Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib

A Randomized Trial

Kim Brixen, Roland Chapurlat, Angela M Cheung, Tony M Keaveny, Thomas Fuerst, Klaus Engelke, Robert Recker, Bernard Dardzinski, Nadia Verbruggen, Shabana Ather, Elizabeth Rosenberg, Anne E de Papp

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Context:Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys.Objective:The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine.Design:This was a randomized, double-blind, 2-year trial.Setting:The study was conducted at a private or institutional practice.Participants:Participants included 214 postmenopausal women with low areal BMD.Intervention:The intervention included odanacatib 50 mg or placebo weekly.Main Outcome Measures:Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured.Results:Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P <.001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P <.001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P <.001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P <.001 at 24 months). Adverse experiences were similar between groups.Conclusions:Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.
OriginalsprogEngelsk
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind98
Udgave nummer2
Sider (fra-til)571-580
ISSN0021-972X
DOI
StatusUdgivet - 21. jan. 2013

Fingeraftryk

Bone Density
Placebos
Hip
Osteogenesis
Institutional Practice
Cathepsin K
Compressive Strength
Procollagen
Finite Element Analysis
Private Practice
Femur Neck
Collagen Type I
X-Rays
Outcome Assessment (Health Care)
Peptides

Citer dette

Brixen, Kim ; Chapurlat, Roland ; Cheung, Angela M ; Keaveny, Tony M ; Fuerst, Thomas ; Engelke, Klaus ; Recker, Robert ; Dardzinski, Bernard ; Verbruggen, Nadia ; Ather, Shabana ; Rosenberg, Elizabeth ; de Papp, Anne E. / Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib : A Randomized Trial. I: Journal of Clinical Endocrinology and Metabolism. 2013 ; Bind 98, Nr. 2. s. 571-580.
@article{b7971d5a987340d7b4e0cde6301153ac,
title = "Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib: A Randomized Trial",
abstract = "Context:Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys.Objective:The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine.Design:This was a randomized, double-blind, 2-year trial.Setting:The study was conducted at a private or institutional practice.Participants:Participants included 214 postmenopausal women with low areal BMD.Intervention:The intervention included odanacatib 50 mg or placebo weekly.Main Outcome Measures:Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured.Results:Year 1 lumbar spine areal BMD percent change from baseline was 3.5{\%} greater with odanacatib than placebo (P <.001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P <.001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P <.001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P <.001 at 24 months). Adverse experiences were similar between groups.Conclusions:Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.",
author = "Kim Brixen and Roland Chapurlat and Cheung, {Angela M} and Keaveny, {Tony M} and Thomas Fuerst and Klaus Engelke and Robert Recker and Bernard Dardzinski and Nadia Verbruggen and Shabana Ather and Elizabeth Rosenberg and {de Papp}, {Anne E}",
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day = "21",
doi = "10.1210/jc.2012-2972",
language = "English",
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pages = "571--580",
journal = "Journal of Clinical Endocrinology and Metabolism",
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Brixen, K, Chapurlat, R, Cheung, AM, Keaveny, TM, Fuerst, T, Engelke, K, Recker, R, Dardzinski, B, Verbruggen, N, Ather, S, Rosenberg, E & de Papp, AE 2013, 'Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib: A Randomized Trial', Journal of Clinical Endocrinology and Metabolism, bind 98, nr. 2, s. 571-580. https://doi.org/10.1210/jc.2012-2972

Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib : A Randomized Trial. / Brixen, Kim; Chapurlat, Roland; Cheung, Angela M; Keaveny, Tony M; Fuerst, Thomas; Engelke, Klaus; Recker, Robert; Dardzinski, Bernard; Verbruggen, Nadia; Ather, Shabana; Rosenberg, Elizabeth; de Papp, Anne E.

I: Journal of Clinical Endocrinology and Metabolism, Bind 98, Nr. 2, 21.01.2013, s. 571-580.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib

T2 - A Randomized Trial

AU - Brixen, Kim

AU - Chapurlat, Roland

AU - Cheung, Angela M

AU - Keaveny, Tony M

AU - Fuerst, Thomas

AU - Engelke, Klaus

AU - Recker, Robert

AU - Dardzinski, Bernard

AU - Verbruggen, Nadia

AU - Ather, Shabana

AU - Rosenberg, Elizabeth

AU - de Papp, Anne E

PY - 2013/1/21

Y1 - 2013/1/21

N2 - Context:Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys.Objective:The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine.Design:This was a randomized, double-blind, 2-year trial.Setting:The study was conducted at a private or institutional practice.Participants:Participants included 214 postmenopausal women with low areal BMD.Intervention:The intervention included odanacatib 50 mg or placebo weekly.Main Outcome Measures:Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured.Results:Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P <.001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P <.001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P <.001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P <.001 at 24 months). Adverse experiences were similar between groups.Conclusions:Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.

AB - Context:Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys.Objective:The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine.Design:This was a randomized, double-blind, 2-year trial.Setting:The study was conducted at a private or institutional practice.Participants:Participants included 214 postmenopausal women with low areal BMD.Intervention:The intervention included odanacatib 50 mg or placebo weekly.Main Outcome Measures:Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured.Results:Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P <.001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P <.001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P <.001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P <.001 at 24 months). Adverse experiences were similar between groups.Conclusions:Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.

U2 - 10.1210/jc.2012-2972

DO - 10.1210/jc.2012-2972

M3 - Journal article

VL - 98

SP - 571

EP - 580

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -