 years of single-parent childhood, the compression strength index was 0.41 SD lower, bending strength index was 0.31 SD lower, and impact strength index was 0.25 SD lower (all p values Conclusions Independent of parental death or divorce, growing up in a single-parent household is associated with lower femoral neck bone strength in adulthood, and this association is not entirely explained by childhood or adult socioeconomic conditions or lifestyle choices.
    Osteoporosis International 12/2014; 26(3). DOI:10.1007/s00198-014-2990-0 · 4.17 Impact Factor
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    ABSTRACT: Summary Improved approaches to assess functional change over time are needed to optimally reduce fall/fracture risk; jumping mechanography (JM) may be one such methodology. In this study, JM parameters were more reproducible than traditional functional tests. JM may be better able to demonstrate efficacy of interventions to mitigate sarcopenia. Introduction Jumping mechanography (JM), a tool using maximal countermovement jumps performed on a force plate, may more reliably assess muscle function than traditional methods. The purpose of this study was to examine JM retest reliability in older adults compared with commonly used muscle and physical function assessments. Methods Community-dwelling individuals age ≥70 years performed physical and muscle function assessments including the short physical performance battery (SPPB), grip strength, and JM on multiple occasions over 3 months. JM parameters included body weight-corrected peak power and jump height. Appendicular lean mass was measured by dual energy x-ray (DXA). Mixed effects linear regression models were used to estimate between- and within-person variability summarized as intra-class correlation coefficients (ICC). Results Ninety-seven individuals (49 females, 48 males, mean age 80.7 years) participated. All testing was well tolerated; no participant sustained injury. Jump power, height, and grip strength were greater (p SPPB score, and gait speed had lower ICCs (0.81, 0.77, and 0.76, respectively). Conclusion In older adults, JM has excellent retest reliability, is stable over time, and can be performed safely. JM retest reliability was comparable to grip strength and possibly better than SPPB and gait speed. JM is a promising tool for muscle function assessment in older adults. Comparison of this approach with traditional assessment tools in longitudinal interventional studies is needed.
    Osteoporosis International 12/2014; 26(2). DOI:10.1007/s00198-014-2983-z · 4.17 Impact Factor
  • IOF Regionals - 5h Asia-Pacific Osteoporosis Meeting; 11/2014
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    ABSTRACT: Osteoporosis becomes common with aging in both sexes, but is often ignored in men. The 2013 International Society for Clinical Densitometry consensus conference endorsed a Caucasian female referent database for T-score calculation in men. This recommendation has generated controversy and concern. Accumulating data indicate that at the same DXA-measured body mineral density (BMD) (g/cm(2)), men and women are at approximately the same fracture risk. With this point in mind, using the same database to derive the T-score in men and women is reasonable. As a result, a greater proportion of men who sustain a fragility fracture will have T-scores that are higher than they would if a male database were used; in fact, many men will fracture at T-scores that are "normal." This highlights the importance of diagnosing osteoporosis not just by T-score, but also by the presence of fragility fracture and/or by estimations of fracture risk as generated by tools such as the FRAX calculator. The practical consequences of this change in densitometric definition of osteoporosis in men should be monitored, including the proportion of men at risk identified and treated as well as defining the response to treatment in those assessed by this more comprehensive approach.
    Current Osteoporosis Reports 09/2014; DOI:10.1007/s11914-014-0242-z
  • Neil Binkley, Christopher T. Sempos
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    ABSTRACT: For a number of years it has been widely assumed that measurement of serum 25-hydroxyvitamin D [25(OH)D] concentration is the best approach to assessing an individual's vitamin D status(1,2). However, it has also been recognized that there is substantial within assay variation in 25(OH)D measurement and even greater between-assay variability (3-5). Such assay variation clearly confounds attempts to define what constitutes the diagnosis of hypovitaminosis D. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2014; 29(8). DOI:10.1002/jbmr.2252 · 6.59 Impact Factor
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    ABSTRACT: The effect of an investigational oral calcitonin tablet upon bone mineral density (BMD) of the spine was investigated in postmenopausal women with low bone mass and at increased risk of fracture. Compared to placebo, calcitonin tablets increased lumbar spine BMD. This agent may provide an additional choice for patients. An investigational oral salmon calcitonin preparation was previously shown to increase lumbar spine BMD in postmenopausal women with osteoporosis. Our objective was to evaluate the use of this agent in postmenopausal women with low bone mass and at increased fracture risk but not meeting BMD criteria for osteoporosis. Treatment-na < ve women were randomized to receive oral recombinant salmon calcitonin tablets or placebo once daily for 1 year. Dual-energy X-ray absorptiometry was performed at baseline and at study weeks 28 and 54. CTx-1, a bone resorption marker, was obtained at the same time points. Subjects returned periodically for tolerability assessment and adverse event (AE) recording. One hundred twenty-nine women in the USA were randomized, 86 to calcitonin and 43 to placebo. Calcitonin recipients experienced a significant increase from baseline in lumbar spine BMD; the difference compared with placebo was significant. Dosing at bedtime or with dinner was equally effective. CTx-1 was suppressed in calcitonin recipients but not in placebo subjects. Gastrointestinal AEs were common, but the overall safety profile was comparable between groups. Oral calcitonin may provide a useful therapeutic alternative for some women with low bone mass.
    Osteoporosis International 07/2014; 25(11). DOI:10.1007/s00198-014-2796-0 · 4.17 Impact Factor
  • Journal of Clinical Densitometry 07/2014; 17(3):401–402. DOI:10.1016/j.jocd.2014.04.016 · 1.60 Impact Factor
  • Journal of Clinical Densitometry 07/2014; 17(3):399–400. DOI:10.1016/j.jocd.2014.04.010 · 1.60 Impact Factor
  • Journal of Clinical Densitometry 07/2014; 17(3):408. DOI:10.1016/j.jocd.2014.04.036 · 1.60 Impact Factor

Publication Stats

7k Citations
816.37 Total Impact Points

Institutions

  • 1994–2015
    • University of Wisconsin–Madison
      • • Department of Medicine
      • • Department of Biochemistry
      • • School of Medicine and Public Health
      • • Wisconsin National Primate Research Center
      • • Institute on Aging
      Madison, Wisconsin, United States
  • 2009
    • University of Wisconsin - Stout
      Menominee, Wisconsin, United States
  • 2008
    • New Mexico Clinical Research and Osteoporosis Center
      Albuquerque, New Mexico, United States
  • 2003–2006
    • University of Vermont
      Burlington, Vermont, United States
  • 2005
    • Medical College of Wisconsin
      Milwaukee, Wisconsin, United States
  • 1998–2000
    • Wisconsin National Primate Research Center
      Madison, Wisconsin, United States