E-Book, Englisch, 252 Seiten, eBook
Reihe: Current Clinical Oncology
ISBN: 978-1-60761-554-5
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark
Zielgruppe
Professional/practitioner
Autoren/Hrsg.
Weitere Infos & Material
Clinical Presentation of Myeloma Bone Disease.- Imaging of Multiple Myeloma, Solitary Plasmacytoma, MGUS, and Other Plasma Cell Dyscrasias.- Biochemical Markers of Bone Remodeling in Multiple Myeloma.- Radiation Therapy in Multiple Myeloma.- Surgical Management of Bone Disease.- Bisphosphonates in the Treatment of Myeloma Bone Disease.- Osteonecrosis of the Jaw.- Murine Models of Myeloma Bone Disease: The Importance of Choice.- RANK Ligand Is a Therapeutic Target in Multiple Myeloma.- Osteoclast Activation in Multiple Myeloma.- Potential Role of IMiDs and Other Agents as Therapy for Myeloma Bone Disease.- Proteasome Inhibitors and the Wnt Signaling Pathway in Myeloma Bone Disease.- Mechanisms Involved in Osteoblast Suppression in Multiple Myeloma.
"Chapter 10 Osteoclast Activation in Multiple Myeloma (p. 183-184)
Sonia Vallet and Noopur Raje
Abstract Osteolytic bone disease affects more than 80% of multiple myeloma (MM) patients with a negative impact on both quality of life and overall survival. The pathogenesis of osteolytic disease resides in increased osteoclast (OC) activation along with osteoblast (OB) inhibition resulting in altered bone remodeling. OC number and activity in MM are enhanced mainly via cytokine deregulation within the bone marrow (BM) milieu and an imbalance of the OC/OB axis. Several novel agents are currently under investigation for their positive effect on bone remodeling via OC inhibition or OB activation. In addition to restoring bone remodeling, these drugs may inhibit tumor growth in vivo. Therefore, targeting bone disease is a promising therapeutic strategy not only with the goal of alleviating morbidity from bone disease but also resultant anti-tumor activity.
Keywords Osteolysis · MM niche · Osteoclast activation · Osteoblasts
10.1 Introduction
Osteolytic lesions are a pathognomonic feature of multiple myeloma (MM). More than 80% of MM patients develop osteolytic bone disease (OBD), frequently complicated by skeletal-related events (SRE) such as severe bone pain, vertebral compression fractures, and pathologic fractures resulting in a need for radiation or surgical fixation. Importantly, pathologic fractures affect 40–50% of MM patients increasing the risk of death by more than 20% compared to the patients without fractures [1, 2].
Therefore, OBD reduces not only patients’ quality of life but also survival. The pathogenesis of OBD in MM is primarily associated with generalized osteoclast (OC) activation. Bone marrow (BM) biopsies from MM patients show a correlation between tumor burden, OC number, and resorption surface [3, 4]. Although enhanced OC function is a key player in the development of OBD, a decrease in trabecular thickness and low calcification rate in BM biopsy specimens ofMMpatients with osteolysis suggest that osteoblast (OB) activity is also impaired [5].
Therefore, the bone remodeling balance in MM is disrupted by a deregulation of the OC/OB axis. Several novel agents are aimed at restoring bone homeostasis targeting either OC or OB activity. Interestingly, inhibition of osteolysis leads to reduced tumor growth in vivo [6, 7]. Therefore, novel agents targeting bone disease are promising therapeutic strategies for the treatment of MM. Optimal drug development requires further clarification of the pathogenesis of osteolysis as well as understanding the role of the microenvironment in the progression of myeloma."
