The Mount Sinai Bone Program

History of The Mount Sinai Bone Program

Created in 1999, The Mount Sinai Bone Program has achieved international prominence by making seminal discoveries on how the vertebrate skeleton is modeled and remodeled in health and disease.  The basic and translational studies have used cutting-edge approaches to examine many facets of bone physiology, including regulation of the skeleton by hormones, enzymes, autocoids, second messengers, and transcriptional regulators.  By studying the pathophysiology of bone and mineral disorders, studies have helped unmask actionable therapeutic targets.  This Program has been funded by the National Institutes of Health and multiple other funding agencies since its inception.  With research laboratories based at Icahn School of Medicine at Mount Sinai, the Program has also provided clinical care for patients with osteoporosis, metabolic bone diseases, and rare bone disorders.

Early Research Contributions

Landmark discoveries by members of The Mount Sinai Bone Program include the first description of calcium sensing in the osteoclast, the cell that removed old bone, as a primary physiologic mechanism for the control of excessive bone removal.  The group also discovered that nitric oxide regulates bone remodeling, an observation that has led to the testing of nitric oxide donors for use in human osteoporosis.  In 2003, they established, for the first time, the existence of a pituitary-bone axis, which has revolutionized the way we view endocrine physiology.  In this new arm of skeletal regulation, the pituitary hormones TSH, ACTH, FSH, oxytocin and vasopressin, previously thought solely to stimulate single targets, bypass these organs to affect the skeleton directly.  These studies implicate pituitary hormones in the pathophysiology of osteoporosis, shifting the paradigm from our traditional, one–disease–one–hormone hypothesis to a multifaceted pathophysiology with enormous future therapeutic implications.  The group has also delineated the effects of genetic diseases, including Gaucher Disease and Congenital Adrenal Hyperplasia, on the skeleton, and probed the pathophysiology of osteoporosis resulting from aging, the menopause, thyroid disease, pregnancy and lactation, hyponatremia, smoking, and organ transplantation.  In addition, the group has also focused on the role of the nervous system and muscle in skeletal regulation, mechanisms that regulate cartilage homoeostasis, the crossover of anti-cancer and anti-osteoporosis drugs, and the use of stem cells to promote skeletal regeneration.

Recent Research Highlights

  • Zaidi Group
    Aside from providing the first evidence for a pituitary–bone axis (Cell, 2003, 2006), in two recent papers published in Nature, the Zaidi group found that genetic or pharmacological inhibition of FSH not only increases bone mass, but also reduces body fat and prevents neurodegeneration. In essence, this laid a firm foundation for a single anti-FSH agent to treat osteoporosis, obesity, and Alzheimer’s disease that affect millions of men and women worldwide.  This corpus of work was selected by Nature Medicine as one of eight “Notable Advances” in biomedicine for 2017 and was editorialized in the New York Times. The Zaidi group have now developed a novel humanized FSH-blocking antibody, which is undergoing preclinical testing.
  • Yuen and Kim Group
    The Yuen and Kim groups collaboratively showed that inhibitors of the enzyme phosphodiesterase 5A (PED5A)—drugs used for erectile dysfunction—are potent stimulators of bone formation and can potentially be repurposed for osteoporosis.
  • Ginzburg Group
    The Ginzburg group discovered that erythroferrone (ERFE), a molecule that regulates hepcidin and iron metabolism, regulates bone formation by binding to bone morphogenetic proteins. These studies focus on the role of ERFE in the pathophysiology of bone loss in β-thalassemia.

CURRENT GRANTS

  • 2019–2024
    FSH – an Aging Hormone?
    National Institute on Aging
    U19 AG060917
    PI: Mone Zaidi, Clifford James Rosen

  • 2021-2023
    A Humanized Monoclonal FSH Blocking Antibody for Alzheimer’s Disease
    National Institute of Aging
    U01 AG073148
    PI: Mone Zaidi, Tony Yuen

  • 2021–2026
    Proof-of-Concept and Mechanistic Studies to Repurpose Erectile Dysfunction Drugs for Elderly Females
    National Institute on Aging
    R01 AG071870
    PI: Tony Yuen, Se-Min Kim, Mone Zaidi

  • 2015–2026
    The Role of Erythroferrone in Regulating Bone Metabolism in Beta-Thalassemia
    National Institute of Diabetes, Digestive and Kidney Diseases
    R01 DK107670
    PI: Yelena Ginzburg, Tony Yuen, Mone Zaidi

  • 2021-2023
    Elevated FSH – A Driver for Sex Differences in Alzheimer’s Disease
    National Institute of Aging
    R01 AG074092
    PI: Mone Zaidi, Vahram Haroutunian, Tony Yuen

  • 2022-2023
    Mechanistic Understanding of Dysregulated Iron Metabolism in Polycythemia Vera
    National Institute on Diabetes, Digestive and Kidney Diseases
    R56 DK132146
    PI: Yelena Ginzburg, Ronald Hoffman

  • 2012-2023
    Regulatory Role of Transferrin in Erythropoiesis and Iron Metabolism
    National Institute of Diabetes, Digestive and Kidney Diseases
    R01 DK095112
    PI: Robert Fleming (Saint Louis University), Yelena Ginzburg, Stefano Rivella (Saint Louis University)

Prior NIH Grants

  • 2017–2022
    Thyrotropin Receptor, Thyrotropin and Mechanisms of Bone Loss
    National Institute of Diabetes, Digestive, and Kidney Diseases
    R01 DK113627
    PI: Mone Zaidi, Terry Francis Davies, Jameel Z Iqbal
  • 2014–2019
    Ahr and Osteoporosis
    National Institute of Arthritis and Musculoskeletal and Skin Diseases
    R01 AR067066
    PI: Mone Zaidi, Narayan G Avadhani
  • 2013–2018
    Understanding the skeletal phenotype of Gaucher disease
    National Institute of Arthritis and Musculoskeletal and Skin Diseases
    R01 AR065932
    PI: Mone Zaidi, Pramod K Mistry
  • 2011–2016
    Exploring the Posterior Pituitary-Bone Connection
    National Institute on Aging
    R01 AG040132
    PI: Mone Zaidi
  • 2009–2014
    TSH and Bone
    National Institute of Diabetes, Digestive and Kidney Diseases
    R01 DK080459
    PI: Mone Zaidi, Terry Francis Davies, Li Sun
  • 2003–2013
    Role of FSH in Osteoclast Formation and Function
    National Institute on Aging
    R01 AG023176
    PI: Mone Zaidi

  • 2003–2008
    Calcium in the Regulation of Osteoclast Formation
    National Institute of Aging
    R01 AG023176
    PI: Mone Zaidi

Mone Zaidi

Awards and Memberships

  • 2023: AAIM Special Recognition Award, Alliance of Academic Internal Medicine
  • 2020: Elected Deputy Editor for Medicine, eLife
  • 2022: International Research Prize, Austrian Bone and Mineral Society
  • 2019: Elected as Fellow of the American Association for the Advancement of Science
  • 2019: Fellowship of American Society for Bone and Mineral Research (Class of 2019)
  • 2019: The J. Lester Gabrilove Award, Mount Sinai Alumnus Association
  • 2018: David Sirota Endocrinologist–of–the–Year, Mount Sinai
  • 2018: Elected as Honorary Member Tinsley Harrison Society, Vanderbilt University School of Medicine
  • 2018: Elected as Foreign Fellow of the National Academy of Sciences of India
  • 2017: Harrington Scholar–Innovator Award, Harrington Discovery Institute
  • 2016: Faculty Council Award for Academic Excellence, Mount Sinai
  • 2016: The Practitioners Society (by invitation, oldest medical society in the US)
  • 2016–2018: President, Interurban Clinical Club (Founder: Sir William Osler, 1905)
  • 2014: Association of Professors of Medicine, by nomination
  • 2013–2016: Elected Secretary-Treasurer of the Interurban Clinical Club
  • 2010: Member, College of CSR Reviewers, NIH
  • 2005: Elected as Member, Association of Osteobiology
  • 2004: Elected as Member, Interurban Clinical Club [Councilor for New York, 2010-2013]
  • 2004: Elected as Association of American Physicians
  • 2002-2003: Chair, NIH Orthopedics and Musculoskeletal Study Section
  • 2003-2006: Chair, VA Merit Review Study Section

Recognition and Keynote Talks

  • 2023: Fellowship of the National Academy of Inventors, Class of 2023
  • 2022: Doctor of Science, Honoris Causa, King George’s Medical College, India
  • 2022: Honorary Fellowship, British Pharmacological Society
  • 2022: Plenary Lecture, Korean Society of Osteoporosis
  • 2022: Keynote Prize Lecture, Austrian Bone and Mineral Society, St Wolfgang
  • 2021: “Lightning Talk”, Open Access Publishing, Charité––Universitätsmedizin Berlin
  • 2019: Keynote Speaker, Qatar University Health Research Day
  • 2018: Harrison Society Visiting Professor, Vanderbilt University School of Medicine
  • 2017: Paper in Nature selected as one of eight “Notable Advances 2017” by Nature Medicine
  • 2017: Doctorate of Science Honoris Causa, Amity University, India
  • 2014: Honorary Member, International Chinese Musculoskeletal Research Society
  • 2013: Doctor of Science Honoris Causa, Sanjay Gandhi Postgraduate Institute of Medical Sciences, India
  • 2011–2016: Honorary Professor, Wuhan University Medical School (2011–2016)
  • 2010: Laurea Honoris Causa (Honorary Doctorate in Medicine), University of Bari, Italy
  • 2010: Lection Magistralis, University of Bari
  • 2008: Professor S.H. Zaidi Memorial Oration, Indian Toxicology Research Institute, India
  • 2007: Kramer Visiting Professor, Dartmouth Medical School
  • 2006: Highlight Speaker, National Institute on Aging (NIA) Council
  • 2006: Guest Speaker, Japanese Society for Bone and Mineral Research

Tony Yuen

  • 2023: Senior Editor, eLife
  • 2022: Elected Member, Association of Osteobiology
  • 2021: Associate Editor, Frontiers in Pediatrics
  • 2021: Associate Editor, Frontiers in Endocrinology
  • 2020: Section Editor, Encyclopedia of Bone Biology
  • 2013: Associate Editor, Genetic Steroid Disorders

 Yelena Ginzberg

  • 2023: Member, Editorial Board, American Journal of Hematology
  • 2022: Associate Editor, Frontiers in Hematology, Red Cells, Iron and Erythropoiesis Section
  • 2022: Member, Editorial Board, Blood
  • 2021: Member, Board of Reviewing Editors, eLife
  • 2021: Councilor, Interurban Clinical Club (ICC)
  • 2009: Elected Member, International BioIron Society (IBIS)
  • 2009-2011: Member, New York Academy of Sciences (NYAS)

Se-Min Kim

  • 2023: Reviewing Editor, eLife
  • 2023: Committee of InternationalLiaison, Korean Endocrine Society
  • 2022: Reviewing Editor, Frontiers in Endocrinology
  • 2022: Member, Endocrine Society 
  • 2018: Member, American Society of Bone and Mineral Research