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Volume 155, Issue 5, Pages 247-255 (May 2010)


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Markers of bone remodeling and skeletal morbidity in patients with solid tumors metastatic to the skeleton receiving the biphosphonate zoledronic acid

Giannis MountziosaCorresponding Author Informationemail address, Evangelos Terposb, Konstantinos Syrigosc, Christos Papadimitrioud, Giorgos Papadopoulosa, Aristotelis Bamiasd, Myron Mavrikakisd, Meletios-Athanassios Dimopoulosd

Received 18 September 2009; received in revised form 20 December 2009; accepted 9 January 2010. published online 08 February 2010.

The molecular triad, which includes the receptor activator of nuclear factor kappa-B ligand (RANKL), its receptor RANK, and the endogenous soluble RANKL decoy receptor osteoprotegerin (OPG), has emerged as an important determinant of bone metabolism. We aimed to evaluate the effect of treatment with the biphosphonate zoledronic acid (ZA) on biochemical markers of bone remodeling and to detect possible correlations of markerlevel changes with skeletal morbidity and clinical outcomes in patients with solid tumors and osseous metastases. The following serum markers were measured at the onset of skeletal metastases and after 6 months of treatment with ZA (4 mg intravenously monthly) in 70 patients with breast (n = 30), lung (n = 18), or prostate (n = 22) cancer: RANKL, OPG, C-terminal cross-linking telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), bone-specific alkaline phosphatase (bALP), and osteopontin (OPN). Logistic regression models were applied to assess the correlation between marker-level changes and skeletal related events (SRE, primary endpoint), recurrence or progression, and death. Within a median follow-up of 32 months, 34 patients (48.6%) presented with at least 1 SRE and 48 patients (68.6%) relapsed. The RANKL/OPG ratio was upregulated in patients with breast and lung cancer, and it tended to decline after treatment with ZA, whereas prostate cancer patients presented with profound elevation of OPG only that persisted after treatment. CTX levels were significantly reduced after treatment in the whole study population (P = 0.003). None of the markers was able to predict skeletal morbidity or clinical outcomes independently of well-established prognostic clinical parameters.

a Department of Medical Oncology, 251 General Airforce Hospital, University of Athens, Athens, Greece

b Department of Biomedical Research, 251 General Airforce Hospital, University of Athens, Athens, Greece

c “Sotiria” Hospital, 3rd Department of Biomedical Research, University of Athens, Athens, Greece

d Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens, Athens, Greece, University of Athens, Athens, Greece

Corresponding Author InformationReprint requests: Giannis Mountzios, PhD, Department of Medical Oncology, Univeristy Hospital Alexandra, 251 General Airforce Hospital, 3 P. Kanellopoulou Avenue, PC 115 25 Athens, Greece

 Supported by a Translational Research Fellowship (to G.M.) from the European Society of Medical Oncology (ESMO).

PII: S1931-5244(10)00009-5

doi:10.1016/j.trsl.2010.01.002


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