Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease

Seidel, Carina; Hjertner, Øyvind; Abildgaard, Niels; Heickendorff, Lene; Hjorth, Martin; Westin, Jan; Nielsen, Johan Lanng; Hjorth‐Hansen, Henrik; Waage, Anders; Sundan, Anders; Børset, Magne

doi:10.1182/blood.v98.7.2269

Cited by 156 publications

(97 citation statements)

References 23 publications

(13 reference statements)

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“…In patients with multiple myeloma, the ratio of RANKL and OPG has been shown to be markedly dysregulated, with an increase in RANKL expression, and a concomitant decrease in OPG expression and serum concentration (20)(21)(22)(23)(24) An increase in the serum RANKL:OPG ratio has been demonstrated in patients with multiple myeloma, which correlates with both bone disease and survival (25). There is evidence to support both an increase in RANKL expression by bone marrow stromal cells and osteoblasts (20)(21)(22), and also for expression of RANKL by myeloma cells (26,27).…”

Section: The Rank/rankl/opg Systemmentioning

confidence: 99%

The pathogenesis of the bone disease of multiple myeloma

Edwards

Zhuang

Mundy

2008

Bone

147

120

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Multiple myeloma is a fatal hematologic malignancy associated with clonal expansion of malignant plasma cells within the bone marrow and the development of a destructive osteolytic bone disease. The principal cellular mechanisms involved in the development of myeloma bone disease are an increase in osteoclastic bone resorption, and a reduction in bone formation. Myeloma cells are found in close association with sites of active bone resorption, and the interactions between myeloma cells, and other cells within the specialized bone marrow microenvironment are essential, both for tumor growth and the development of myeloma bone disease. This review discusses the many different factors which have been implicated in myeloma bone disease, including the evidence for their role in myeloma and subsequent therapeutic implications.

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Section: The Rank/rankl/opg Systemmentioning

confidence: 99%

The pathogenesis of the bone disease of multiple myeloma

Edwards

Zhuang

Mundy

2008

Bone

147

120

View full text Add to dashboard Cite

show abstract

“…41 Further enhancing the effects of increased RANKL in myeloma is the decreased production of OPG by marrow stromal cells via inhibition of osteoblast differentiation, decreased transcription of OPG and degradation of OPG by myeloma cell endocytosis of the OPG bound to CD138 (syndecan-1). 42,43 Thus, the ratio of RANKL to OPG in myeloma patients is markedly increased and drives osteoclastogenesis. Additionally, the ratio of RANKL to OPG, detectable in the sera from myeloma patients, impacts prognosis.…”

Section: Factors Driving Osteoclast Formation and Activity In Mmbdmentioning

confidence: 99%

Mechanisms of multiple myeloma bone disease

Galson¹,

Silbermann²,

Roodman³

2012

BoneKEy Reports

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Multiple myeloma is the second most common hematological malignancy and the most frequent cancer to involve the skeleton. Multiple myeloma bone disease (MMBD) is characterized by abnormal bone remodeling with dysfunction of both bone resorption and bone formation, and thus can be used as a paradigm for other inflammatory bone diseases, and the regulation of osteoclasts and osteoblasts in malignancy. Studies of MMBD have identified novel regulators that increase osteoclastogenesis and osteoclast function, repress osteoblast differentiation, increase angiogenesis, or permanently alter stromal cells. This review will discuss the current understanding of mechanisms of osteoclast and osteoblast regulation in MMBD, and therapeutic approaches currently in use and under development that target mediators of bone destruction and blockade of bone formation for myeloma patients, including new anabolic therapies.

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“…6 Evidence suggests that the increase in osteoclast activity in myeloma is due to an imbalance in the ratio of RANKL to OPG. RANKL expression is increased in bone marrow stroma cells, 7,8 and OPG is reduced in the bone marrow 8 and serum 9 of patients with myeloma. MIP-1a is an OAF produced directly by MM cells that induces osteoclast formation in human bone marrow cultures and its expression is elevated in the bone marrow of MM patients compared to healthy controls.…”

Section: Introductionmentioning

confidence: 99%

A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer

et al. 2007

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We describe a new model of myeloma bone disease in which b 2 m NOD/SCID mice injected with KMS-12-BM cells develop medullary disease after tail vein administration. Micro-computed tomography analysis demonstrated significant bone loss in the tibiae and vertebrae of diseased animals compared to controls, with loss of cortical bone (Po0.01), as well as trabecular bone volume, thickness and number (Po0.05 for all). Bone marrow of diseased animals demonstrated an increase in osteoclasts (Po0.01) and reduction in osteoblasts (Po0.01) compared to control animals. Both bone loss and osteoclast increase correlated with the degree of disease involvement. Mesenchymal stem cells (MSCs) were lentivirally transduced to express human osteoprotegerin (hOPG). Systemic administration of OPG expressing MSC reduced osteoclast activation (Po0.01) and trabecular bone loss in the vertebrae (Po0.05) and tibiae of diseased animals, to levels comparable to non-diseased controls. Because of its predominantly medullary involvement and quantifiable parameters of bone disease, the KMS-12-BM xenogeneic model provides unique opportunities to test therapies targeted at the bone marrow microenvironment.

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Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease

Cited by 156 publications

References 23 publications

The pathogenesis of the bone disease of multiple myeloma

The pathogenesis of the bone disease of multiple myeloma

Mechanisms of multiple myeloma bone disease

A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer

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