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Parathyroid hormone analogues in the treatment of osteoporosis

Nature Reviews Endocrinology volume 7, pages 647–656 (2011)Cite this article

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Abstract

Osteoporosis is characterized by the occurrence of fragility fractures. Over the past years, various treatment options have become available, mostly antiresorptive agents such as bisphosphonates. However, antiresorptive therapy cannot restore bone mass and structure that has been lost due to increased remodeling. In this case, recombinant human parathyroid hormone (PTH) analogues—the full-length PTH1–84 or the shortened molecule PTH1–34, which is also known as teriparatide—present the possibility of increasing the formation of new bone substance by virtue of their anabolic effects. The bone formation induced by PTH analogues not only increases BMD or bone mass but also improves the microarchitecture of the skeleton, thereby leading to improved strength of bone and increased mechanical resistance. Controlled trials have shown that both analogues significantly reduce the incidence of vertebral fractures, and PTH1–34 also reduces the risk of nonvertebral fractures. The need for daily self-injection and the higher cost compared with other forms of treatment limit the widespread use of PTH analogues. Nevertheless, treatment with PTH analogues should be considered in postmenopausal women and men with severe osteoporosis, as well as in patients on established glucocorticoid treatment with a high fracture risk. Concurrent therapy with antiresorptive agents should be avoided, but sequential therapy with these agents might consolidate the beneficial effects on the skeleton.

Key Points

  • Osteoporosis is characterized by a decrease in bone mass and alterations in bone architecture that increase bone fragility and risk of fracture

  • Agents that reduce bone resorption are primarily used today in the treatment of osteoporosis; however, they cannot restore bone mass and structure that has been lost due to increased bone remodeling

  • Therapy with recombinant human PTH analogues, such as PTH1–34 (teriparatide) and PTH1–84 (full-length PTH), can increase the formation of new bone substance

  • PTH analogues not only increase BMD or bone mass but also improve the microarchitecture of the skeleton, thereby improving bone strength as well as mechanical resistance

  • PTH analogues significantly reduce the incidence of vertebral fracture, whereas PTH1–34 also reduces the risk of nonvertebral fractures

  • Treatment with PTH analogues should be considered in postmenopausal women and men with severe osteoporosis, as well as in patients on established glucocorticoid treatment with a high risk of fractures

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Figure 1: Model of the mechanism of action of PTH on osteoblasts.
Figure 2: Schematic representation of the action of intermittent PTH on cells of the osteoblast lineage and on bone formation.
Figure 3: The anabolic window.
Figure 4: Effect of PTH1–34 on vertebral fracture risk.
Figure 5: Effect of PTH1–84 on vertebral fracture risk.

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  1. Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Petersgraben 4, Basel, CH-4031, Switzerland

    Marius E. Kraenzlin & Christian Meier

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M. E. Kraenzlin researched the data for the article. Both authors provided a substantial contribution to discussions of the content, contributed equally to writing the article and reviewed and/or edited the manuscript before submission.

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Kraenzlin, M., Meier, C. Parathyroid hormone analogues in the treatment of osteoporosis. Nat Rev Endocrinol 7, 647–656 (2011). https://doi.org/10.1038/nrendo.2011.108

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