1. ¹Department of Hematology and Medical Research, 251 General Air Force Hospital, Athens, Greece
2. ²Department of Hematology, Imperial College London, Hammersmith Hospital, London, UK
3. ³Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece
4. ⁴Department of Hematology and Oncology, Charité-Universitaetsmedizin Berlin, Berlin, Germany

Correspondence: Dr E Terpos, Department of Hematology and Medical Research, 251 General Airforce Hospital, 3 Kanellopoulou Street, GR-11525 Athens, Greece. E-mails: e.terpos@imperial.ac.uk; eterpos@hotmail.com

Received 23 March 2007; Revised 14 May 2007; Accepted 31 May 2007; Published online 5 July 2007.

Abstract

Immunomodulatory drugs (IMiDs) and bortezomib have been recently used in the management of patients with both newly diagnosed and relapsed/refractory multiple myeloma. Except of their direct anti-myeloma effect, these agents also alter the interactions between myeloma cells and marrow microenvironment. Several recent studies have investigated their potential effect on myeloma bone disease. Preclinical studies have demonstrated that IMiDs reduce osteoclast formation and function in vitro. Clinical studies have confirmed that thalidomide reduces markers of bone resorption, while lenalidomide induces osteoclast arrest in myeloma patients. However, IMiDs seem to have no effect on osteoblast exhaustion present in myeloma. The proteasome inhibitor bortezomib restores abnormal bone remodeling through the inhibition of osteoclast function and the increase in osteoblast differentiation and activity in vitro. In myeloma patients, bortezomib reduces biochemical markers of bone resorption and normalizes the RANKL/osteoprotegerin ratio, while at the same time increases bone formation markers reducing levels of dickkopf-1 protein. Whether these effects are direct and not only a consequence of the agents' antimyeloma activity is not totally clear. This review summarizes all available data for these attractive agents that combine potent anti-myeloma activity with beneficial effects on bone and may alter the way of management of myeloma-related bone disease.