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Translational Endocrinology of Bone - 1st Edition - ISBN: 9780124157842, 9780124158597

Translational Endocrinology of Bone

1st Edition

Reproduction, Metabolism, and the Central Nervous System

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Editor: Gerard Karsenty
Hardcover ISBN: 9780124157842
eBook ISBN: 9780124158597
Imprint: Academic Press
Published Date: 11th October 2012
Page Count: 236
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The use of model organisms together with the power of genetics has profoundly affected our understanding of the physiology of one organ, the skeleton, in two distinct but complementary ways. This is the first translational reference to focus on these major conceptual advances in bone biology and their development in the clinic. Several advances have already been translated into therapies and others are being tested for diseases as different as osteoporosis, type-2 diabetes, and hypo-fertility. This book is a timely reference for both basic and clinical researchers in bone biology and endocrinology.

Key Features

  • Summarizes the latest research and translational applications of how the varied growth and development of bone affects appetite, metabolism, reproduction, and a wide range of endocrine functions
  • Provides a common language for bone biologists, endocrinologists, osteologists, and other researchers, such as neuroscientists, who study appetite, fuel metabolism and diabetes, to discuss the development of translational research and new therapeutic strategies for bone, metabolic, and neuro-endocrine diseases.
  • Saves researchers and clinicians time in quickly accessing the very latest details on a broad range of bone research and therapeutics, as opposed to searching through thousands of journal articles


Clinical and basic researchers in bone biology and clinician researchers in endocrinology, osteology, rheumatology, and orthopedic surgery.

Table of Contents



Chapter 1. Introduction: The Rational of the Work or the Overarching Hypothesis

The Two Faces of Physiology

The Unanticipated Influence of Bone on Whole-Organism Physiology


Chapter 2. Basic Principles of Bone Cell Biology


The Osteoblast Lineage


Bone Remodeling

Coupling of Bone Formation to Resorption in the BMU

Bone as an Endocrine Organ



Chapter 3. The Central Control of Bone Mass



Sympathetic Nervous System (SNS)


Neuromedin U

Neuropeptide Y (NPY) and NPY Receptors

Cocaine- and Amphetamine-Regulated Transcripts

Melanocortin and MC4R

The Cannabinoid System

Other Central Hormones and Neuropeptides Regulating Bone Remodeling


Chapter 4. Neuropeptide Y and Bone Formation

The Neuropeptide Y System

Neuropeptide Y and Bone Homeostasis

Other NPY Ligands

The NPY Receptors

NPY Interaction with Leptin in the Control of Bone Homeostasis

NPY’S Coordination of Body Weight and Bone Mass

Interactions Between NPY and Sex Hormones in the Control of Bone Homeostasis



Chapter 5. Serotonin: The Central Link between Bone Mass and Energy Metabolism

Energy Metabolism and its Regulation

Perturbations in Energy Metabolism and Bone Mass

Discovery of Leptin Regulation of Bone Mass

Gain of Function of Leptin Signaling and Bone Mass

Factors Downstream of Leptin Regulation of Bone Mass

Leptin Acts in the Brain to Regulate Bone Mass

Neurotransmitter Profiling in Leptin-Deficient Mice Brain Points to Serotonin as a Target of Leptin

Serotonin Uses Creb in Arc and Vmh Neurons to Regulate Two Different Functions

Leptin Receptor Deletion on Serotonin Nuclei Results in Increased Appetite




Chapter 6. Gastrointestinal Tract and the Control of Bone Mass

The Relevance of the Gastrointestinal Tract for the Skeleton

Hypochlorhydria, a Major Public Health Problem

Proton Pump Inhibitors and Osteoporosis

How are Proton Pump Inhibitors Affecting the Skeleton?

Gastrectomy and Osteomalacia, an Association not to be Forgotten

Osteopetrorickets, a Rare Disorder Caused by a Combined Acidification Defect of Osteoclasts and Parietal Cells

Animal Models of Impaired Gastric Acidification

Calcium Supplementation in Clinical Practice

Concluding Remarks


Chapter 7. Gut-derived Serotonin and Bone Formation

Serotonin: A Tale of Guts and Brain

Regulation of Bone Formation by Gut-Derived Serotonin

Regulation of Serotonin Production in Gut by Lrp5

Regulation of Bone Formation by Serotonin in Humans

Modulation of Tph1 Activity as a Novel Bone Anabolic Therapy


Chapter 8. Skeletal Actions of Insulin


The Insulin/IGF Family of Ligands and Receptors

Actions of IGF-1 and Insulin in Osteoblasts

Insulin Signaling in the Osteoblasts Regulates Glucose Metabolism

Insulin Signaling Regulates Osteocalcin Production and Bioavailability

From Mouse to Man

Perspectives and Directions for Future Studies



Chapter 9. Transcriptional Regulation of the Endocrine Function of Bone


Foxo1, A Transcriptional Modulator of the Endocrine Function of the Skeleton

Atf4 in Skeletal Regulation of Energy Homeostasis

ΔFosb Reciprocally Affects Bone Mass and Fat Accrual and Favors Insulin Sensitivity

Creb Versus Atf4 in Central Control of Bone Mass: Leptin

Creb in Central Versus Local Control of Bone Formation: Serotonin

Creb in Bone Regulation of Male Reproduction



Chapter 10. Regulation of Bone Resorption by PPARγ


PPARγ Expression Specifies Osteoclast Progenitor

PPARγ Activation Stimulates Osteoclast Differentiation by Inducing C-FOS

PPARγ Activation Stimulates Osteoclast Differentiation by Downregulating β-Catenin

PPARγ Activation Promotes Osteoclastogenesis by Activating PGC1β and ERRα

Other Signaling Pathways that may Intersect with PPARγ During Osteoclastogenesis

TZDS Induce Bone Loss by Activating Bone Resorption and Inhibiting Bone Formation

Systemic PPARγ Activation Enhances Bone Resorption by Both Osteoclast-Autonomous and Non-Autonomous Mechanisms

PPARγ Effects on Bone Resorption are Context Dependent




Chapter 11. From Gonads to Bone, and Back


Sex Steroid Hormones Effects on Bone Physiology

Sex Steroid Hormone Regulation of Bone Growth

Sex Steroid Hormone Regulation of Bone Mass Maintenance

Estrogen and Androgen Mode of Action in Skeleton

Genomic and Non-Genomic Sex Steroid Hormone Signaling in Bone Cells

Osteocalcin, a New Player in the Regulation of Testosterone Production

Osteocalcin Mode of Action in Leydig Cells

Correlative Observation of the Osteocalcin-Dependent Regulation of Testosterone Production in Humans

Disturbances in Osteocalcin or its Receptor Activity are Associated to Prostate Cancer



Chapter 12. Regulation of Phosphate Metabolism by FGF23


Phosphate Metabolism

FGF Biology

FGF23 and Phosphate Metabolism

FGF23: Emerging Roles in Disease Processes




Chapter 13. Clinical Aspects of Fibroblast Growth Factor 23


Hypophosphatemic Diseases

Treatment of FGF23-Related Hypophosphatemic Diseases

Tumoral Calcinosis

Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD)

FGF23 in Epidemiological Studies

Future Direction


Chapter 14. Bone Marrow Fat and Bone Mass


Historical Vignette

Molecular and Cellular Aspects of Marrow Adipogenesis

Development of Marrow Fat

The Function of Marrow Fat

Mouse Models to Study Marrow Adipocytes

Marrow Fat in Humans

Future Direction


Chapter 15. Osteocalcin, Undercarboxylated Osteocalcin, and Glycemic Control in Human Subjects

Obesity, Diabetes, and Low Serum Osteocalcin: Cross-Sectional Studies in Human Subjects

Osteocalcin and Glycemic Control: Interventional Studies

Interventional Studies Manipulating Vitamin K Levels

What is the Active Form of Osteocalcin in Humans?

Endosteal Surface Area, Remodeling, and Glycemic Control

Osteocalcin and Glycemic Control: Conclusions and Clinical Implications



Chapter 16. Clinical Implications of Serotonin Regulation of Bone Mass


Synthesis and Function of Serotonin in the Nervous System

Studies of Serotonin Influence on Bone in Human Development

Clinical Studies Demonstrating an Effect of Serotonin on Bone in Adults

Bone Density


Considerations for Determination of Causality in Epidemiologic Studies

Limitations of Current Studies on SSRIS’ Effect on Bone

Implications for Screening and Population Health



Chapter 17. Significance of Organ Crosstalk in Insulin Resistance and Type 2 Diabetes


Mechanisms of β-Cell Failure/Loss

Insulin Resistance—Multiorgan Crosstalk of Insulin Target Tissues

Non-Canonical Insulin Target Tissues

Therapy for Type 2 Diabetes Mellitus




Color Plates



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© Academic Press 2013
11th October 2012
Academic Press
Hardcover ISBN:
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About the Editor

Gerard Karsenty

Gerard Karsenty received his MD and PhD from the University of Paris, France and completed his post-doctoral training at the University of Texas MD Anderson Cancer Center in 1990. His laboratory has studied every aspect of skeletal biology ranging from cell differentiation to function. His laboratory was the first one to decipher the molecular bases of osteoblast-specific gene expression, work that culminated in the identification of Runx2 as the master gene of osteoblast differentiation. The overarching assumption of Dr. Karsenty’s work is that the appearance of bone during evolution has profoundly changed the physiology of animals because of the energetic cost that bone growth entails. Thus, over the last 10 years, his group has explored the hypothesis that the control of bone mass and energy metabolism must be coordinated and that this coordination is done, in large part, by hormones like leptin and osteocalcin that appear during evolution with bone. His lab has explored every aspect of this hypothesis through genetic and molecular means. Concurrent with this research, the Karsenty lab is exploring whether there are additional connections between bone physiology and the function of other organs such as fertility. This work culminated in the discovery that bone, via osteocalcin, regulates testosterone production.

Affiliations and Expertise

Professor and Chair, Department of Genetics and Development, Columbia University Medical School, New York, NY, USA


"This is a valuable contribution to the field of bone biology. It is a must read for all researchers in the field of bone pathology. It is also a good book for physicians caring for patients with bone disorders as it provides a review of bone pathology in the context of other body systems." Rating: 4, May 2, 2014
"…17 articles…discuss the effects of bone on whole-organism physiology and how the study of this discipline aids in the understanding of the pathogenesis of degenerative diseases affecting several organs. Chapters address various hormones and neuromediators ranging from serotonin to osteocalcin, as well as knowledge about the ability of bone to regulate phosphate metabolism.", March 2014

Ratings and Reviews