Investigational anabolic agents for the treatment of osteoporosis: an update on recent developments

ABSTRACT

Introduction: Teriparatide, a PTH analogue, was the first anabolic agent to be approved for the treatment of osteoporosis in 2002. Abaloparatide was also recently approved by the FDA. The need for other anabolic agents is still unmet.

Areas covered: In this review, we discuss target molecules and recent advances in the field of anabolic therapy for osteoporosis. PTH and PTHrP analogues binding to the PTH receptor and different routes of administration of teriparatide to avoid the burden of daily subcutaneous injections are discussed. We also review antibodies targeting suppressors of the Wnt pathway such as sclerostin and Dickopff-1.

Expert opinion: The development of alternative ways of administering PTH receptor ligands is a promising field, especially via the transdermal route. Other more promising molecules are still at very early stages of development. FDA recently requested more data on Romosozumab.

KEYWORDS:

• Abaloparatide
• arrestin
• calcilytic
• romosozumab
• sclerostin
• teriparatide

Article highlights

• Dissociation of bone formation from resorption would maximize the effect of an osteoanabolic treatment on bone accrual

• Parathyroid hormone (PTH) binding to its receptor (PTH1R) activates multiple signaling pathways, depending on the target cell and the pattern of PTH/PTH1R interaction. Activation of different pathways may lead to diverse or even opposite effects.

• The N-terminal PTHrP analogue abaloparatide was recently approved by the FDA. Alternative routes of PTH 1-34 delivery (oral, transdermal), the PTH analog ostabolin, and PTHrP 1-36 are also tested

• Sclerostin neutralization seems the most appealing target to intervene with Wnt signaling in a bone favoring way. Romosozumab is nearing to obtain approval for the treatment of osteoporosis

• Calcilytics have not been proved effective in the management of osteoporosis so far

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to thank Dimitri Koutsomitis for his kind support with illustrations

Declaration of interest

A. D. Anastasilakis has received lecture fees and research grants from Amgen; lecture fees from Lilly, ITF Hellas, ELPEN, VIANEX; and was principal investigator in the ARCH study. P. Makras has received lecture fees and research grants from Amgen and Gilead; lecture fees from Glaxo, Lilly, Pfizer, Leo, Genesis, ELPEN, VIANEX, Rafarm; and was also principal investigator in the ARCH study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.