Re: Henry Henk, April Teitlelbaum, Satyin Kaura. Evaluation of the clinical benefit of long-term (beyond 2 years) treatment of skeletal-related events in advanced cancers with zoledronic acid. Curr Med Res Opin 2012;28(7):1119–27.
I read with great interest the paper by Henk et al. entitled "Evaluation of the clinical benefit of long-term (beyond 2 years) treatment of skeletal-related events in advanced cancers with zoledronic acid"1. This work addressed the fact that zoledronic acid prevents bone loss in patients with multiple myeloma. I would like to complete the discussion of Henk and colleagues by introducing a major complementary route by which zoledronic could reduce bone loss.
Recent studies have shown that bone loss in multiple myeloma is associated with increased osteoclast activity2. The osteoclasts are recruited from pre-osteoclasts by expression of the ligand for receptor activator of nuclear factor kappa b (RANKL). The critical role of RANKL in bone loss is evidenced by the inhibitory effect of osteoprotegerin (a decoy receptor of RANKL)3. Also, fusion of the cell membrane of the pre-osteoclasts is an essential step in the production and maturity of the osteoclasts. Cholesterol in the membranes of pre-osteoclasts plays an important role in the formation of the osteoclasts via cellular membrane fusion events4. Cholesterol in the cell membrane is produced from de novo synthesis through 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase5.
Zoledronic acid, which is used in the treatment of osteoporosis is assigned to a class of pharmaceuticals called bisphosphonate; it not only effectively inhibits the HMG CoA reductase pathway by binding and blocking the enzyme, farnesyl pyrophosphate synthase, but also stimulates osteoprotegerin production which can lead to a significant reduction of RANKL6. Therefore, these important mechanisms should be borne in mind when investigating the reduction of bone loss in patients with multiple myeloma.
Hamid Namazi
Shiraz University of Medical Sciences
Shiraz, Iran
Tel.: +98 711 6246093; [email protected]
Editor’s note
Authors thank the reader for this letter
but have no further comments.
References
- Henk H, Teitelbaum A, Kaura S. Evaluation of the clinical benefit of long-term (beyond 2 years) treatment of skeletal-related events in advanced cancers with zoledronic acid. Curr Med Res Opin 2012;28:1119-27
- Silvestris F, Ciavarella S, Strippoli S, et al. Cell fusion and hyperactive osteoclastogenesis in multiple myeloma. Adv Exp Med Biol 2011;714:113-28
- Trouvin AP, Goëb V. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss. Clin Interv Aging 2010;5:345-54
- Luegmayr E, Glantschnig H, Wesolowski GA, et al. Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins. Cell Death Differ 2004;11:108-18
- Singh N, Tamariz J, Chamorro G, et al. Inhibitors of HMG-CoA reductase: current and future prospects. Mini Rev Med Chem 2009;9:1272-83
- Dalle Carbonare L, Zanatta M, Gasparetto A, et al. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management. Drug Healthc Patient Saf 2010;2:121-37