Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

Abstract

Objective: Multiple Myeloma (MM) is characterized by uncoupling of bone resorption from bone formation which leads to the predominance of resorption. Bisphosphonates are chemical compounds that selectively concentrate at the interface of the active osteoclasts and the bone resorption surface where they inhibit osteoclast activity. Aim of this study was to describe cytokines behaviour in MM and to evaluate whether zoledronic acid could have an in vivo anti-angiogenic property in MM as observed in solid tumours.Methods: Serum samples from 29 (16 males and 13 females) consecutive MM patients with lytic bone lesions treated with 4 mg of zoledronic acid were tested for platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor (TNF α) and insulin growth factor (IGF-I). Basal cytokine levels were compared with the values observed after 1, 2, 7 and 21 days of treatment, using the Wilcoxon's test for nonparametric-dependent continuous variables.Results: A significant increase in IL-6 and TNF α was observed on days 1 and 2. As for VEGF, the levels of this cytokine did not change significantly from basal values during the entire period of observation except for a significant increase day 7 (P=0.0005). Moreover, PDGF significantly decreased (P=0.005) after 2 days from zoledronic acid infusion. Conclusions:From this study appears that in MM, treatment with zoledronic acid induces a transient reduction in PDGF according with previous studies in solid cancer, while the increase of IL-6 and VEGF could be related through a paracrine mechanism. The anti-myeloma effect of this drug could be driven through this mechanism.

Multiple myeloma and the challenges of its management in Nigeria

“…A pilot study described the roles of these cytokines in bone tissue destruction and the effect of Zoledronic acid (a bisphosphonate) in their chemical behaviors in MM patient. 7 Other complications such as anemia, nephropathy and constipation accounted for 61.5%, 23% and 19% in newly diagnosed MM patients in Nigeria. 4 Table 1 Criteria for the diagnosis of MM The staging of MM is another important step after diagnosis in the management of the disease.…”

Management of Multiple Myeloma in Developing Countries

“…IL-6, an important osteoclast-activating cytokine, plays an important role in the pathogenesis of osteoporosis in MM [21]. Annibali et al [22], in their pilot study, described the roles of these cytokines in bone tissue destruction and the effect of zoledronic acid (a bisphosphonate) on their chemical behaviors in MM patients. Other complications such as anemia, hemiplegia, nephropathy, and constipation accounted for 61.5%, 35%, 23%, and 19% of newly diagnosed MM patients in same study.…”

“…BPs are useful in preventing, reducing, and delaying MM SREs such as bone pain, osteoporosis, and other lytic bone lesions. They can also help to control the growth of extramedullary tumors, hence the need to scale-up their usage in MM [22,28].…”