A Seckinger1, D Hose. 1. Medizinische Klinik V, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Deutschland, anja.seckinger@med.uni-heidelberg.de.
Abstract
BACKGROUND: Multiple myeloma is the malignant disease which most frequently leads to bone lesions. Approximately 80% of myeloma patients develop osteoporosis, lytic bone lesions (osteolysis) or fractures during the course of the disease. Of these patients 43% suffer pathological fractures most often of the vertebrae followed by fractures of the long bones. MATERIAL AND METHODS: The methods used in the described articles include, e.g. gene expression profiling, enzyme-linked immunosorbent assays and radiological techniques. RESULTS AND DISCUSSION: Myeloma bone disease represents a threefold therapeutic problem: (i) per se because of the associated morbidity, mortality and the accompanying decrease of quality of life, (ii) as survival space for (residual) myeloma cells after primarily successful chemotherapy and subsequently necessary chemotherapeutic treatment, and (iii) the occurrence of bone lesions in asymptomatic patients is the most common cause for the initiation of treatment to avoid myeloma-induced fractures. Myeloma cells harbor a high median number of chromosomal aberrations and multiple changes in gene expression compared to normal bone marrow plasma cells leading to the aberrant production of survival, proliferation, pro-angiogenic and bone turnover influencing factors or the induction of those factors in the bone marrow microenvironment. This causes an imbalanced bone turnover in the sense of an increased number and activity of osteoclasts while bone formation by osteoblasts is almost completely suspended. Therapeutic approaches, systemically and locally therefore aim at stimulation of osteoblasts and inhibition of bone resorption.
BACKGROUND:Multiple myeloma is the malignant disease which most frequently leads to bone lesions. Approximately 80% of myelomapatients develop osteoporosis, lytic bone lesions (osteolysis) or fractures during the course of the disease. Of these patients 43% suffer pathological fractures most often of the vertebrae followed by fractures of the long bones. MATERIAL AND METHODS: The methods used in the described articles include, e.g. gene expression profiling, enzyme-linked immunosorbent assays and radiological techniques. RESULTS AND DISCUSSION: Myeloma bone disease represents a threefold therapeutic problem: (i) per se because of the associated morbidity, mortality and the accompanying decrease of quality of life, (ii) as survival space for (residual) myeloma cells after primarily successful chemotherapy and subsequently necessary chemotherapeutic treatment, and (iii) the occurrence of bone lesions in asymptomatic patients is the most common cause for the initiation of treatment to avoid myeloma-induced fractures. Myeloma cells harbor a high median number of chromosomal aberrations and multiple changes in gene expression compared to normal bone marrow plasma cells leading to the aberrant production of survival, proliferation, pro-angiogenic and bone turnover influencing factors or the induction of those factors in the bone marrow microenvironment. This causes an imbalanced bone turnover in the sense of an increased number and activity of osteoclasts while bone formation by osteoblasts is almost completely suspended. Therapeutic approaches, systemically and locally therefore aim at stimulation of osteoblasts and inhibition of bone resorption.
Authors: Jens Hillengass; Kerstin Fechtner; Marc-André Weber; Tobias Bäuerle; Sofia Ayyaz; Christiane Heiss; Thomas Hielscher; Thomas M Moehler; Gerlinde Egerer; Kai Neben; Anthony D Ho; Hans-Ulrich Kauczor; Stefan Delorme; Hartmut Goldschmidt Journal: J Clin Oncol Date: 2010-02-22 Impact factor: 44.544
Authors: Dirk Hose; Thierry Rème; Thomas Hielscher; Jérôme Moreaux; Tobias Messner; Anja Seckinger; Axel Benner; John D Shaughnessy; Bart Barlogie; Yiming Zhou; Jens Hillengass; Uta Bertsch; Kai Neben; Thomas Möhler; Jean François Rossi; Anna Jauch; Bernard Klein; Hartmut Goldschmidt Journal: Haematologica Date: 2010-09-30 Impact factor: 9.941
Authors: E Terpos; E Kastritis; D Christoulas; M Gkotzamanidou; E Eleutherakis-Papaiakovou; N Kanellias; A Papatheodorou; M A Dimopoulos Journal: Ann Oncol Date: 2012-04-06 Impact factor: 32.976
Authors: Dirk Hose; Thierry Rème; Tobias Meissner; Jérôme Moreaux; Anja Seckinger; Joe Lewis; Vladimir Benes; Axel Benner; Michael Hundemer; Thomas Hielscher; John D Shaughnessy; Bart Barlogie; Kai Neben; Alwin Krämer; Jens Hillengass; Uta Bertsch; Anna Jauch; John De Vos; Jean-François Rossi; Thomas Möhler; Jonathon Blake; Jürgen Zimmermann; Bernard Klein; Hartmut Goldschmidt Journal: Blood Date: 2009-01-26 Impact factor: 22.113