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PTH and PTHrP Analogs: Treatment of Osteoporosis

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Osteoporosis

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Until 2002, antiresorptive agents defined our pharmacological approach to osteoporosis. With the introduction of teriparatide, PTH (1-34), and, more recently abaloparatide, PTHrP (1-34), as treatments for osteoporosis, we now have available a class of drugs that reduce fracture risk by completely different mechanisms. By stimulating bone formation to a greater extent and earlier than bone resorption, teriparatide and abaloparatide improve not only bone mineral density (BMD) but also the skeletal microarchitecture. Altogether, these properties have the potential to reconstruct the skeleton in a disease characterized by abnormal skeletal microstructure. The molecules showed somewhat different osteoanabolic profiles, although they act on the same receptor, namely, the PTH receptor type 1 (PTH1R). The RG conformation of the PTH1 receptor is associated with a much more transient interaction with its cognate ligands (e.g., PTH and PTHrP) than the R0 conformation in which the interaction is longer-lived. Theoretically, the affinity of a PTH or PTHrP ligand for the RG conformation, or a preferential ratio of affinity RG > R0, would help to define actions as more anabolic. Abaloparatide appears to have a markedly reduced affinity for R0 and thus a ratio of RG:R0 that is greater than teriparatide.

Since PTH and antiresorptives operate by completely different mechanisms, the rationale for combination therapy is attractive. Further work has provided new insights into how antiresorptive agents and PTH can be used in sequence or in combination for maximal therapeutic benefits.

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Authors and Affiliations

  1. Unit of Endocrinology and Diabetes, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

    Gaia Tabacco

  2. Division of Endocrinology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Gaia Tabacco & John P. Bilezikian

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  1. Massachusetts General Hospital, Boston, MA, USA

    Benjamin Z. Leder

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    Marc N. Wein

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Tabacco, G., Bilezikian, J.P. (2020). PTH and PTHrP Analogs: Treatment of Osteoporosis. In: Leder, B., Wein, M. (eds) Osteoporosis. Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-319-69287-6_17

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