G David Roodman1. 1. University of Pittsburgh, Veterans Affairs Pittsburgh Healthcare System, Department of Medicine/Hematology-Oncology, Pittsburgh, Pennsylvania 15240, USA. Roodmangd@upmc.edu.
Abstract
BACKGROUND: Multiple myeloma (MM) is a plasma cell malignancy in which osteolytic bone lesions develop in over 80% of patients. The increased bone destruction results from increased osteoclast formation and activity, which occurs adjacent to marrow sites involved with MM cells. This is accompanied by suppressed or absent osteoblast differentiation and activity, resulting in severely impaired bone formation and development of purely osteolytic lesions. OBJECTIVE: The pathophysiology underlying this bone remodeling is reviewed, and potential new strategies to treat MM bone disease are discussed. RESULTS: Recent advances in our understanding of factors involved in pathogenesis of MM bone disease have identified novel therapeutic targets. Several of these are or will be in clinical trials soon. CONCLUSION: Agents which target the tumor and bone-destructive process, such as the immunomodulatory drugs (IMiDs) or bortezomib, in combination with novel anti-resorptives should be effective. These combinations should be in clinical trials in the next few years. It is unclear if these treatments will be able to 'heal' bone lesions in MM patients.
BACKGROUND:Multiple myeloma (MM) is a plasma cell malignancy in which osteolytic bone lesions develop in over 80% of patients. The increased bone destruction results from increased osteoclast formation and activity, which occurs adjacent to marrow sites involved with MM cells. This is accompanied by suppressed or absent osteoblast differentiation and activity, resulting in severely impaired bone formation and development of purely osteolytic lesions. OBJECTIVE: The pathophysiology underlying this bone remodeling is reviewed, and potential new strategies to treat MM bone disease are discussed. RESULTS: Recent advances in our understanding of factors involved in pathogenesis of MM bone disease have identified novel therapeutic targets. Several of these are or will be in clinical trials soon. CONCLUSION: Agents which target the tumor and bone-destructive process, such as the immunomodulatory drugs (IMiDs) or bortezomib, in combination with novel anti-resorptives should be effective. These combinations should be in clinical trials in the next few years. It is unclear if these treatments will be able to 'heal' bone lesions in MMpatients.
Authors: Judith M Runnels; Alicia L Carlson; Costas Pitsillides; Brian Thompson; Juwell Wu; Joel A Spencer; John M J Kohler; AbdelKareem Azab; Anne-Sophie Moreau; Scott J Rodig; Andrew L Kung; Kenneth C Anderson; Irene M Ghobrial; Charles P Lin Journal: J Biomed Opt Date: 2011 Jan-Feb Impact factor: 3.170
Authors: Yi Qian; Debajyoti Bhowmik; Nandita Kachru; Rohini K Hernandez; Paul Cheng; Alexander Liede Journal: Support Care Cancer Date: 2017-10-23 Impact factor: 3.603
Authors: Evangelos Terpos; Gareth Morgan; Meletios A Dimopoulos; Matthew T Drake; Suzanne Lentzsch; Noopur Raje; Orhan Sezer; Ramón García-Sanz; Kazuyuki Shimizu; Ingemar Turesson; Tony Reiman; Artur Jurczyszyn; Giampaolo Merlini; Andrew Spencer; Xavier Leleu; Michele Cavo; Nikhil Munshi; S Vincent Rajkumar; Brian G M Durie; G David Roodman Journal: J Clin Oncol Date: 2013-05-20 Impact factor: 44.544
Authors: Dharminder Chauhan; Ajita V Singh; Mohan Brahmandam; Ruben Carrasco; Madhavi Bandi; Teru Hideshima; Giada Bianchi; Klaus Podar; Yu-Tzu Tai; Constantine Mitsiades; Noopur Raje; David L Jaye; Shaji K Kumar; Paul Richardson; Nikhil Munshi; Kenneth C Anderson Journal: Cancer Cell Date: 2009-10-06 Impact factor: 31.743