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

Barbara M. Misof, Paul Roschger, Daniela Gabriel, Eleftherios P. Paschalis, Erik F. Eriksen, Robert R. Recker, Jürg A. Gasser, Klaus Klaushofer

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The efficacy of 3 years of annual intravenous administration of zoledronic acid (ZOL) in reducing vertebral and nonvertebral 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 remodeling for the ZOL-treated 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 5 mg) and 70 treated with placebo, and all received adequate Ca and VitD supplementation. Comparison of ZOL-treated versus 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 highly 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 also revealed a statistically significant shift to higher Ca 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 a 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.

Original languageEnglish
Pages (from-to)442-448
Number of pages7
JournalJournal of Bone and Mineral Research
Volume28
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

zoledronic acid
Physiologic Calcification
Bone Matrix
Reference Values
Bone Density
Biopsy
Bone Remodeling
Placebos
Cancellous Bone
Postmenopausal Osteoporosis

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Annual intravenous zoledronic acid for three years increased cancellous bone matrix mineralization beyond normal values in the HORIZON biopsy cohort. / Misof, Barbara M.; Roschger, Paul; Gabriel, Daniela; Paschalis, Eleftherios P.; Eriksen, Erik F.; Recker, Robert R.; Gasser, Jürg A.; Klaushofer, Klaus.

In: Journal of Bone and Mineral Research, Vol. 28, No. 3, 03.2013, p. 442-448.

Research output: Contribution to journalArticle

Misof, Barbara M. ; Roschger, Paul ; Gabriel, Daniela ; Paschalis, Eleftherios P. ; Eriksen, Erik F. ; Recker, Robert R. ; Gasser, Jürg A. ; Klaushofer, Klaus. / Annual intravenous zoledronic acid for three years increased cancellous bone matrix mineralization beyond normal values in the HORIZON biopsy cohort. In: Journal of Bone and Mineral Research. 2013 ; Vol. 28, No. 3. pp. 442-448.
@article{5ed78ad55ab34c0a87ae56ba94b5cebb,
title = "Annual intravenous zoledronic acid for three years increased cancellous bone matrix mineralization beyond normal values in the HORIZON biopsy cohort",
abstract = "The efficacy of 3 years of annual intravenous administration of zoledronic acid (ZOL) in reducing vertebral and nonvertebral 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 remodeling for the ZOL-treated 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 5 mg) and 70 treated with placebo, and all received adequate Ca and VitD supplementation. Comparison of ZOL-treated versus 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 highly 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 also revealed a statistically significant shift to higher Ca 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 a 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.",
author = "Misof, {Barbara M.} and Paul Roschger and Daniela Gabriel and Paschalis, {Eleftherios P.} and Eriksen, {Erik F.} and Recker, {Robert R.} and Gasser, {J{\"u}rg A.} and Klaus Klaushofer",
year = "2013",
month = "3",
doi = "10.1002/jbmr.1780",
language = "English",
volume = "28",
pages = "442--448",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Annual intravenous zoledronic acid for three years increased cancellous bone matrix mineralization beyond normal values in the HORIZON biopsy cohort

AU - Misof, Barbara M.

AU - Roschger, Paul

AU - Gabriel, Daniela

AU - Paschalis, Eleftherios P.

AU - Eriksen, Erik F.

AU - Recker, Robert R.

AU - Gasser, Jürg A.

AU - Klaushofer, Klaus

PY - 2013/3

Y1 - 2013/3

N2 - The efficacy of 3 years of annual intravenous administration of zoledronic acid (ZOL) in reducing vertebral and nonvertebral 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 remodeling for the ZOL-treated 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 5 mg) and 70 treated with placebo, and all received adequate Ca and VitD supplementation. Comparison of ZOL-treated versus 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 highly 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 also revealed a statistically significant shift to higher Ca 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 a 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.

AB - The efficacy of 3 years of annual intravenous administration of zoledronic acid (ZOL) in reducing vertebral and nonvertebral 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 remodeling for the ZOL-treated 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 5 mg) and 70 treated with placebo, and all received adequate Ca and VitD supplementation. Comparison of ZOL-treated versus 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 highly 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 also revealed a statistically significant shift to higher Ca 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 a 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.

UR - http://www.scopus.com/inward/record.url?scp=84873975316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873975316&partnerID=8YFLogxK

U2 - 10.1002/jbmr.1780

DO - 10.1002/jbmr.1780

M3 - Article

VL - 28

SP - 442

EP - 448

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 3

ER -