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Annual intraveneous zoledronic acid for three years increased cancellous bone matrix mineralization beyond normal values in the HORIZON biopsy cohort

Misof, Barbara M and Roschger, Paul and Paschalis, Eleftherios P and Eriksen, Erik F and Recker, Robert R and Gasser, Juerg Andreas and Klaushofer, Klaus (2013) Annual intraveneous zoledronic acid for three years increased cancellous bone matrix mineralization beyond normal values in the HORIZON biopsy cohort. Journal of Bone and Mineral Research.

Abstract

The efficacy of 3 years’ annual intravenous administration of zoledronic acid (ZOL) in reducing vertebral and non-vertebral fractures in postmenopausal osteoporosis has been shown by the HORIZON pivotal fracture trial. Histomorphometric analysis of transiliac bone biopsies from the HORIZON participants revealed significantly improved trabecular architecture and reduced bone remodelling for the ZOL versus placebo treated patients. The aim of our study was to evaluate the cancellous and cortical bone mineralization density distribution (BMDD) in these biopsies by quantitative backscattered electron imaging (qBEI). The study cohort comprised 82 patients on active treatment (ZOL, yearly doses of 5mg), 70 treated with placebo and all received adequate Ca and VitD supplementation. Comparison of ZOL vs. placebo treated cancellous (Cn.) and cortical (Ct.) BMDD derived variables resulted in significantly higher average (Cn.CaMean +3.2%, Ct.CaMean +2.7%) and mode calcium concentrations (Cn.CaPeak +2.1%. Ct.CaPeak +1.5%), increased percentages of high mineralized bone areas (Cn.CaHigh +64%, Ct.CaHigh +31%), lower heterogeneity of mineralization (Cn.CaWidth -14%, Ct.CaWidth -13%), and decreased percentages of low mineralized bone areas (Cn.CaLow -22%, Ct.CaLow -26%) versus placebo (all p<0.001). Cn. BMDD from the patients on active treatment revealed also a statistically significant shift to higher calcium concentrations when compared to a historical normal reference BMDD. These differences in BMDD from ZOL patients compared to the other groups were in line with the correlation of BMDD variables with previously determined cancellous mineralizing surface per bone surface (Cn. MS/BS, a primary histomorphometric index for bone turnover), showing that those with lower Cn.MS/BS had higher degree of bone matrix mineralization. However, the differences in BMDD variables between the study groups remained when adjusted for Cn. MS/BS suggesting that other factors in addition to reduced bone turnover might contribute to the higher bone matrix mineralization after ZOL treatment.

Item Type: Article
Keywords: zoledronic acid, HORIZON pivotal fracture trial, bone mineralization density distribution, quantitative backscattered electron imaging (qBEI)
Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/7479

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