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Russell T Turner
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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Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences
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Kenneth A Philbrick
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
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
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
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
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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Skeletal Biology Laboratory, Center for Healthy Aging Research, Biostatistics, School of Biological and Population Health Sciences
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dual-energy X-ray absorptiometry (DXA), microcomputed tomography (μCT), and histomorphometry. Tibiae were removed, cleaned of soft tissue, frozen in liquid nitrogen, and stored at −80 °C for mRNA isolation and gene expression analysis. Serum chemistry
Russell T Turner
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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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
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
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
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
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
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
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
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
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
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
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
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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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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). Microcomputed tomography Microcomputed tomography (μCT) was used for nondestructive high resolution 3-dimensional evaluation of cortical and cancellous bone volume and architecture. Midshaft and distal femora and 2nd lumbar vertebrae were scanned in 70% ethanol
Guillaume Mabilleau
Guillaume Mabilleau
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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Aleksandra Mieczkowska
Aleksandra Mieczkowska
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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Nigel Irwin
Nigel Irwin
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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Peter R Flatt
Peter R Flatt
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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Daniel Chappard
Daniel Chappard
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM) – LHEA, Service Commun d'Imageries
et d'Analyses Microscopiques (SCIAM), School of Biomedical Sciences
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-ray microcomputed tomography X-ray microcomputed tomography (micro-CT) analysis was performed in the proximal left femur with a Skyscan 1172 microtomograph (Bruker Micro-CT, Kontich, Belgium) equipped with an X-ray tube working at 69 kV/100 μA. The pixel size was
Russell T Turner
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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Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon, USA
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Kenneth A Philbrick
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
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
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
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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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
M J Devlin
M J Devlin
Department of Anthropology, University of Michigan, Ann Arbor, Michigan, USA
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D J Brooks
D J Brooks
Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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C Conlon
C Conlon
Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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M van Vliet
M van Vliet
Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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L Louis
L Louis
Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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C J Rosen
C J Rosen
Maine Medical Center Research Institute, Scarborough, Maine, USA
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M L Bouxsein
M L Bouxsein
Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA
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Harvard Medical School, Boston, Massachusetts, USA
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right tibia was fixed in 10% neutral buffered formalin at 4°C overnight and stored in PBS for osmium tetroxide staining ( Scheller et al . 2014 ). Trabecular and cortical bone morphology by microcomputed tomography Bone microarchitecture of the
Chandrika D Mahalingam
Chandrika D Mahalingam
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Tanuka Datta
Tanuka Datta
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Rashmi V Patil
Rashmi V Patil
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Jaclynn Kreider
Jaclynn Kreider
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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R Daniel Bonfil
R Daniel Bonfil
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Keith L Kirkwood
Keith L Kirkwood
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Steven A Goldstein
Steven A Goldstein
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Abdul B Abou-Samra
Abdul B Abou-Samra
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Nabanita S Datta
Nabanita S Datta
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
Division of Endocrinology, Department of Orthopedic Surgery, Department of Urology and Pathology, Departments of Craniofacial Biology and Microbiology and Immunology, Barbara Ann Karmanos Cancer Institute, Cardiovascular Research Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
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the last injection, and bone tissues were collected. Skeletal phenotyping, and microcomputed tomography analysis Femora and tibiae were dissected free of soft tissue, fixed in 10% neutral buffered formalin for 48 h, and analyzed by microcomputed
M J Devlin
M J Devlin
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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C Grasemann
C Grasemann
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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A M Cloutier
A M Cloutier
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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L Louis
L Louis
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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C Alm
C Alm
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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M R Palmert
M R Palmert
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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M L Bouxsein
M L Bouxsein
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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Beth Israel Deaconess Medical Center, Harvard Medical School, Hospital for Sick Children, The University of Toronto, Kinderklinik UK‐Essen, The University of Duisburg‐Essen, Department of Anthropology, University of Michigan, Boston, Massachusetts, USA
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by microcomputed tomography Assessment of bone morphology and microarchitecture was performed with high-resolution microcomputed tomography (μCT40, Scanco Medical, Brüttisellen, Switzerland) of the distal femoral metaphysis and L5 vertebral body, as
Rosa Chung
Rosa Chung
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Bruce K Foster
Bruce K Foster
School of Pharmacy and Medical Sciences, Department of Orthopaedic Surgery, Sansom Institute for Health Research, University of South Australia, City East Campus, GPO Box 2471, Adelaide, South Australia 5001, Australia
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Cory J Xian
Cory J Xian
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24 h at 4 °C and then wrapped in saline-soaked gauze and frozen at −80 °C until use for microcomputed tomography (microCT) analysis (see below). Following microCT scans, bones were immediately decalcified for 14 days in Immunocal solution (Decal
Saranyapin Potikanond
Saranyapin Potikanond
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Pinyada Rattanachote
Pinyada Rattanachote
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Hiranya Pintana
Hiranya Pintana
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Panan Suntornsaratoon
Panan Suntornsaratoon
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Narattaphol Charoenphandhu
Narattaphol Charoenphandhu
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Nipon Chattipakorn
Nipon Chattipakorn
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Siriporn Chattipakorn
Siriporn Chattipakorn
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Department of Pharmacology, Neurophysiology Unit, Center of Calcium and Bone Research (COCAB), Department of Physiology, Cardiac Electrophysiology Unit, Center of Excellence in Cardiac Electrophysiology Research, Department of Oral Biology and Diagnostic Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, n=12) or a sham operation (S, n=12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats.
A Iida-Klein
A Iida-Klein
Regional Bone and
Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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S Shou Lu
S Shou Lu
Regional Bone and
Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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R Kapadia
R Kapadia
Regional Bone and
Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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M Burkhart
M Burkhart
Regional Bone and
Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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A Moreno
A Moreno
Regional Bone and
Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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D W Dempster
D W Dempster
Regional Bone and
Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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R Lindsay
R Lindsay
Regional Bone and
Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
Scanco USA Inc., Wayne, Pennsylvania, USA
Departments of Clinical Pathology and
Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Parathyroid hormone (PTH) stimulates bone resorption as well as bone formation in vivo and in organ culture. The catabolic actions of PTH have been recognized in patients with hyperparathyroidism, or with acute infusion of the N-terminal 1–34 fragment of human PTH (hPTH1–34). Whereas the anabolic actions of daily injection with PTH have been well studied in both humans and mice, the catabolic actions of PTH on murine bone remain to be defined. To do this we sought to create a model with short-term, sustained hyperparathyroidism using osmotic infusion pumps. We treated 10-week-old female C57BL/J6 mice with continuous infusion of hPTH1–34 (8.1 pmol/0.25 μl per h, equivalent to 40 μg/kg per day) or vehicle for 2 weeks, using Alzet osmotic pumps. Bone mineral density (BMD), serum total calcium, hPTH1–34, mouse intact PTH (mPTH1–84), osteocalcin and mouse tartrate-resistant acid phosphatase (mTRAP) activity, and microarchitectural variables of the distal femur were measured. Separately, we compared the effects of intermittent daily injection of hPTH1–34 (40 μg/kg per day) with continuous infusion of hPTH1–34 on BMD and bone markers. Exogenous hPTH1–34 was detected only in the PTH-infused mice. Both intermittent and continuous treatment with hPTH1–34 markedly suppressed endogenous mPTH1–84, but only the latter induced hypercalcemia. Daily PTH injection significantly increased both serum osteocalcin and mTRAP, while continuous PTH infusion showed a strong trend to stimulate mTRAP, with a slight but non-significant increase in osteocalcin. There were significant differences in BMD at all sites between animals treated with the same daily dose of intermittent and continuous hPTH1–34. Microcomputed tomography (μCT) analysis of the distal femurs revealed that hPTH1–34 infusion significantly decreased trabecular connectivity density (P<0.05). Thus, the murine bone response to continuous PTH infusion was quite different from that seen with daily PTH injection. Short-term infusion of hPTH1–34 appears to be a good model to study the mechanisms underlying the catabolic action of PTH in mice.
