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01.07.2014 | original article | Ausgabe 13-14/2014

Wiener klinische Wochenschrift 13-14/2014

Inverse correlation of carotid intima-media thickness with raloxifene serum levels in osteoporosis

Zeitschrift:
Wiener klinische Wochenschrift > Ausgabe 13-14/2014
Autoren:
Tina Trdan Lušin, Aleš Mrhar, Janja Marc, Jurij Trontelj, Andrej Zavratnik, Branka Žegura, Marija Pfeifer, PhD Assist. Prof. Barbara Ostanek

Summary

Background

Raloxifene is a selective oestrogen receptor modulator with effects on bone and breast cancer and cardiovascular disease risk. The aim of this study was to examine the influence of raloxifene treatment on surrogate markers of atherosclerosis and the correlation of these markers with raloxifene serum concentrations.

Methods

A prospective clinical trial on 53 postmenopausal osteoporotic women treated with raloxifene was performed. Surrogate markers of atherosclerosis (flow-mediated vasodilatation, glyceryltrinitrate-induced vasodilatation of the brachial artery, carotid intima-media thickness (c-IMT), inter-cell adhesion molecule-1, vascular-cell adhesion molecule-1 and E-selectin) were measured before and after 6 months of treatment. Serum concentrations of raloxifene and raloxifene metabolites were assessed after 12 months of treatment. The tested markers were correlated with measured serum concentrations of raloxifene species.

Results

Among the tested surrogate markers of atherosclerosis c-IMT, E-selectin and ICAM changed significantly during treatment. A negative correlation of the non-metabolized raloxifene serum levels with the percentage change of c-IMT during treatment (r = − 0.315, p = 0.048) was found. Likewise, the sum of the levels of three raloxifene metabolites, raloxifene-6-b-glucuronide (M1), raloxifene-4'-b-glucuronide (M2) and raloxifene-6,4'-diglucuronide (M3) in serum showed a negative correlation with the percentage change of c-IMT during treatment (r = − 0.375, p = 0.017). For the other tested parameters, no correlation with raloxifene serum levels was found.

Conclusions

To the best of our knowledge, this is the first study correlating raloxifene species serum concentrations with changes in the surrogate markers of atherosclerosis. A greater decrease of c-IMT in patients with higher raloxifene concentrations could contribute to a lower risk of cardiovascular events in these patients.

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