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Parathyroid Hormone-Related Protein Analogs as Osteoporosis Therapies

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Abstract

The only bone anabolic agent currently available for osteoporosis treatment is parathyroid hormone (PTH)—either its N-terminal 1–34 fragment or the whole molecule of 1–84 aminoacids—whose intermittent administration stimulates new bone formation by targeting osteoblastogenesis and osteoblast survival. PTH-related protein (PTHrP) is an abundant factor in bone which shows N-terminal homology with PTH and thus exhibits high affinity for the same PTH type 1 receptor in osteoblasts. Therefore, it is not surprising that intermittently administered N-terminal PTHrP peptides induce bone anabolism in animals and humans. Furthermore, the C-terminal region of PTHrP also elicits osteogenic features in vitro in osteoblastic cells and in various animal models of osteoporosis. In this review, we discuss the current concepts about the cellular and molecular mechanisms whereby PTHrP may induce anabolic actions in bone. Pre-clinical studies and clinical data using N-terminal PTHrP analogs are also summarized, pointing to PTHrP as a promising alternative to current bone anabolic therapies.

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Acknowledgments

The authors of this review received grants from the Spanish Instituto de Salud Carlos III (RETICEF RD12/0043/0008 and RD12/0043/0022, PI11/00449) financed with FEDER funds. SP-N is the recipient of a post-doctoral research contract from RETICEF.

Contributors’ statement

PE designed the general layout of the review, performed most of the literature search, and prepared the first draft of the paper. SP-N designed figures 1 and 2. SH, XN, and AD-P were mostly responsible for reviewing and discussing the clinical studies, and designed figure 3 and Table 1. All authors revised the paper critically for intellectual content and approved the final version.

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Authors and Affiliations

  1. Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040, Madrid, Spain

    Pedro Esbrit & Sergio Portal-Núñez

  2. Universidad Autónoma de Madrid, Madrid, Spain

    Pedro Esbrit & Sergio Portal-Núñez

  3. Hospital del Mar-IMIM, Universidad Autónoma de Barcelona, Barcelona, Spain

    Sabina Herrera, Xavier Nogués & Adolfo Díez-Pérez

  4. Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF), Instituto de Salud Carlos III, Madrid, Spain

    Pedro Esbrit, Sabina Herrera, Sergio Portal-Núñez, Xavier Nogués & Adolfo Díez-Pérez

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  1. Pedro Esbrit
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  2. Sabina Herrera
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  5. Adolfo Díez-Pérez
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Correspondence to Pedro Esbrit.

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Conflict of interest

Adolfo Díez-Pérez is advisor or speaker for Lilly, Amgen, Pfizer, GSK, and Active Life Scientific. Pedro Esbrit, Sabina Herrera, Sergio Portal-Núñez, and Xavier Nogués declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving animals by the authors of this article were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Esbrit, P., Herrera, S., Portal-Núñez, S. et al. Parathyroid Hormone-Related Protein Analogs as Osteoporosis Therapies. Calcif Tissue Int 98, 359–369 (2016). https://doi.org/10.1007/s00223-015-0050-1

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  • DOI: https://doi.org/10.1007/s00223-015-0050-1

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