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Russell T Turner Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences
Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences

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Kenneth A Philbrick Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences

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Carmen P Wong Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences

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Dawn A Olson Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences

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Adam J Branscum Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences

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Urszula T Iwaniec Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences
Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences

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Leptin-deficient ob/ob mice are morbidly obese and exhibit low total bone mass and mild osteopetrosis. In order to disassociate the skeletal effects of leptin deficiency from those associated with morbid obesity, we evaluated bone mass, architecture, gene expression, and indices of bone turnover in WT mice, ob/ob mice allowed to feed ad libitum (ob/ob), and ob/ob mice pair-fed equivalent to WT mice (pair-fed ob/ob). Mice were maintained at 32 °C (thermoneutral) from 6 to 18 weeks of age to minimize differences in resting energy expenditure. ob/ob mice were heavier, had more abdominal white adipose tissue (WAT), and were hyperglycemic compared with WT mice. Femur length, bone mineral content (BMC) and bone mineral density, and midshaft femur cortical thickness were lower in ob/ob mice than in WT mice. Cancellous bone volume (BV) fraction was higher but indices of bone formation and resorption were lower in ob/ob mice compared with WT mice; reduced bone resorption in ob/ob mice resulted in pathological retention of calcified cartilage. Pair-fed ob/ob mice were lighter and had lower WAT, uterine weight, and serum glucose than ob/ob mice. Similarly, femoral length, BMC, and cortical thickness were lower in pair-fed ob/ob mice compared with ob/ob mice, as were indices of cancellous bone formation and resorption. In contrast, bone marrow adiposity, calcified cartilage, and cancellous BV fraction were higher at one or more cancellous sites in pair-fed ob/ob mice compared with ob/ob mice. These findings indicate that the skeletal abnormalities caused by leptin deficiency are markedly attenuated in morbidly obese ob/ob mice.

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F González Department of Reproductive Biology and
Department of Medicine, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, USA

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N S Rote Department of Reproductive Biology and
Department of Medicine, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, USA

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J Minium Department of Reproductive Biology and
Department of Medicine, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, USA

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J P Kirwan Department of Reproductive Biology and
Department of Medicine, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, USA

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and used to estimate abdominal adiposity ( Kohrt et al. 1993 ). In addition, all subjects underwent dual energy absorptiometry (DEXA) to determine percent total body fat and percent truncal fat with the QDR 4500 Elite model scanner (Hologic, Waltham

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Russell T Turner Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA
Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon, USA

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Kenneth A Philbrick Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA

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Amida F Kuah Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA

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Adam J Branscum Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA

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Urszula T Iwaniec Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA
Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon, USA

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vertebrae were removed, fixed for 24h in 10% buffered formalin and stored in 70% ethanol for dual energy absorptiometry (DXA), microcomputed tomography (µCT) and histomorphometric analyses. The experimental protocol was approved by the Institutional Animal

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Russell T Turner Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA
Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Michael Dube Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Adam J Branscum Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Carmen P Wong Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Dawn A Olson Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Xiaoying Zhong Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Mercedes F Kweh Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Iske V Larkin Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Thomas J Wronski Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Clifford J Rosen Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Satya P Kalra Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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Urszula T Iwaniec Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA
Skeletal Biology Laboratory, Center for Healthy Aging Research, Department of Neuroscience, Biostatistics, Department of Physiological Sciences, Department of Large Animal Clinical Sciences, Maine Medical Center Research Institute, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA

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ribosomal RNA gene. Dual Energy X-ray absorptiometry Total femur bone mineral content (BMC, g), area (cm 2 ), and bone mineral density (BMD, g/cm 2 ) were measured ex vivo using dual energy absorptiometry (DXA; Piximus 2, Lunar Corp., Madison, WI, USA

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Urszula T Iwaniec Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA
Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon, USA

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Russell T Turner Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA
Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon, USA

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. An important unanswered question is whether bone mass and quality is appropriate for adult-associated weight gain. Several methods have been used to adjust BMD for differences in body size in children and adults. In children, dual-energy

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