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Osteoporosis: HELP
Articles by Thomas F. Lang
Based on 22 articles published since 2010
(Why 22 articles?)
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Between 2010 and 2020, T. Lang wrote the following 22 articles about Osteoporosis.
 
+ Citations + Abstracts
1 Review Axial QCT: clinical applications and new developments. 2014

Link, Thomas M / Lang, Thomas F. ·Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA. Electronic address: tmlink@radiology.ucsf.edu. · Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA. ·J Clin Densitom · Pubmed #24880494.

ABSTRACT: Quantitative computed tomography (QCT) is currently undergoing a renaissance, with an increasing number of studies being published and the definition of both QCT-specific osteoporosis thresholds and treatment criteria. Compared with dual-energy X-ray absorptiometry, the current standard bone mineral density technique, QCT has a number of pertinent advantages, including volumetric measurements, less susceptibility to degenerative spine changes, and higher sensitivity to changes in bone mass. Disadvantages include the higher radiation doses and less experience with fracture prediction and therapy monitoring. Over the last 10 yr, a number of novel applications have been described allowing assessment of bone mineral density and bone quality in larger patient populations, developments that may substantially improve patient care.

2 Review Quantitative computed tomography. 2010

Lang, Thomas F. ·Joint Bioengineering Graduate Group, and Department of Radiology and Biomedical Imaging, University of California-San Francisco, San Francisco, CA 94143-0946, USA. Thomas.Lang@Radiology.ucsf.edu ·Radiol Clin North Am · Pubmed #20609894.

ABSTRACT: Unlike dual x-ray absorptiometry and high-resolution CT scan and MR imaging techniques, which are largely restricted to the peripheral skeleton owing to radiation dose and signal-to-noise considerations, volumetric quantitative measures provide measures of cortical and trabecular volumetric bone mineral density, cross-sectional geometry, and estimates of whole-bone strength based on patient specific finite element modeling. This article focuses on the application of volumetric quantitative measures to studies of aging, disuse, and drug treatment as related to osteoporosis.

3 Clinical Trial Spatial Differences in the Distribution of Bone Between Femoral Neck and Trochanteric Fractures. 2017

Yu, Aihong / Carballido-Gamio, Julio / Wang, Ling / Lang, Thomas F / Su, Yongbin / Wu, Xinbao / Wang, Manyi / Wei, Jie / Yi, Chen / Cheng, Xiaoguang. ·Department of Radiology, Beijing Jishuitan Hospital, 4th Medical College of Peking University, Beijing, China. · Department of Radiology, University of Colorado Denver, Denver, CO, USA. · Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA. · Department of Traumatology and Orthopedic Surgery, Beijing Jishuitan Hospital, 4th Medical College of Peking University, Beijing, China. ·J Bone Miner Res · Pubmed #28407298.

ABSTRACT: There is little knowledge about the spatial distribution differences in volumetric bone mineral density and cortical bone structure at the proximal femur between femoral neck fractures and trochanteric fractures. In this case-control study, a total of 93 women with fragility hip fractures, 72 with femoral neck fractures (mean ± SD age: 70.6 ± 12.7 years) and 21 with trochanteric fractures (75.6 ± 9.3 years), and 50 control subjects (63.7 ± 7.0 years) were included for the comparisons. Differences in the spatial distributions of volumetric bone mineral density, cortical bone thickness, cortical volumetric bone mineral density, and volumetric bone mineral density in a layer adjacent to the endosteal surface were investigated using voxel-based morphometry (VBM) and surface-based statistical parametric mapping (SPM). We compared these spatial distributions between controls and both types of fracture, and between the two types of fracture. Using VBM, we found spatially heterogeneous volumetric bone mineral density differences between control subjects and subjects with hip fracture that varied by fracture type. Interestingly, femoral neck fracture subjects, but not subjects with trochanteric fracture, showed significantly lower volumetric bone mineral density in the superior aspect of the femoral neck compared with controls. Using surface-based SPM, we found that compared with controls, both fracture types showed thinner cortices in regions in agreement with the type of fracture. Most outcomes of cortical and endocortical volumetric bone mineral density comparisons were consistent with VBM results. Our results suggest: 1) that the spatial distribution of trabecular volumetric bone mineral density might play a significant role in hip fracture; 2) that focal cortical bone thinning might be more relevant in femoral neck fractures; and 3) that areas of reduced cortical and endocortical volumetric bone mineral density might be more relevant for trochanteric fractures in Chinese women. © 2017 American Society for Bone and Mineral Research.

4 Article Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study. 2019

Warden, Stuart J / Carballido-Gamio, Julio / Weatherholt, Alyssa M / Keyak, Joyce H / Yan, Chenxi / Kersh, Mariana E / Lang, Thomas F / Fuchs, Robyn K. ·Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, USA. · Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, USA. · La Trobe Sport and Exercise Medicine Research Centre, La Trobe University, Bundoora, Australia. · Department of Radiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. · Department of Kinesiology and Sport, Pott College of Science, Engineering, and Education, University of Southern Indiana, Evansville, IN, USA. · Department of Radiological Sciences, Mechanical and Aerospace Engineering, and Biomedical Engineering, University of California Irvine, Irvine, CA, USA. · Department of Mechanical Science and Engineering, College of Engineering, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL, USA. · Department of Radiology and Biomedical Imaging, School of Medicine, University of California San Francisco, San Francisco, CA, USA. ·J Bone Miner Res · Pubmed #31826314.

ABSTRACT: Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes, obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n = 16) and baseball pitchers (n = 16) were utilized as within-subject controlled models as they preferentially load their take-off leg and leg contralateral to their throwing arm, respectively. Controls (n = 15) were included but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences but less than pitchers. Pitchers had 5.8% (95% confidence interval [CI] 3.9%-7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95% CI 1.4%-6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball pitching induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (ie, fall onto the greater trochanter), raising questions as to how to better target these variables with PA. © 2019 American Society for Bone and Mineral Research.

5 Article Greater Bone Marrow Adiposity Predicts Bone Loss in Older Women. 2019

Woods, Gina N / Ewing, Susan K / Sigurdsson, Sigurdur / Kado, Deborah M / Eiriksdottir, Gudny / Gudnason, Vilmundur / Hue, Trisha F / Lang, Thomas F / Vittinghoff, Eric / Harris, Tamara B / Rosen, Clifford / Xu, Kaipin / Li, Xiaojuan / Schwartz, Ann V. ·Department of Medicine, University of California, San Diego, CA, USA. · Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA. · Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. · Icelandic Heart Association Research Institute, Kopavogur, Iceland. · Department of Family Medicine and Public Health, University of California, San Diego, CA, USA. · Faculty of Medicine, University of Iceland, Reykjavik, Iceland. · Department of Radiology & Biomedical Imaging, University of California, San Francisco, CA, USA. · National Institute on Aging, Bethesda, MD, USA. · Maine Medical Center Research Institute, Scarborough, ME, USA. · Department of Biomedical Engineering, Program of Advanced Musculoskeletal Imaging (PAMI), Cleveland Clinic, Cleveland, OH, USA. ·J Bone Miner Res · Pubmed #31618468.

ABSTRACT: Bone marrow adiposity (BMA) is associated with aging and osteoporosis, but whether BMA can predict bone loss and fractures remains unknown. Using data from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study, we investigated the associations between

6 Article Resistive exercise in astronauts on prolonged spaceflights provides partial protection against spaceflight-induced bone loss. 2019

Sibonga, J / Matsumoto, T / Jones, J / Shapiro, J / Lang, T / Shackelford, L / Smith, S M / Young, M / Keyak, J / Kohri, K / Ohshima, H / Spector, E / LeBlanc, A. ·Human Health & Performance Directorate, NASA Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058, USA. Electronic address: jean.sibonga-1@nasa.gov. · Fujii Memorial Institute of Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan. Electronic address: toshio.matsumoto@tokushima-u.ac.jp. · Center for Space Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: jajones@bcm.edu. · Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: jayrshapiro@gmail.com. · Department of Radiology, University of California, San Francisco, CA 94143, USA. Electronic address: thomas.lang@ucsf.edu. · Human Health & Performance Directorate, NASA Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058, USA. Electronic address: linda.c.shackelford@nasa.gov. · Human Health & Performance Directorate, NASA Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058, USA. Electronic address: scott.m.smith@nasa.gov. · Human Health & Performance Directorate, NASA Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058, USA. Electronic address: millennia.young@nasa.gov. · Department of Radiological Sciences, Department of Mechanical and Aerospace Engineering, Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. Electronic address: jhkeyak@uci.edu. · Department of Nephrology, Nagoya City University, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: kohri@med.nagoya-cu.ac.jp. · Japan Aerospace Exploration Agency, Tsukuba Space Center, 2-1-1 Sengen, Tsukuba-Shi, Ibaraki 305-8505, Japan. Electronic address: ohshima.hiroshi2@jaxa.jp. · KBRwyle, 2400 NASA Parkway, Houston, TX 77058, USA. Electronic address: elisabeth.r.spector@nasa.gov. · Center for Space Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: adleblanc2@gmail.com. ·Bone · Pubmed #31400472.

ABSTRACT: Bone loss in astronauts during spaceflight may be a risk factor for osteoporosis, fractures and renal stone formation. We previously reported that the bisphosphonate alendronate, combined with exercise that included an Advanced Resistive Exercise Device (ARED), can prevent or attenuate group mean declines in areal bone mineral density (aBMD) measured soon after ~ 6-month spaceflights aboard the International Space Station (ISS). It is unclear however if the beneficial effects on postflight aBMD were due to individual or combined effects of alendronate and ARED. Hence, 10 additional ISS astronauts were recruited who used the ARED (ARED group) without drug administration using similar measurements in the previous study, i.e., densitometry, biochemical assays and analysis of finite element (FE) models. In addition densitometry data (DXA and QCT only) were compared to published data from crewmembers (n = 14-18) flown prior to in-flight access to the ARED (Pre-ARED). Group mean changes from preflight (± SD %) were used to evaluate effects of countermeasures as sequentially modified on the ISS (i.e., Pre-ARED vs. ARED; ARED vs. Bis+ARED). Spaceflight durations were not significantly different between groups. Postflight bone density measurements were significantly reduced from preflight in the Pre-ARED group. As previously reported, combined Bis+ARED prevented declines in all DXA and QCT hip densitometry and in estimates of FE hip strengths; increased the aBMD of lumbar spine; and prevented elevations in urinary markers for bone resorption during spaceflight. ARED without alendronate partially attenuated declines in bone mass but did not suppress biomarkers for bone resorption or prevent trabecular bone loss. Resistive exercise in the ARED group did not prevent declines in hip trabecular vBMD, but prevented reductions in cortical vBMD of the femoral neck, in FE estimate of hip strength for non-linear stance (NLS) and in aBMD of the femoral neck. We conclude that a bisphosphonate, when combined with resistive exercise, enhances the preservation of bone mass because of the added suppression of bone resorption in trabecular bone compartment not evident with ARED alone.

7 Article Bone density and microarchitecture in hepatitis C and HIV-coinfected postmenopausal minority women. 2018

T Yin, M / RoyChoudhury, A / Nishiyama, K / Lang, T / Shah, J / Olender, S / Ferris, D C / Zeana, C / Sharma, A / Zingman, B / Bucovsky, M / Colon, I / Shane, E. ·Columbia University Medical Center, 630 w168th street, New York, NY, 10032, USA. Mty4@cumc.columbia.edu. · Cornell University Joan and Sanford I Weill Medical College, New York, NY, USA. · Columbia University Medical Center, 630 w168th street, New York, NY, 10032, USA. · University of California San Francisco, San Francisco, CA, USA. · Bronx-Lebanon Hospital Center, Bronx, NY, USA. · Montefiore, Yeshiva University Albert Einstein College of Medicine, Bronx, NY, USA. ·Osteoporos Int · Pubmed #29387910.

ABSTRACT: We found that HIV+/HCV+ women had 7-8% lower areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) at the spine, hip, and radius (p < 0.01) and 5-7% lower volumetric BMD (vBMD) by central quantitative computed tomography (cQCT) at the spine and hip (p < 0.05). These data suggest that true deficits in vBMD may contribute to bone fragility and excess fractures reported in HIV+/HCV+ women. INTRODUCTION: aBMD by DXA is lower in persons coinfected with HIV and HCV (HIV+/HCV+) than with HIV monoinfection (HIV+). However, weight is often also lower with HCV infection, and measurement of aBMD by DXA can be confounded by adiposity; we aimed to determine whether true vBMD is also lower in HIV+/HCV+ coinfection. METHODS: We measured aBMD of the lumbar spine (LS), total hip (TH), femoral neck (FN), and ultradistal radius (UDR) by DXA and vBMD of the spine and hip by cQCT and of the distal radius and tibia by high-resolution peripheral QCT (HRpQCT) in 37 HIV+/HCV+ and 119 HIV+ postmenopausal women. Groups were compared using Student's t tests with covariate adjustment by multiple regression analysis. RESULTS: HIV+/HCV+ and HIV+ women were of similar age and race/ethnicity. HIV+/HCV+ women had lower body mass index (BMI) and trunk fat and were more likely to smoke and less likely to have a history of AIDS. In HIV+/HCV+ women, aBMD by DXA was 7-8% lower at the LS, TH, and UDR (p < 0.01). Similarly, vBMD by cQCT was 5-7% lower at the LS and TH (p < 0.05). Between-group differences in LS aBMD and vBMD remained significant after adjustment for BMI, smoking, and AIDS history. Tibial total vBMD by HRpQCT was 10% lower in HIV+/HCV+ women. CONCLUSION: HIV+/HCV+ postmenopausal women had significantly lower spine aBMD and vBMD. These deficits in vBMD may contribute to bone fragility and excess fractures reported in HIV+/HCV+ women.

8 Article The comparability of HR-pQCT bone measurements is improved by scanning anatomically standardized regions. 2017

Bonaretti, S / Majumdar, S / Lang, T F / Khosla, S / Burghardt, A J. ·Musculoskeletal Quantitative Imaging Research Group, Department of Radiology & Biomedical Imaging, University of California, QB3 Building, Suite 203, 1700 4th St, San Francisco, CA, 94158, USA. · Department of Radiology, Stanford University, Stanford, CA, USA. · Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, College of Medicine, Mayo Clinic, Rochester, MN, USA. · Musculoskeletal Quantitative Imaging Research Group, Department of Radiology & Biomedical Imaging, University of California, QB3 Building, Suite 203, 1700 4th St, San Francisco, CA, 94158, USA. andrew.burghardt@ucsf.edu. ·Osteoporos Int · Pubmed #28391447.

ABSTRACT: We investigated the sensitivity of distal bone density, structure, and strength measurements by high-resolution peripheral quantitative computed tomography (HR-pQCT) to variability in limb length. Our results demonstrate that HR-pQCT should be performed at a standard %-of-total-limb-length to avoid substantial measurement bias in population study comparisons and the evaluation of individual skeletal status in a clinical context. INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone do not account for anatomic variability in bone length: a 1-cm volume is acquired at a fixed offset from an anatomic landmark. Our goal was to evaluate HR-pQCT measurement variability introduced by imaging fixed vs. proportional volumes and to propose a standard protocol for relative anatomic positioning. METHODS: Double-length (2-cm) scans were acquired in 30 adults. We compared measurements from 1-cm sub-volumes located at the default fixed offset, and the average %-of-length offset. The average position corresponded to 4.0% ± 1.1 mm for radius, and 7.2% ± 2.2 mm for tibia. We calculated the RMS difference in bone parameters and T-scores to determine the measurement variability related to differences in limb length. We used anthropometric ratios to estimate the mean limb length for published HR-pQCT reference data, and then calculated mean %-of-length offsets. RESULTS: Variability between fixed vs. relative scan positions was highest in the radius, and for cortical bone in general (RMS difference Ct.Th = 19.5%), while individuals had T-score differentials as high as +3.0 SD (radius Ct.BMD). We estimated that average scan position for published HR-pQCT reference data corresponded to 4.0% at the radius, and 7.3% at tibia. CONCLUSION: Variability in limb length introduces significant bias to HR-pQCT measures, confounding cross-sectional analyses and limiting the clinical application for individual assessment of skeletal status. We propose to standardize scan positioning using 4.0 and 7.3% of total bone length for the distal radius and tibia, respectively.

9 Article Operator variability in scan positioning is a major component of HR-pQCT precision error and is reduced by standardized training. 2017

Bonaretti, S / Vilayphiou, N / Chan, C M / Yu, A / Nishiyama, K / Liu, D / Boutroy, S / Ghasem-Zadeh, A / Boyd, S K / Chapurlat, R / McKay, H / Shane, E / Bouxsein, M L / Black, D M / Majumdar, S / Orwoll, E S / Lang, T F / Khosla, S / Burghardt, A J. ·Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA. serena.bonaretti@stanford.edu. · Department of Radiology, Stanford University, Stanford, CA, USA. serena.bonaretti@stanford.edu. · Scanco Medical AG, Brüttisellen, Switzerland. · University of California Berkeley, Berkeley, CA, USA. · Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA. · Division of Endocrinology, Department of Medicine, Columbia University Medical Center, New York, NY, USA. · University of British Columbia, Vancouver, BC, Canada. · INSERM UMR 1033, Université de Lyon, Lyon, France. · Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia. · Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. · Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, MA, USA. · Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. · Division of Endocrinology, Bone and Mineral Unit, Oregon Health & Science University, Portland, OR, USA. · Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, College of Medicine, Mayo Clinic, Rochester, MN, USA. ·Osteoporos Int · Pubmed #27475931.

ABSTRACT: In this study, we determined that operator positioning precision contributes significant measurement error in high-resolution peripheral quantitative computed tomography (HR-pQCT). Moreover, we developed software to quantify intra- and inter-operator variability and demonstrated that standard positioning training (now available as a web-based application) can significantly reduce inter-operator variability. INTRODUCTION: HR-pQCT is increasingly used to assess bone quality, fracture risk, and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection ("scout view image") and define the region to be scanned by positioning a "reference line" on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators. METHODS: To evaluate the operator in vivo measurement precision, we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner's software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled six new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group. RESULTS: In vivo precision errors were up to threefold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. The inter-operator precision errors were significantly greater than the short-term intra-operator precision (p < 0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators and lower inter-operator reproducibility (p < 0.001). Precision errors were significantly greater for the radius than for the tibia. CONCLUSION: Operator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online ( http://webapps.radiology.ucsf.edu/refline/ ).

10 Article Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2. 2016

Nielson, Carrie M / Liu, Ching-Ti / Smith, Albert V / Ackert-Bicknell, Cheryl L / Reppe, Sjur / Jakobsdottir, Johanna / Wassel, Christina / Register, Thomas C / Oei, Ling / Alonso, Nerea / Oei, Edwin H / Parimi, Neeta / Samelson, Elizabeth J / Nalls, Mike A / Zmuda, Joseph / Lang, Thomas / Bouxsein, Mary / Latourelle, Jeanne / Claussnitzer, Melina / Siggeirsdottir, Kristin / Srikanth, Priya / Lorentzen, Erik / Vandenput, Liesbeth / Langefeld, Carl / Raffield, Laura / Terry, Greg / Cox, Amanda J / Allison, Matthew A / Criqui, Michael H / Bowden, Don / Ikram, M Arfan / Mellström, Dan / Karlsson, Magnus K / Carr, John / Budoff, Matthew / Phillips, Caroline / Cupples, L Adrienne / Chou, Wen-Chi / Myers, Richard H / Ralston, Stuart H / Gautvik, Kaare M / Cawthon, Peggy M / Cummings, Steven / Karasik, David / Rivadeneira, Fernando / Gudnason, Vilmundur / Orwoll, Eric S / Harris, Tamara B / Ohlsson, Claes / Kiel, Douglas P / Hsu, Yi-Hsiang. ·School of Public Health, Oregon Health & Science University, Portland, OR, USA. · Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. · Icelandic Heart Association, Kópavogur, Iceland. · Faculty of Medicine, University of Iceland, Reykjavík, Iceland. · Department of Orthopaedics and Rehabilitation, University of Rochester, Rochester, NY, USA. · Department of Medical Biochemistry, Oslo University Hospital, Ullevål, Oslo, Norway. · Lovisenberg Diakonale Hospital, Oslo, Norway. · Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. · Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA. · Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. · Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands. · Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland, UK. · Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. · California Pacific Medical Center Research Institute, San Francisco, CA, USA. · Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, MA, USA. · National Institute on Aging (NIA), National Institutes of Health, Bethesda, MD, USA. · Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. · Department of Radiology, University of California, San Francisco (UCSF) School of Medicine, San Francisco, CA, USA. · Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Harvard University Medical School, Boston, MA, USA. · Department of Neurology, Boston University, Boston, MA, USA. · Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University Medical School, Boston, MA, USA. · Broad Institute of MIT and Harvard, Cambridge, MA, USA. · Technical University Munich, Munich, Germany. · Imaging, Icelandic Heart Association, Kópavogur, Iceland. · Department of Bioinformatics, Gothenburg University, Gothenburg, Sweden. · Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Department of Radiology & Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA. · Center for Diabetes Research, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Department of Family Medicine and Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA. · Internal Medicine/Endocrinology, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Department of Orthopaedics and Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden. · Los Angeles Biomedical Research Institute, Torrance, CA, USA. · Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland, UK. · Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. · Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel. · Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. · Division of Endocrinology, Oregon Health & Science University, Portland, OR, USA. · Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA, USA. ·J Bone Miner Res · Pubmed #27476799.

ABSTRACT: Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p = 1.9 × 10

11 Article Are bone turnover markers associated with volumetric bone density, size, and strength in older men and women? The AGES-Reykjavik study. 2016

Marques, E A / Gudnason, V / Sigurdsson, G / Lang, T / Johannesdottir, F / Siggeirsdottir, K / Launer, L / Eiriksdottir, G / Harris, T B. ·Laboratory of Epidemiology and Population Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Ave, 3C-309 Gateway Building, Bethesda, MD, 20814, USA. elisa.marques@nih.gov. · Icelandic Heart Association Research Institute, Kópavogur, Iceland. · University of Iceland, Reykjavik, Iceland. · Landspitalinn University Hospital, Reykjavik, Iceland. · Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA. · Department of Medicine, University of Cambridge, Cambridge, UK. · Laboratory of Epidemiology and Population Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Ave, 3C-309 Gateway Building, Bethesda, MD, 20814, USA. ·Osteoporos Int · Pubmed #26630978.

ABSTRACT: INTRODUCTION: The aim of this study was to examine the relationship between levels of bone turnover markers (BTMs; osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX), and procollagen type 1N propeptide (P1NP)) and quantitative computed tomography (QCT)-derived bone density, geometry, and strength indices in the lumbar spine and femoral neck (FN). METHODS: A total of 1745 older individuals (773 men and 972 women, aged 66-92 years) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort were studied. QCT was performed in the lumbar spine and hip to estimate volumetric trabecular, cortical, and integral bone mineral density (BMD), areal BMD, bone geometry, and bone strength indices. Association between BTMs and QCT variables were explored using multivariable linear regression. RESULTS: Major findings showed that all BMD measures, FN cortical index, and compressive strength had a low negative correlation with the BTM levels in both men and women. Correlations between BTMs and bone size parameters were minimal or not significant. No associations were found between BTMs and vertebral cross-sectional area in women. BTMs alone accounted for only a relatively small percentage of the bone parameter variance (1-10 %). CONCLUSION: Serum CTX, OC, and P1NP were weakly correlated with lumbar spine and FN areal and volumetric BMD and strength measures. Most of the bone size indices were not associated with BTMs; thus, the selected bone remodeling markers do not reflect periosteal bone formation. These results confirmed the limited ability of the most sensitive established BTMs to predict bone structural integrity in older adults.

12 Article Clinical Use of Quantitative Computed Tomography-Based Advanced Techniques in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part III. 2015

Engelke, Klaus / Lang, Thomas / Khosla, Sundeep / Qin, Ling / Zysset, Philippe / Leslie, William D / Shepherd, John A / Shousboe, John T. ·Institute of Medical Physics, University of Erlangen, Erlangen, Germany; Bioclinica, Hamburg, Germany. Electronic address: klaus.engelke@imp.uni-erlangen.de. · Department of Radiology and Biomedical Imaging, UCSF School of Medicine, San Francisco, CA, USA. · Center for Clinical and Translational Science, Mayo Clinic College of Medicine, Rochester, MN, USA. · Bone Quality and Health Center, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. · Institute for Surgical Technology and Biomechanics, University of Bern, Bern, Switzerland. · Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada. · Park Nicollet Clinic/HealthPartners, Minneapolis, MN, USA; Division of Health Policy and Management, University of Minnesota, Minneapolis, MN, USA. ·J Clin Densitom · Pubmed #26277853.

ABSTRACT: The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of computed tomography (CT) scans acquired without a calibration phantom, for example, CT scans obtained for other diagnosis such as colonography. This also addresses techniques suggested for opportunistic screening of osteoporosis. The ISCD task force for quantitative CT reviewed the evidence for clinical applications of these new techniques and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here we discuss the agreed upon ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Advanced techniques summarized as statistical parameter mapping methods were also reviewed. Their future use is promising but the clinical application is premature. The clinical use of QCT of the hip is addressed in part I and of finite element analysis of the hip and spine in part II.

13 Article Clinical Use of Quantitative Computed Tomography-Based Finite Element Analysis of the Hip and Spine in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part II. 2015

Zysset, Philippe / Qin, Ling / Lang, Thomas / Khosla, Sundeep / Leslie, William D / Shepherd, John A / Schousboe, John T / Engelke, Klaus. ·Institute for Surgical Technology and Biomechanics, University of Bern, Bern, Switzerland. · Bone Quality and Health Center, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. · Center for Clinical and Translational Science, Mayo Clinic College of Medicine, Rochester, MN, USA. · Department of Radiology and Biomedical Imaging, UCSF School of Medicine, San Francisco, CA, USA. · Department of Medicine, University of Manitoba, Winnipeg, Canada; Department of Radiology, University of Manitoba, Winnipeg, Canada. · Park Nicollet Clinic/HealthPartners, Minneapolis, MN, USA; Division of Health Policy and Management, University of Minnesota, Minneapolis, MN, USA. · Institute of Medical Physics, University of Erlangen, Erlangen, Germany; Bioclinica, Hamburg, Germany. Electronic address: klaus.engelke@imp.uni-erlangen.de. ·J Clin Densitom · Pubmed #26277852.

ABSTRACT: The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of quantitative computed tomography (QCT)-based finite element analysis of the spine and hip. The ISCD task force for QCT reviewed the evidence for clinical applications and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here we discuss the agreed upon ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Parts I and III address the clinical use of QCT of the hip, and the clinical feasibility of existing techniques for opportunistic screening of osteoporosis using CT scans obtained for other diagnosis such as colonography was addressed.

14 Article Clinical Use of Quantitative Computed Tomography (QCT) of the Hip in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part I. 2015

Engelke, Klaus / Lang, Thomas / Khosla, Sundeep / Qin, Ling / Zysset, Philippe / Leslie, William D / Shepherd, John A / Schousboe, John T. ·Institute of Medical Physics, University of Erlangen, Germany; Bioclinica, Hamburg, Germany. Electronic address: klaus.engelke@imp.uni-erlangen.de. · Department of Radiology and Biomedical Imaging, UCSF School of Medicine, San Francisco, CA, USA. · Center for Clinical and Translational Science, Mayo Clinic College of Medicine, Rochester, MN, USA. · Bone Quality and Health Center, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, China. · Institute for Surgical Technology & Biomechanics, University of Bern, Switzerland. · Department of Medicine, University of Manitoba, Winnipeg, Canada; Department of Radiology, University of Manitoba, Winnipeg, Canada. · Park Nicollet Clinic/HealthPartners, Minneapolis, MN, USA; Division of Health Policy and Management, University of Minnesota, Minneapolis, MN, USA. ·J Clin Densitom · Pubmed #26277851.

ABSTRACT: The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of quantitative computed tomography of the hip. The ISCD task force for quantitative computed tomography reviewed the evidence for clinical applications and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here, we discuss the agreed on ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Parts II and III address the advanced techniques of finite element analysis applied to computed tomography scans and the clinical feasibility of existing techniques for opportunistic screening of osteoporosis using computed tomography scans obtained for other diagnosis such as colonography was addressed.

15 Article Novel anthropomorphic hip phantom corrects systemic interscanner differences in proximal femoral vBMD. 2014

Bonaretti, S / Carpenter, R D / Saeed, I / Burghardt, A J / Yu, L / Bruesewitz, M / Khosla, S / Lang, T. ·Musculoskeletal Quantitative Imaging Research Group, Department of Radiology and Biomedical Imaging, University of California, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA 94107, USA. ·Phys Med Biol · Pubmed #25419618.

ABSTRACT: Quantitative computed tomography (QCT) is increasingly used in osteoporosis studies to assess volumetric bone mineral density (vBMD), bone quality and strength. However, QCT is confronted by technical issues in the clinical research setting, such as potentially confounding effects of body size on vBMD measurements and lack of standard approaches to scanner cross-calibration, which affects measurements of vBMD in multicenter settings. In this study, we addressed systematic inter-scanner differences and subject-dependent body size errors using a novel anthropomorphic hip phantom, containing a calibration hip to estimate correction equations, and a contralateral test hip to assess the quality of the correction. We scanned this phantom on four different scanners and we applied phantom-derived corrections to in vivo images of 16 postmenopausal women scanned on two scanners. From the phantom study, we found that vBMD decreased with increasing phantom size in three of four scanners and that inter-scanner variations increased with increasing phantom size. In the in vivo study, we observed that inter-scanner corrections reduced systematic inter-scanner mean vBMD differences but that the inter-scanner precision error was still larger than expected from known intra-scanner precision measurements. In conclusion, inter-scanner corrections and body size influence should be considered when measuring vBMD from QCT images.

16 Article Circulating sclerostin associated with vertebral bone marrow fat in older men but not women. 2014

Ma, Yu-Heng Vivian / Schwartz, Ann V / Sigurdsson, Sigurdur / Hue, Trisha F / Lang, Thomas F / Harris, Tamara B / Rosen, Clifford J / Vittinghoff, Eric / Eiriksdottir, Gudny / Hauksdottir, Alda M / Siggeirsdottir, Kristin / Sigurdsson, Gunnar / Oskarsdottir, Diana / Napoli, Nicola / Palermo, Lisa / Gudnason, Vilmundur / Li, Xiaojuan. ·University of California, San Francisco (Y.-H.V.M., A.V.S., T.F.H., T.F.L., E.V., L.P., X.L.), San Francisco, California 94107 · Icelandic Heart Association (S.S., G.E., A.M.H., K.S., D.O., V.G.), IS-201 Kopavogur, Iceland · Laboratory of Epidemiology, Demography, and Biometry (T.B.H.), Intramural Research Program, National Institute on Aging, Bethesda, Maryland 20892 · Maine Medical Center Research Institute (C.J.R.), Scarborough, Maine 04074 · Faculty of Medicine (G.S., D.O., V.G.), University of Iceland, IS-101 Reykjavik, Iceland · Department of Endocrinology and Metabolism (G.S.), Landspitali University Hospital, IS-101 Reykjavik, Iceland · and Universita Campus Bio-Medico (N.N.), 00128 Rome, Italy. ·J Clin Endocrinol Metab · Pubmed #25144629.

ABSTRACT: CONTEXT: Osteocyte activity is crucial to the maintenance of bone quality. Sclerostin, an osteocyte product, inhibits bone formation, yet higher circulating sclerostin is associated with higher bone density. Bone marrow fat (MF) is associated with osteoporosis, but little is known about the relationship between osteocyte activity and MF. OBJECTIVE: Our objective was to assess the relationships between circulating sclerostin, vertebral MF, volumetric bone mineral density (vBMD), and other fat depots in older adults. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional study in the Age Gene/Environment Susceptibility-Reykjavik cohort. MAIN OUTCOME MEASURES: Outcome measures included vertebral MF (L1-L4) measured with magnetic resonance spectroscopy and vBMD (spine and hip) and abdominal fat measured with quantitative computed tomography. RESULTS: After excluding subjects with bone-active medication use (n = 50), inadequate serum (n = 2), or inadequate magnetic resonance spectroscopy (n = 1), analyses included 115 men and 134 women (mean age 79 y, mean body mass index 27.7 kg/m(2)). In men, but not women, vertebral MF was greater in those with higher serum sclerostin levels. MF was 52.2 % in the lowest tertile of serum sclerostin and 56.3% in the highest tertile in men (P for trend <.01) in models adjusted for age, body mass index, and diabetes. Sclerostin was positively associated with cortical and trabecular total hip vBMD, weight in men and women, and total fat mass in men but was not associated with total lean mass or abdominal fat depots. CONCLUSION: Circulating sclerostin levels are associated with higher vertebral marrow fat in men, suggesting a relationship between osteocyte function and marrow adipogenesis.

17 Article Structural patterns of the proximal femur in relation to age and hip fracture risk in women. 2013

Carballido-Gamio, Julio / Harnish, Roy / Saeed, Isra / Streeper, Timothy / Sigurdsson, Sigurdur / Amin, Shreyasee / Atkinson, Elizabeth J / Therneau, Terry M / Siggeirsdottir, Kristin / Cheng, Xiaoguang / Melton, L Joseph / Keyak, Joyce H / Gudnason, Vilmundur / Khosla, Sundeep / Harris, Tamara B / Lang, Thomas F. ·Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA. ·Bone · Pubmed #23981658.

ABSTRACT: Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21-97years) was included in this study, along with a cohort of 222 older women (mean age 79±7years) with (n=74) and without (n=148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Student's t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction.

18 Article Effect of finite element model loading condition on fracture risk assessment in men and women: the AGES-Reykjavik study. 2013

Keyak, J H / Sigurdsson, S / Karlsdottir, G S / Oskarsdottir, D / Sigmarsdottir, A / Kornak, J / Harris, T B / Sigurdsson, G / Jonsson, B Y / Siggeirsdottir, K / Eiriksdottir, G / Gudnason, V / Lang, T F. ·Department of Radiological Sciences, University of California, Irvine, CA, USA; Department of Biomedical Engineering, University of California, Irvine, CA, USA; Department of Mechanical and Aerospace Engineering, University of California, Irvine, CA, USA. Electronic address: jhkeyak@uci.edu. ·Bone · Pubmed #23907032.

ABSTRACT: Proximal femoral (hip) strength computed by subject-specific CT scan-based finite element (FE) models has been explored as an improved measure for identifying subjects at risk of hip fracture. However, to our knowledge, no published study has reported the effect of loading condition on the association between incident hip fracture and hip strength. In the present study, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Baseline (pre-fracture) quantitative CT (QCT) scans of 5500 older male and female subjects were obtained. During 4-7years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as controls from a pool of age- and sex-matched subjects. From the QCT data, FE models employing nonlinear material properties computed FE-strength of the left hip of each subject in loading from a fall onto the posterolateral (FPL), posterior (FP) and lateral (FL) aspects of the greater trochanter (patent pending). For comparison, FE strength in stance loading (FStance) and total femur areal bone mineral density (aBMD) were also computed. For all loading conditions, the reductions in strength associated with fracture in men were more than twice those in women (p≤0.01). For fall loading specifically, posterolateral loading in men and posterior loading in women were most strongly associated with incident hip fracture. After adjusting for aBMD, the association between FP and fracture in women fell short of statistical significance (p=0.08), indicating that FE strength provides little advantage over aBMD for identifying female hip fracture subjects. However, in men, after controlling for aBMD, FPL was 424N (11%) less in subjects with fractures than in controls (p=0.003). Thus, in men, FE models of posterolateral loading include information about incident hip fracture beyond that in aBMD.

19 Article Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight. 2013

Leblanc, A / Matsumoto, T / Jones, J / Shapiro, J / Lang, T / Shackelford, L / Smith, S M / Evans, H / Spector, E / Ploutz-Snyder, R / Sibonga, J / Keyak, J / Nakamura, T / Kohri, K / Ohshima, H. ·Universities Space Research Association, 3600 Bay Area Blvd, Houston, TX 77058, USA. leblanc@dsls.usra.edu ·Osteoporos Int · Pubmed #23334732.

ABSTRACT: INTRODUCTION: This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long-duration spaceflight. METHODS: We report the results from seven International Space Station (ISS) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission. All crewmembers had available for exercise a treadmill, cycle ergometer, and a resistance exercise device. Our assessment included densitometry of multiple bone regions using X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and assays of biomarkers of bone metabolism. RESULTS: In addition to pre- and post-flight measurements, we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device, called the interim resistance exercise device, and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device (ARED). Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained. The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including: DXA-determined losses in bone mineral density of the spine, hip, and pelvis, QCT-determined compartmental losses in trabecular and cortical bone mass in the hip, calculated measures of fall and stance computed bone strength of the hip, elevated levels of bone resorption markers, and urinary excretion of calcium. CONCLUSIONS: The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long-duration spaceflight.

20 Article Central QCT reveals lower volumetric BMD and stiffness in premenopausal women with idiopathic osteoporosis, regardless of fracture history. 2012

Cohen, Adi / Lang, Thomas F / McMahon, Donald J / Liu, X Sherry / Guo, X Edward / Zhang, Chiyuan / Stein, Emily M / Dempster, David W / Young, Polly / Saeed, Isra / Lappe, Joan M / Recker, Robert R / Shane, Elizabeth. ·Department of Medicine, PH8-864, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA. ac1044@columbia.edu ·J Clin Endocrinol Metab · Pubmed #22962425.

ABSTRACT: CONTEXT: Idiopathic osteoporosis (IOP) affects otherwise healthy young individuals with intact gonadal function and no secondary cause of bone fragility. In premenopausal women with IOP, a low trauma fracture is evidence of impaired bone quality and strength. The extent to which low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) reflects low volumetric BMD, bone microstructure, and strength is uncertain in the absence of low trauma fracture. OBJECTIVE: The objective of the study was to compare three-dimensional volumetric BMD and bone stiffness in premenopausal women with IOP based on fracture history, those with idiopathic low BMD (Z score ≤ -2.0) and no low trauma fracture, and normal age-matched controls. DESIGN: We measured volumetric BMD and bone geometry by central quantitative computed tomography (cQCT) scans of the spine and hip and estimated bone stiffness by finite element analysis of cQCT data sets in 32 premenopausal women with IOP, 12 with idiopathic low BMD, and 34 controls. RESULTS: Subjects had comparable decreases in total and trabecular volumetric BMD, cortical thickness, and whole-bone stiffness compared with controls, regardless of fracture history. These differences remained significant after controlling for age, body mass index, and bone size. The positive predictive values of a DXA Z score of -2.0 or less for a cQCT volumetric BMD Z score of -2.0 or less were 95% at the lumbar spine, 90% at the total hip, and 86% at the femoral neck. CONCLUSION: Women with idiopathic low BMD alone and those with low trauma fractures had comparable deficits in bone mass, structure, and stiffness. Low areal BMD by DXA is fairly accurate for predicting low volumetric BMD by cQCT. These results are consistent with three-dimensional bone imaging at the iliac crest, radius, and tibia in premenopausal IOP and suggest that the term osteoporosis may be appropriate in women with Z scores below -2.0, whether or not there is a history of fracture.

21 Article A statistical method (cross-validation) for bone loss region detection after spaceflight. 2010

Zhao, Qian / Li, Wenjun / Li, Caixia / Chu, Philip W / Kornak, John / Lang, Thomas F / Fang, Jiqian / Lu, Ying. ·Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China. ·Australas Phys Eng Sci Med · Pubmed #20632144.

ABSTRACT: Astronauts experience bone loss after the long spaceflight missions. Identifying specific regions that undergo the greatest losses (e.g. the proximal femur) could reveal information about the processes of bone loss in disuse and disease. Methods for detecting such regions, however, remains an open problem. This paper focuses on statistical methods to detect such regions. We perform statistical parametric mapping to get t-maps of changes in images, and propose a new cross-validation method to select an optimum suprathreshold for forming clusters of pixels. Once these candidate clusters are formed, we use permutation testing of longitudinal labels to derive significant changes.

22 Article Insights from the conduct of a device trial in older persons: low magnitude mechanical stimulation for musculoskeletal health. 2010

Kiel, Douglas P / Hannan, Marian T / Barton, Bruce A / Bouxsein, Mary L / Lang, Thomas F / Brown, Kathleen M / Shane, Elizabeth / Magaziner, Jay / Zimmerman, Sheryl / Rubin, Clinton T. ·Institute for Aging Research, Boston, MA, USA. kiel@hrca.harvard.edu ·Clin Trials · Pubmed #20571129.

ABSTRACT: BACKGROUND: Osteoporosis is a common complication of aging. Alternatives to pharmacologic treatment are needed for older adults. Nonpharmacologic treatment with low magnitude, high frequency mechanical stimulation has been shown to prevent bone loss in animal and human studies. METHODS: The VIBES (Vibration to Improve Bone Density in Elderly Subjects) study is a randomized, double-blind, sham-controlled trial of the efficacy of low magnitude, high frequency mechanical stimulation in 200 men and women aged 60 years and older with bone mineral density T-scores by dual X-ray absorptiometry between -1 and -2.5 at entry. Participants are healthy, cognitively intact residents of independent living communities in the Boston area who receive free calcium and Vitamin D supplements. They are randomly assigned to active or sham treatment and stand on their assigned platform once daily for 10 min. All platforms have adherence data collection software downloadable to a laptop computer. Adverse events are closely monitored. 174 participants were randomized and will be followed for 2 years. Almost all active subjects have attained 1 year of follow-up. Bone mineral density is measured by both dual X-ray absorptiometry and quantitative computed tomography at baseline and annually. The main analysis will compare mean changes from baseline in volumetric bone density by quantitative computed tomography in active and sham groups. Adherence and treatment effect magnitude will also be evaluated. Secondary analyses will compare changes in two biochemical markers of bone turnover as well as longitudinal comparisons of muscle and balance endpoints. RESULTS: The VIBES trial has completed its first year of data collection and encountered multiple challenges leading to valuable lessons learned about the areas of recruitment from independent living communities, deployment of multiuser mechanical devices using radio frequency identification cards and electronic adherence monitoring, organization of transportation for imaging at a central site, and the expansion of study aims to include additional musculoskeletal outcomes. CONCLUSIONS: These lessons will guide future investigations in studies of individuals of advanced age.