The role of leptin in regulating bone metabolism

  • Author Footnotes
    1 These authors contributed equally to this work.
    Jagriti Upadhyay
    Corresponding author at: VA Boston Healthcare System, Division of Endocrinology (9-B), 150S. Huntington Ave., Boston, MA 02130. Tel.: +1 857 364 4233.
    1 These authors contributed equally to this work.
    Division of Endocrinology, Boston VA Healthcare System/Harvard Medical School, Boston, MA 02215
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Olivia M. Farr
    1 These authors contributed equally to this work.
    Division of Endocrinology, Boston VA Healthcare System/Harvard Medical School, Boston, MA 02215
    Search for articles by this author
  • Christos S. Mantzoros
    Division of Endocrinology, Boston VA Healthcare System/Harvard Medical School, Boston, MA 02215
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  • Author Footnotes
    1 These authors contributed equally to this work.
Published:October 25, 2014DOI:


      Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature the indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk–benefit of leptin’s use in metabolic bone disease particularly in leptin deficient individuals.


      BMI (body mass index), ARC (arcuate nucleus of hypothalamus), NPY (neuropeptide Y), AgRP (agouti-related peptide), POMC (pro-opiomelanocortin), CART (cocaine- and amphetamine-related transcript), LepRb (leptin receptor), JAK2 (janus kinase 2), STAT3 (signal transducer and activator of transcription 3), SHP2 (src homology-2-containing protein tyrosine phosphatase 2), MAPK (mitogen-activated protein kinase), PI3K (phosphatidylinositol 3 kinase), AMPK (adenosine monophosphate-activated protein kinase), mTOR (mammalian target of rapamycin), FoxO1 (forkhead box protein O1), TSH (thyroid-stimulating hormone), FGF23 (fibroblast growth factor 23), VMH (ventromedial hypothalamus), IGF1 (insulin-like growth factor 1), IGF-BP2/3 (insulin-like growth factor binding protein 2/3), GH (growth hormone), ACTH (adrenocorticotropic hormone), HAART (highly active antiretroviral therapy), Akt (protein kinase B), SOCS-3 (suppressor of cytokine signaling 3)


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