Soluble receptor activator of nuclear factor κB ligand–osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index

Terpos, Evangelos; Szydlo, Richard; Apperley, Jane F.; Hatjiharissi, Evdoxia; Politou, Marianna; Meletis, John; Viniou, Nora; Yataganas, Xenophon; Goldman, John M.; Rahemtulla, Amin

doi:10.1182/blood-2003-02-0380

Cited by 384 publications

(269 citation statements)

References 26 publications

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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

152

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

152

120

View full text Add to dashboard Cite

show abstract

“…Therefore, for identifying those patients at risk for early death and for selecting appropriate surgical interventions if longer survival is expected, it would be extremely valuable for orthopedic surgeons to find a marker of disease aggressiveness at the time of surgery that is easy to asses. In addition to the prognostic value of baseline biological markers including high levels of b2-microglobulin (B2-M), lactate dehydrogenase (LDH), and serum albumin (Bataille et al, 1992), elevations of serum C-reactive protein (CRP) have been consistently associated with a poor prognosis in myeloma (Tienhaara et al, 1994;Kaneko et al, 2002;Terpos et al, 2003). Several studies regarding the role of preoperative CRP as a predictive indicator for the malignant potential and prognosis in various other cancers have been published (Nozoe et al, 1998;Nakanishi et al, 2002;Shimada et al, 2003;Hashimoto et al, 2005).…”

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confidence: 99%

Preoperative elevation of serum C – reactive protein is predictive for prognosis in myeloma bone disease after surgery

et al. 2006

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We investigated whether preoperative levels of serum C-reactive protein (CRP) and its correlation with tumour clinicopathological findings adds prognostic information beyond the time of diagnosis in patients with myeloma bone disease (MM) to facilitate the surgical decision-making process. Six hundred and fifty-eight myeloma patients were evaluated retrospectively for surgery. Clinicopathological variables of patients who underwent surgery (n ¼ 71) were compared between patients with preoperative CRP X6 mg l À1 and those with CRP o6 mg l À1 . Univariate and multivariate analyses were performed to identify prognostic factors after surgery. Patients with an increase of CRP prior to surgery showed inferior survival compared to patients with normal levels. Patients with normal CRP levels at diagnosis but elevations prior to surgery do seem to have a similar unfavourable overall survival (OS) than patients with an increase both, at diagnosis and at surgery. Conversely, patients with normal CRP levels prior to surgery still have the best OS, irrespective of their basic values. Multivariate analysis revealed preoperative CRP levels above 6 mg l À1 Lactate dehydrogenase (LDH) above normal, and osteolyses in long weight bearing bones as independent predictors of survival. These findings suggest that in patients with MM serum levels of CRP increase during disease activity and might be significantly correlated with specific disease characteristics including adverse prognostic features such as osteolyses in long weight bearing bones. Thus, preoperative elevated CRP serum levels might be considered as independent predictor of prognosis and could provide additional prognostic information for the risk stratification before surgical treatment in patients with myeloma bone disease.

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“…19 A recent study showed that in newly diagnosed multiple myeloma patients, RANKL levels, and more particularly the OPG-to-RANKL ratio, correlated closely to the amount of metastatic osteolysis, and were found to be an independent predictor of life expectancy. 20 In this study, we aimed to investigate whether circulating levels of OPG, RANKL and their ratio are associated to the presence of osteolytic lesions in advanced neuroblastoma, as well as whether they provide additional information on the severity and the prognosis of disease.…”

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confidence: 99%

Plasma levels of receptor activator of nuclear factor‐κB ligand and osteoprotegerin in patients with neuroblastoma

Granchi

Garaventa

Amato

et al. 2006

Intl Journal of Cancer

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Earlier reports showed that the balance between receptor activator of nuclear factor-jB ligand (RANKL) and its decoy-receptor osteoprotegerin (OPG) plays an important role in the pathogenesis of metastatic osteolysis induced by neuroblastoma cells. In this study, we investigated whether circulating levels of OPG, RANKL and their ratio were associated to the presence of osteolytic lesions in advanced neuroblastoma, as well as whether they provided additional information on the severity and prognosis of the disease. Plasma levels of RANKL and OPG were measured in 54 newly diagnosed neuroblastomas; 27 of them showed metastatic disease (stage IV), including 19 bone dissemination. Thirty-five children who were admitted to the pediatric department for minor surgical problems served as control group. OPG was significantly lower in all patients compared with controls, while RANKL levels were significantly increased in advanced neuroblastoma. OPG-to-RANKL ratio decreased in stage-IV patients, and particularly in those who had bone metastases. The diagnostic accuracy of the OPG-to-RANKL ratio in discriminating the presence of osteolytic lesions was not confirmed statistically. OPG correlated significantly with other prognostic factors, namely, ferritin and neurone-specific enolase. In addition, an inverse relationship was found between OPG and event-free survival, and it was more significant in patients who had bone metastasis. This pilot study confirms that the production of OPG and RANKL is disregulated in neuroblastoma. Although the OPG-to-RANKL ratio does not have a predictive value in detecting bone metastasis, the measurement of the previously mentioned markers could be useful in decisions regarding the use of adjuvant therapies. ' 2006 Wiley-Liss, Inc.

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Soluble receptor activator of nuclear factor κB ligand–osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index

Cited by 384 publications

References 26 publications

The pathogenesis of the bone disease of multiple myeloma

The pathogenesis of the bone disease of multiple myeloma

Preoperative elevation of serum C – reactive protein is predictive for prognosis in myeloma bone disease after surgery

Plasma levels of receptor activator of nuclear factor‐κB ligand and osteoprotegerin in patients with neuroblastoma

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