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Timothy C R Prickett
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Graham K Barrell Department of Medicine, Agriculture & Life Sciences Division, University of Otago, PO Box 4345, Christchurch 8140, New Zealand

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Martin Wellby Department of Medicine, Agriculture & Life Sciences Division, University of Otago, PO Box 4345, Christchurch 8140, New Zealand

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Timothy G Yandle
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A Mark Richards
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Eric A Espiner
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. 2005 ) and is readily measurable in plasma ( Prickett et al . 2001 ) has opened up new approaches to assessing CNP's paracrine actions and role in skeletal biology. For example, the plasma concentration of NTproCNP and markers of bone formation

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F Labrie Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Québec G1 V 4 G2, Canada

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V Luu-The Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Québec G1 V 4 G2, Canada

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A Bélanger Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Québec G1 V 4 G2, Canada

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S-X Lin Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Québec G1 V 4 G2, Canada

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J Simard Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Québec G1 V 4 G2, Canada

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G Pelletier Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Québec G1 V 4 G2, Canada

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C Labrie Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Québec G1 V 4 G2, Canada

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study has been attributed to the different routes of administration of the estrogen, the cause of the difference could well be the action of testosterone. As an index of increased bone formation, an increase in serum osteocalcin, a marker of bone

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Iris Boraschi-Diaz Shriners Hospital for Children-Canada, Montreal, Quebec, Canada
Faculty of Dentistry, McGill University, Montreal, Quebec, Canada

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Josephine T Tauer Shriners Hospital for Children-Canada, Montreal, Quebec, Canada

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Omar El-Rifai Unité de Recherche en Physiologie Intégrative et Moléculaire, Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada

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Delphine Guillemette Shriners Hospital for Children-Canada, Montreal, Quebec, Canada
Département de Mathématiques, Université du Québec à Montréal, Montréal, Québec, Canada

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Geneviève Lefebvre Département de Mathématiques, Université du Québec à Montréal, Montréal, Québec, Canada

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Frank Rauch Shriners Hospital for Children-Canada, Montreal, Quebec, Canada

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Mathieu Ferron Unité de Recherche en Physiologie Intégrative et Moléculaire, Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada
Départements de Médecine et de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, Québec, Canada

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Svetlana V Komarova Shriners Hospital for Children-Canada, Montreal, Quebec, Canada
Faculty of Dentistry, McGill University, Montreal, Quebec, Canada

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oxidation in muscle cells ( Mera et al . 2016 ). Bone histomorphometric studies have shown that children and adolescents with OI have increased rates of bone formation and resorption ( Rauch et al . 2000 , 2010 ). Similarly, several mouse models of OI

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Shan-Jin Wang Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China

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Xin-Feng Li Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China

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Lei-Sheng Jiang Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China

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Li-Yang Dai Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China

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Introduction The development of bones is a result of endochondral bone formation that occurs at the epiphyseal growth plate through a process whereby cartilage is formed and then remodeled into bone tissue. This complex process is regulated by

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Nabanita S Datta Division of Endocrinology, Department of Internal Medicine, Wayne State University School of Medicine, 1107 Elliman Building, 421 East Canfield Avenue, Detroit, Michigan 48201, USA

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Tareq A Samra Division of Endocrinology, Department of Internal Medicine, Wayne State University School of Medicine, 1107 Elliman Building, 421 East Canfield Avenue, Detroit, Michigan 48201, USA

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Chandrika D Mahalingam Division of Endocrinology, Department of Internal Medicine, Wayne State University School of Medicine, 1107 Elliman Building, 421 East Canfield Avenue, Detroit, Michigan 48201, USA

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Tanuka Datta Division of Endocrinology, Department of Internal Medicine, Wayne State University School of Medicine, 1107 Elliman Building, 421 East Canfield Avenue, Detroit, Michigan 48201, USA

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Abdul B Abou-Samra Division of Endocrinology, Department of Internal Medicine, Wayne State University School of Medicine, 1107 Elliman Building, 421 East Canfield Avenue, Detroit, Michigan 48201, USA

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mechanisms affecting bone formation and resorption in the vertebrae and the femur are likely to be different. PTH stimulates PTH1R to increase intracellular cAMP, which in turn activates PKA leading to phosphorylation of the cAMP-response element

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Victoria E DeMambro
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Masanobu Kawai The Jackson Laboratory, Medical Center Research Institute, John Hopkins University, Massachusetts General Hospital, Department of Research, 600 Main Street, Bar Harbor, Maine 04609, USA

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Thomas L Clemens The Jackson Laboratory, Medical Center Research Institute, John Hopkins University, Massachusetts General Hospital, Department of Research, 600 Main Street, Bar Harbor, Maine 04609, USA

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Keertik Fulzele The Jackson Laboratory, Medical Center Research Institute, John Hopkins University, Massachusetts General Hospital, Department of Research, 600 Main Street, Bar Harbor, Maine 04609, USA

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Jane A Maynard
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Caralina Marín de Evsikova
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Kenneth R Johnson
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Ernesto Canalis The Jackson Laboratory, Medical Center Research Institute, John Hopkins University, Massachusetts General Hospital, Department of Research, 600 Main Street, Bar Harbor, Maine 04609, USA

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Wesley G Beamer
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Clifford J Rosen The Jackson Laboratory, Medical Center Research Institute, John Hopkins University, Massachusetts General Hospital, Department of Research, 600 Main Street, Bar Harbor, Maine 04609, USA

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Leah Rae Donahue
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development. For example, global Igf1 gene deletion causes a dramatic skeletal phenotype characterized by impaired bone formation and bone resorption ( Liu et al . 1993 , Bikle et al . 2001 , He et al . 2006 , Wang et al . 2006 ). Conditional targeted

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Anna E Bollag Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Tianyang Guo Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Ke-Hong Ding Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Vivek Choudhary Charlie Norwood VA Medical Center, Augusta, Georgia, USA
Department of Physiology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Xunsheng Chen Charlie Norwood VA Medical Center, Augusta, Georgia, USA
Department of Physiology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Qing Zhong Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Jianrui Xu Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Kanglun Yu Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Mohamed E Awad Department of Oral Biology, Dental College of Georgia at Augusta University, Augusta, Georgia, USA

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Mohammed Elsalanty Department of Oral Biology, Dental College of Georgia at Augusta University, Augusta, Georgia, USA

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Maribeth H Johnson Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Meghan E McGee-Lawrence Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia, USA
Department of Orthopaedic Surgery, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Wendy B Bollag Charlie Norwood VA Medical Center, Augusta, Georgia, USA
Department of Physiology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA
Department of Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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Carlos M Isales Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA
Department of Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

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known to activate multiple transcription factors important in bone formation ( Kanczler et al. 1998 ). The importance of oxidants as signaling molecules suggests, therefore, that global inhibition of oxidation with antioxidant supplementation might

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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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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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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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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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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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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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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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(hPTH1–84) secretion, decreased bone formation and increased bone-resorption markers ( Cosman et al. 1991 ). Chen et al. (2003) compared bone mass and structure among patients with hyper- and hypoparathyroidism and control subjects by dual-energy X

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J H Tobias
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A Gallagher
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T J Chambers
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Abstract

Although short-term administration of oestradiol-17β (OE2) stimulates cancellous bone formation in the rat, this is replaced by a tendency to suppression after prolonged treatment. Hence, in rats rendered osteopaenic by ovariectomy, OE2 administration fails either to induce a sustained increase in bone formation or to restore bone volume. A possible explanation for this failure is that OE2 also inhibits bone resorption, secondarily suppressing bone formation through coupling mechanisms. We therefore investigated whether the effects of OE2 treatment might be modified by intermittently stimulating bone resorption with retinoic acid (120mg/kg daily) for 4 out of every 20 days. We found, in a preliminary experiment using intact animals, that intermittent retinoic acid reduced cancellous bone volume, consistent with previously documented stimulation of bone resorption by retinoic acid. Rats were then rendered osteopaenic by ovariectomy, and given vehicle, retinoic acid and/or OE2. We found that animals treated with intermittent retinoic acid and OE2 showed a substantial increase in cancellous bone volume compared with ovariectomized animals treated with vehicle, retinoic acid alone or OE2 alone. Therefore, intermittent retinoic acid appears to cause a net increase in bone formation over resorption when given to ovariectomized animals in conjunction with OE2. We conclude that the effects of OE2 on cancellous bone are modified by intermittent treatment with retinoic acid, resulting in a substantial increase in bone volume.

Journal of Endocrinology (1994) 142, 61–67

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M. HARRISON
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RUSSELL FRASER
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SUMMARY

1. The retention of a dose of stable strontium given intraperitoneally to rats has been measured after 24 hr.

2. When the total retention is expressed in terms of the amount in the plasma, it provides an estimate of the rate of bone formation.

3. The strontium retention is a function of the age of the rat, but is independent of the sex.

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