Bisphosphonates have a widely recognized antiosteo-clastic activity and have been shown to decrease skeletal events in patients with MM.78 There is growing evidence of direct antitumor action of bisphosphonates on MM cells. Bisphosphonates act through inhibition of the ubiquitous mevalonate pathway, inducing apoptosis of tumor cells, suppressing proliferation and migration of endothelial cells, and by inhibiting angiogenesis.76 In addition, bisphosphonates decrease IL-6 production and induce apoptosis of osteoclasts through inhibition of farnesyl and gernanyl trans-ferase activity. Bisphosphonates increase 78 T cells, which cause increased apoptosis of the MM cells.79 Immunomodulatory effects of bisphosphonates are further being explored.

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