Treatment of myeloma bone disease: When, how often, and for how long?

Abstract

The landscape of MM has changed dramatically in recent years. Several new and more effective treatments have been introduced that not only makes patients live longer but also brings them into a deeper remission. This makes the potential total exposure of bone protective treatment much higher but perhaps also less needed. New and more precise imagining techniques have been introduced making detection of bone disease more sensitive, and the introduction of SLiM-CRAB criteria have changed the parameters used in old clinical trials investigating treatment of MM bone disease. New data have also emerged investigating the effect of the RANKL inhibitor denosumab compared to zoledronic acid (ZOL). Randomized trials have investigated longer treatment durations, which becomes more relevant as patients now live longer. In addition in this review, data regarding interval between individual treatment, impact of remission status, new data in relation to rebound after discontinuation and of denosumab, as well as the rational for drug holidays before dental procedures will also be discussed.

Keywords: Bisphosphonates; Denosumab; Multiple myeloma; Myeloma bone disease; Zoledronic acid.

Fig. 1

Multiple Myeloma can increase bone degradation through a number of pathways including increasing RANK/OPG ratio and IL6 which increases osteoclast recruitment and maturation as well as inhibiting osteoblast directly (dickkopff1, sclerostin) or through inhibition of pathways essential for osteoblast function and maturation (WNT pathway, RUNX2). Denosumab Inhibit RANKL hereby suppressing osteoclast formation. Bisphosphonates are embedded into the bone and released to osteoclasts during bone absorption.