Zoledronic acid in the management of bone disease as a consequence of multiple myeloma: a review

Abstract

Background: Multiple myeloma (MM) is a haematological cancer associated with organ damage, essentially bone damage. MM continues to be considered an incurable disease and requires significant therapeutic resources. Aim: This manuscript presents a literature review of the utility of zoledronic acid (zoledronate) in the management of bone disease in MM. Discussion: The clinical benefit of bisphosphonates in the prevention and treatment of bone disease in MM has been demonstrated in the last 10 years. A recent network meta-analysis has evaluated 20 randomised clinical trials with nearly 7000 patients with myeloma enrolled and confirms the role of these agents in the prevention of pain, bone fractures and other skeletal-related events (SRE) in MM. However, their role on survival remains unclear. Zoledronate has shown significant reductions in SRE compared with placebo or other agents with acceptable tolerability, and recent studies have shown antitumoural effects for this agent, with a marginal survival benefit demonstrated in MM. Conclusions: Zoledronate prevents SRE in MM and presents a marginal survival benefit that deserves further investigation in controlled studies. Current clinical guidelines should be followed regarding the appropriate use of zoledronate in MM, to enhance its effects and to minimise its potential toxicity.

Multiple myeloma in the marrow: pathogenesis and treatments

“…MM progression and drug resistance depend on interactions with the local microenvironment; therapies that target the marrow microenvironment rather than the tumor cells directly, such as bisphosphonates, have proven to be effective in inhibiting tumor growth and osteolysis, suggesting that targeting of the marrow can be an effective therapeutic avenue to pursue. [5][6][7][8][9][10] In addition to osteoblasts (OBs) and OCs, other BM niche cells, including mesenchymal stem cells (MSCs), BM adipocytes, immune cells, and osteocytes, also likely affect MM progression. 7 BM cells exist in a dynamic, stress-sensing environment where they release soluble signaling molecules to communicate with one another; how these signals are processed by MM cells invading the BM niche remains a key area of investigation.…”

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction

“…Zoledronic acid (ZOL) is a third‐generation bisphosphonate, which can inhibit bone destruction in patients with metastatic bone tumors or multiple myeloma . Moreover, ZOL has been shown to exert an antitumor effect against osteosarcoma cells .…”

“…Zoledronic acid (ZOL) is a third-generation bisphosphonate, which can inhibit bone destruction in patients with metastatic bone tumors (11)(12)(13) or multiple myeloma. (14) Moreover, ZOL has been shown to exert an antitumor effect against osteosarcoma cells. (15)(16)(17) When ZOL was combined with chemotherapeutic agents, combination therapy showed a synergistic antitumor effect against osteosarcoma and prostate cancer cells.…”

Management of Pathologic Fractures Around the Hip: Part 1–Femur

“…The use of bisphosphonates has been shown to increase the length of time between diagnosis of metastatic disease and first occurrence of a skeletal-related event in patients with multiple myeloma, metastatic breast cancer, metastatic lung cancer, metastatic prostate cancer, and metastatic kidney cancer. 16,[19][20][21][22] Two of these studies also showed clinically significant reduction in perceived bone pain by patients with multiple myeloma and metastatic breast cancer with such treatment. 19,20 For patients presenting with impending or completed pathologic fracture not already taking bisphosphonates, consultation with their medical oncologist regarding initiation of bisphosphonate therapy may be necessary.…”