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R Dobie
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V E MacRae
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C Huesa
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R van't Hof Division of Developmental Biology, Institute of Ageing and Chronic Disease, Developmental Endocrinology Research Group, The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, Scotland, UK

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S F Ahmed Division of Developmental Biology, Institute of Ageing and Chronic Disease, Developmental Endocrinology Research Group, The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, Scotland, UK

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C Farquharson
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Roith et al . 2001 ). The intimate relationship between GH and IGF1 makes it difficult to deduce the relative contributions of systemic and locally derived IGF1 to bone accrual. While Ghr −/− mice have recognised changes in skeletal mass and

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Bernard Freudenthal Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK

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John Logan Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK

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Sanger Institute Mouse Pipelines Mouse Pipelines, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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Peter I Croucher Garvan Institute of Medical Research, Sydney, New South Wales, Australia

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Graham R Williams Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK

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J H Duncan Bassett Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK

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al . 2009 ). The most important risk factors for osteoporotic fracture are low bone mineral density (BMD) (clinically assessed by dual-energy X-ray absorptiometry (DEXA or DXA)), increasing age and history of fracture ( Johnell et al . 2005

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K A Staines
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A S Pollard
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I M McGonnell
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C Farquharson Comparative Biomedical Sciences, Roslin Institute and R(D)SVS, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK

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A A Pitsillides
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Introduction The transition of cartilage to bone is the basis by which all long bones form. This transition is tightly regulated to ensure both permissive foetal development through endochondral ossification and postnatal longitudinal growth at the

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Carmen Corciulo Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Julia M Scheffler Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Piotr Humeniuk Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Alicia Del Carpio Pons Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Alexandra Stubelius Division of Chemical Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

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Ula Von Mentzer Division of Chemical Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

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Christina Drevinge Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Aidan Barrett Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Sofia Wüstenhagen Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Matti Poutanen Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Turku, Finland

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Claes Ohlsson Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Department of Drug Treatment, Sahlgrenska University Hospital, Gothenburg, Sweden

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Marie K Lagerquist Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Ulrika Islander Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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associated with structural subchondral bone damage, increased pain sensitivity also in body parts that are not directly affected by the disease, and mild inflammation of the synovium ( Loeser et al. 2012 ). OA affects more than 240 million people globally

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Andrea Lovdel University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Karla J Suchacki University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Fiona Roberts University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Richard J Sulston University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Robert J Wallace Department of Orthopaedics, The University of Edinburgh, Edinburgh, UK

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Benjamin J Thomas University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Rachel M B Bell University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Iris Pruñonosa Cervera University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Gavin J Macpherson Department of Orthopaedic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK

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Nicholas M Morton University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK
Centre for Systems Health and Integrated Metabolic Research, Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, UK

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Natalie Z M Homer University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Karen E Chapman University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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William P Cawthorn University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK

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Introduction Bone marrow adipocytes comprise up to 70% of total bone marrow (BM) volume and over 10% of total adipose mass in healthy adult humans, collectively forming an integrated tissue referred to as bone marrow adipose tissue (BMAT

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Karin L Gustafsson Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Sofia Movérare-Skrtic Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Helen H Farman Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Cecilia Engdahl Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Petra Henning Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Karin H Nilsson Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Julia M Scheffler Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Edina Sehic Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Ulrika Islander Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Ellis Levin Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, California, USA
Department of Veterans Affairs Medical Center, Long Beach, Long Beach, California, USA

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Claes Ohlsson Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden

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Marie K Lagerquist Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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-generation SERMs, have agonistic effects in bone and can prevent both vertebral and non-vertebral fractures in humans ( Cummings et al. 2010 , Silverman et al. 2012 ). Animal studies have also shown positive effects of these SERMs at both vertebral and non

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Thomas Funck-Brentano Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Karin H Nilsson Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Robert Brommage Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Petra Henning Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Ulf H Lerner Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Antti Koskela Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland

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Juha Tuukkanen Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland

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Martine Cohen-Solal BIOSCAR UMRS 1132, Université Paris Diderot, Sorbonne Paris Cité, INSERM, Paris, France

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Sofia Movérare-Skrtic Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Claes Ohlsson Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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was followed by further evidence of the role of WNTs in the tumorigenesis of various human cancers in β-catenin-dependent or -independent pathways ( Anastas & Moon 2012 ). The importance of the WNT signaling pathway in bone homeostasis was highlighted

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K L Gustafsson Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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K H Nilsson Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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H H Farman Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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A Andersson Center for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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V Lionikaite Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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P Henning Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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J Wu Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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S H Windahl Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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U Islander Center for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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S Movérare-Skrtic Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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K Sjögren Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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H Carlsten Center for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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J-Å Gustafsson Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA

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C Ohlsson Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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M K Lagerquist Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Introduction Estrogen, the main female reproductive hormone, is a major regulator of bone homeostasis and it is well known that estrogen deficiency after menopause increases fracture risk and that estrogen treatment decreases this risk

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Lina Lawenius Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Hannah Colldén Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Karin Horkeby Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Jianyao Wu Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Louise Grahnemo Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Liesbeth Vandenput Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia

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Claes Ohlsson Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Klara Sjögren Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Introduction Osteoporosis is a debilitating disease affecting one in two women and one in five men after 50 years of age ( Sambrook & Cooper 2006 ). Both men and women lose bone in an age-dependent manner because of decreasing sex hormone

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Vikte Lionikaite Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Karin L Gustafsson Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Anna Westerlund Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Sara H Windahl Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Antti Koskela Department of Anatomy and Cell Biology, Medical Research Center, University of Oulu, Oulu, Finland

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Juha Tuukkanen Department of Anatomy and Cell Biology, Medical Research Center, University of Oulu, Oulu, Finland

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Helena Johansson Institute for Health and Aging, Catholic University of Australia, Melbourne, Australia

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Claes Ohlsson Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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H Herschel Conaway Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

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Petra Henning Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Ulf H Lerner Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Wiseman et al. 2017 ). In humans, increased vitamin A consumption and elevated serum retinol levels have been associated with increased bone fragility and fracture risk ( Melhus et al. 1998 , Whiting & Lemke 1999 , Feskanich et al. 2002

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