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Joseph Zerwekh (Dallas, USA)

New and emerging therapies in the treatment of osteoporosis

Topics to be covered

In the last decade there have been tremendous advances in understanding the molecular basis of bone remodeling. While by no means complete, this new appreciation of bone cell biology has helped to explain some of the defects contributing to various diseases of the skeleton. More importantly, it has also opened a new avenue into potential therapies based on key proteins and transcription factors that regulate bone cell proliferation and activity. Most of these molecular approaches have been evaluated only in animal studies as proof of concept but a few have evolved to phase two and three studies.
I would like to begin my session with a brief consideration of two key molecular components involved in bone cell differentiation and proliferation, namely the RANKL/OPG system for osteoclastogenesis and the Wnt/ß-catenin signaling mechanism in osteoblasts. In so doing, key molecular signaling molecules and their functions would be highlighted as potential targets for molecular inactivation. I propose to do this as non-pharmacologic approaches that have used vibration and as pharmacologic approaches with molecules that affect either osteoclastogenesis or osteoblastogenesis. These molecules include RANKL/OPG, cathepsin K inhibitors, and new SERMS as antiresorptive approaches and calcium sensing receptor antagonists, R-spondin1, and monoclonal antibodies to sclerostin and Dkk1 as anabolic approaches.

Educational goals

After attending this Meet the Professor session, participants will be expected to:

• describe the coupled process of normal bone remodeling and its alterations in postmenopausal osteoporosis;
• describe the major targets of molecular therapy, namely the RANKL/OPG and Wnt/ß-catenin signalling systems;
• review the recent studies with Denosumab, Odanacatib, and new SERMS
• review recent studies with new anabolic agents.

These are tentative general educational goals that could change as additional information comes to press between now and the meeting.

Target audience

This session should be of interest to both basic scientists and clinical investigators interested in new therapeutic options for osteoporosis and their current state of development with respect to efficacy and potential limitations.

Teaching methods

This is a difficult topic in which to involve the audience. I anticipate that I might poll the audience as to whether they are basic researchers or clinicians and then present one or two clinical cases that represent ideal candidates for one or more of the to be described new potential therapeutic approaches. I would try and seek audience participation in the discussion of these cases.