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Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) are regulators of bone remodeling, but are also considered to play important roles in coronary artery disease (CAD). This study evaluated potential associations of soluble (s) RANKL and OPG with atherosclerosis-relevant cytokines. Blood was collected from 414 individuals who presented to our hospital with intermediate likelihood for CAD for further examination. Plasma concentrations of total sRANKL, OPG, and 20 cytokines were measured using sandwich-type enzyme-linked immunoassays (ELISAs; OPG and sRANKL) and Luminex laser-based fluorescence analysis and correlated with each other. The plasma levels of interferon-γ (IFN-γ) and the T-helper cell 2 cytokines interleukin-4 (IL-4) and IL-13 showed a positive correlation with sRANKL. The association with sRANKL levels was negative for IFN-γ-induced protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1). The strongest independent association with sRANKL in multivariable analyses was found for IFN-γ (positive) and IP-10 (negative), while IL-13 showed a positive and independent association with OPG plasma levels. OPG and sRANKL plasma levels correlate strongly and independently with specific circulating atherosclerosis-related cytokines in patients with intermediate cardiovascular risk. [ABSTRACT FROM AUTHOR]

Osteolytic bone disease is the most common complication of multiple myeloma, resulting in skeletal-related events (SREs) that cause significant morbidity. Bone destruction in myeloma is due to an increased activity of osteoclasts coupled with suppressed bone formation by osteoblasts. Currently, bisphosphonates are the mainstay of the treatment of myeloma bone disease. Zoledronic acid and pamidronate have shown similar efficacy in reducing SREs in a randomized study in the conventional chemotherapy era. However, in a recent study (the Myeloma-IX trial of the UK Medical Research Council, MRC), zoledronic acid was found to be superior to clodronate in reducing SREs, but also it produced a survival advantage of approximately 10 months in patients with bone disease at baseline. During recent years, novel agents targeting bone have been used in myeloma. This review focuses on the established therapy of myeloma bone disease and also on recent advances in treatment that take advantage of the better understanding of the pathophysiology of bone disease. [ABSTRACT FROM AUTHOR]

The aim of this study was the evaluation of the effect of intermediate doses of thalidomide with dexamethasone (Thal/Dex) on disease course and bone disease in patients with refractory/relapsed myeloma who were under zoledronic acid therapy. We studied 35 patients, who received thalidomide at a dose of 200 mg/daily. We measured, pre-, 3 and 6 months post-treatment soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG), osteopontin (OPN), markers of bone resorption and formation. Before treatment, patients had increased levels of sRANKL/OPG ratio, bone resorption markers and OPN, while they had suppressed bone formation. The pretreatment sRANKL/OPG ratio correlated with the extent of bone disease. Thal/Dex administration resulted in a significant reduction of sRANKL/OPG ratio, and bone resorption. Bone formation, OPG and OPN did not show any alteration. Changes of sRANKL/OPG ratio correlated with changes of bone resorption markers. Thal/Dex was given for a median time of 10 months and the median follow-up period was 22 months. The response rate was 65.7%. The median survival was 19.5 months. β2-microglobulin, type of response and International Staging System predicted for survival. These results suggest that the combination of intermediate dose of Thal/Dex is effective in patients with refractory/relapsed myeloma and improves abnormal bone remodeling through the reduction of sRANKL/OPG ratio.Leukemia (2005) 19, 1969–1976. doi:10.1038/sj.leu.2403890; published online 4 August 2005 [ABSTRACT FROM AUTHOR]