Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis

NCT ID: NCT01575834

Last Updated: 2024-08-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

7180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-15

Study Completion Date

2016-12-28

Brief Summary

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The purpose of this study is to determine if treatment with romosozumab is effective in preventing fractures in women with postmenopausal osteoporosis

Detailed Description

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Conditions

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Postmenopausal Osteoporosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Romosozumab

Participants received 210 mg romosozumab subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

Group Type EXPERIMENTAL

Romosozumab

Intervention Type DRUG

Administered by subcutaneous injection once a month (QM)

Denosumab

Intervention Type DRUG

Administered by subcutaneous injection once every 6 months (Q6M)

Placebo

Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered by subcutaneous injection once a month (QM)

Denosumab

Intervention Type DRUG

Administered by subcutaneous injection once every 6 months (Q6M)

Interventions

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Romosozumab

Administered by subcutaneous injection once a month (QM)

Intervention Type DRUG

Placebo

Administered by subcutaneous injection once a month (QM)

Intervention Type DRUG

Denosumab

Administered by subcutaneous injection once every 6 months (Q6M)

Intervention Type DRUG

Other Intervention Names

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AMG 785 EVENITY™ Prolia®

Eligibility Criteria

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Inclusion Criteria

\- Postmenopausal women with osteoporosis, defined as low bone mineral density (BMD T-score at the total hip or femoral neck of ≤ -2.50)

Exclusion Criteria

* BMD T-score of ≤ -3.50 at the total hip or femoral neck
* History of hip fracture
* Any severe or more than 2 moderate vertebral fractures, as assessed by the central imaging based on lateral spine x-rays
* Use of agents affecting bone metabolism
* History of metabolic or bone disease (except osteoporosis)
* Vitamin D insufficiency (vitamin D repletion and rescreening is permitted)
* Current hyper- or hypocalcemia
* Current, uncontrolled hyper- or hypothyroidism
* Current, uncontrolled hyper- or hypoparathyroidism
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Tucson, Arizona, United States

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Laguna Hills, California, United States

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Los Angeles, California, United States

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Sacramento, California, United States

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Santa Maria, California, United States

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Walnut Creek, California, United States

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Lakewood, Colorado, United States

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Leesburg, Florida, United States

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Palm Harbor, Florida, United States

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Plantation, Florida, United States

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Tampa, Florida, United States

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Gainesville, Georgia, United States

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New Orleans, Louisiana, United States

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Bethesda, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Albuquerque, New Mexico, United States

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Asheville, North Carolina, United States

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Fargo, North Dakota, United States

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Cincinnati, Ohio, United States

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Mayfield, Ohio, United States

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Duncansville, Pennsylvania, United States

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Denton, Texas, United States

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Richmond, Virginia, United States

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Madison, Wisconsin, United States

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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Córdoba, Córdoba Province, Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Maroubra, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Herston, Queensland, Australia

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Keswick, South Australia, Australia

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Footscray, Victoria, Australia

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Geelong, Victoria, Australia

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Heidelberg West, Victoria, Australia

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Nedlands, Western Australia, Australia

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Brussels, , Belgium

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Genk, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Lommel, , Belgium

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Yvoir, , Belgium

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Curitiba, Paraná, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Calgary, Alberta, Canada

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Vancouver, British Columbia, Canada

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Hamilton, Ontario, Canada

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Oakville, Ontario, Canada

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Lachine, Quebec, Canada

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Québec, Quebec, Canada

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Medellín, Antioquia, Colombia

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Barranquilla, Atlántico, Colombia

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Bogota, Cundinamarca, Colombia

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Bogota, Cundinamarca, Colombia

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Bogota, Cundinamarca, Colombia

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Bogota, Cundinamarca, Colombia

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Bogotá, , Colombia

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Brno, , Czechia

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České Budějovice, , Czechia

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Havlíčkův Brod, , Czechia

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Klatovy, , Czechia

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Ostrava-Trebovice, , Czechia

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Pardubice, , Czechia

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Pilsen, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Praha 11 - Chodov, , Czechia

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Uherské Hradiště, , Czechia

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Zlín, , Czechia

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Aalborg, , Denmark

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Århus C, , Denmark

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Ballerup Municipality, , Denmark

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Glostrup Municipality, , Denmark

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Hvidovre, , Denmark

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Odense, , Denmark

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Vejle, , Denmark

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Santo Domingo, Nacional, Dominican Republic

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Santo Domingo, Nacional, Dominican Republic

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Santo Domingo, , Dominican Republic

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Pärnu, , Estonia

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Tallinn, , Estonia

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Tartu, , Estonia

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Berlin, , Germany

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Bochum, , Germany

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Dresden, , Germany

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Dresden, , Germany

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Frankfurt am Main, , Germany

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Frankfurt am Main, , Germany

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Görlitz, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heinsberg, , Germany

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Hellersdorf, , Germany

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Leipzig, , Germany

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Magdeburg, , Germany

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Marburg, , Germany

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Schkeuditz, , Germany

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Békéscsaba, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Hévíz, , Hungary

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Szeged, , Hungary

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Zalaegerszeg, , Hungary

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Bangalore, Karnataka, India

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Mumbai, Maharashtra, India

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Pune, Maharashtra, India

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Jaipur, Rajasthan, India

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Chennai, Tamil Nadu, India

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Vellore, Tamil Nadu, India

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Anjyo-shi, Aichi-ken, Japan

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Urayasu-shi, Chiba, Japan

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Fukui-shi, Fukui, Japan

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Fukui-shi, Fukui, Japan

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Fukui-shi, Fukui, Japan

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Fukui-shi, Fukui, Japan

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Fukuoka, Fukuoka, Japan

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Fukutsu-shi, Fukuoka, Japan

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Kitakyushu-shi, Fukuoka, Japan

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Kurume-shi, Fukuoka, Japan

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Kurume-shi, Fukuoka, Japan

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Hiroshima, Hiroshima, Japan

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Chitose-shi, Hokkaido, Japan

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Ishikari-shi, Hokkaido, Japan

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Sunagawa-shi, Hokkaido, Japan

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Akashi-shi, Hyōgo, Japan

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Kako-gun, Hyōgo, Japan

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Toride-shi, Ibaraki, Japan

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Morioka, Iwate, Japan

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Takamatsu, Kagawa-ken, Japan

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Kirishima-shi, Kagoshima-ken, Japan

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Minamikyusyu-shi, Kagoshima-ken, Japan

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Atugi-shi, Kanagawa, Japan

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Sagamihara-shi, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Kumamoto, Kumamoto, Japan

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Sendai, Miyagi, Japan

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Chiisagata-gun, Nagano, Japan

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Matsumoto-shi, Nagano, Japan

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Matsumoto-shi, Nagano, Japan

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Ueda-shi, Nagano, Japan

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Ueda-shi, Nagano, Japan

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Bungoono-shi, Oita Prefecture, Japan

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Osaka, Osaka, Japan

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Takatsuki-shi, Osaka, Japan

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Saga, Saga-ken, Japan

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Fujimi-shi, Saitama, Japan

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Matsue, Shimane, Japan

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Fujinomiya-shi, Shizuoka, Japan

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Kikugawa-shi, Shizuoka, Japan

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Tokushima, Tokushima, Japan

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Hachioji-shi, Tokyo, Japan

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Kiyose-shi, Tokyo, Japan

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Minato-ku, Tokyo, Japan

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Ōta-ku, Tokyo, Japan

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Setagaya-ku, Tokyo, Japan

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Shinagawa-ku, Tokyo, Japan

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Shinagawa-ku, Tokyo, Japan

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Suginami-ku, Tokyo, Japan

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Suginami-ku, Tokyo, Japan

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Toshima-ku, Tokyo, Japan

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Kofu, Yamanashi, Japan

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Liepāja, , Latvia

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Riga, , Latvia

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Riga, , Latvia

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Kaunas, , Lithuania

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Kaunas, , Lithuania

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Klaipėda, , Lithuania

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Vilnius, , Lithuania

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Vilnius, , Lithuania

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Mexico City, Mexico City, Mexico

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Monterrey, Nuevo León, Mexico

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Ciudad Obregón, Sonora, Mexico

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Christchurch, , New Zealand

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Grafton, Auckland, , New Zealand

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Dabrowka Dopiewo, , Poland

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Elblag, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Świdnik, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Bucharest, , Romania

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Bucharest, , Romania

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Timișoara, , Romania

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Barcelona, Catalonia, Spain

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Pozuelo de Alarcón, Madrid, Spain

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Valencia, Valencia, Spain

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Madrid, , Spain

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Madrid, , Spain

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Bern, , Switzerland

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Fribourg, , Switzerland

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Geneva, , Switzerland

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Lausanne, , Switzerland

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Zurich, , Switzerland

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Zurich, , Switzerland

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Chorley, , United Kingdom

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Glasgow, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Northwood, , United Kingdom

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Reading, , United Kingdom

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Countries

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United States Argentina Australia Belgium Brazil Canada Colombia Czechia Denmark Dominican Republic Estonia Germany Hungary India Japan Latvia Lithuania Mexico New Zealand Poland Romania Spain Switzerland United Kingdom

References

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Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016 Oct 20;375(16):1532-1543. doi: 10.1056/NEJMoa1607948. Epub 2016 Sep 18.

Reference Type BACKGROUND
PMID: 27641143 (View on PubMed)

Cosman F, Crittenden DB, Ferrari S, Khan A, Lane NE, Lippuner K, Matsumoto T, Milmont CE, Libanati C, Grauer A. FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab. J Bone Miner Res. 2018 Jul;33(7):1219-1226. doi: 10.1002/jbmr.3427. Epub 2018 May 17.

Reference Type BACKGROUND
PMID: 29573473 (View on PubMed)

Chavassieux P, Chapurlat R, Portero-Muzy N, Roux JP, Garcia P, Brown JP, Libanati C, Boyce RW, Wang A, Grauer A. Bone-Forming and Antiresorptive Effects of Romosozumab in Postmenopausal Women With Osteoporosis: Bone Histomorphometry and Microcomputed Tomography Analysis After 2 and 12 Months of Treatment. J Bone Miner Res. 2019 Sep;34(9):1597-1608. doi: 10.1002/jbmr.3735. Epub 2019 Jun 24.

Reference Type BACKGROUND
PMID: 31233639 (View on PubMed)

Cosman F, Crittenden DB, Ferrari S, Lewiecki EM, Jaller-Raad J, Zerbini C, Milmont CE, Meisner PD, Libanati C, Grauer A. Romosozumab FRAME Study: A Post Hoc Analysis of the Role of Regional Background Fracture Risk on Nonvertebral Fracture Outcome. J Bone Miner Res. 2018 Aug;33(8):1407-1416. doi: 10.1002/jbmr.3439. Epub 2018 May 11.

Reference Type BACKGROUND
PMID: 29750828 (View on PubMed)

Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, Gielen E, Milmont CE, Libanati C, Grauer A. One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study. J Bone Miner Res. 2019 Mar;34(3):419-428. doi: 10.1002/jbmr.3622. Epub 2018 Dec 3.

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PMID: 30508316 (View on PubMed)

Miyauchi A, Dinavahi RV, Crittenden DB, Yang W, Maddox JC, Hamaya E, Nakamura Y, Libanati C, Grauer A, Shimauchi J. Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension. Arch Osteoporos. 2019 Jun 5;14(1):59. doi: 10.1007/s11657-019-0608-z.

Reference Type BACKGROUND
PMID: 31168657 (View on PubMed)

Miyauchi A, Hamaya E, Yang W, Nishi K, Libanati C, Tolman C, Shimauchi J. Romosozumab followed by denosumab in Japanese women with high fracture risk in the FRAME trial. J Bone Miner Metab. 2021 Mar;39(2):278-288. doi: 10.1007/s00774-020-01147-5. Epub 2020 Oct 15.

Reference Type BACKGROUND
PMID: 33057807 (View on PubMed)

McCloskey EV, Johansson H, Harvey NC, Lorentzon M, Shi Y, Kanis JA. Romosozumab efficacy on fracture outcomes is greater in patients at high baseline fracture risk: a post hoc analysis of the first year of the frame study. Osteoporos Int. 2021 Aug;32(8):1601-1608. doi: 10.1007/s00198-020-05815-0. Epub 2021 Feb 3.

Reference Type BACKGROUND
PMID: 33537844 (View on PubMed)

Eriksen EF, Chapurlat R, Boyce RW, Shi Y, Brown JP, Horlait S, Betah D, Libanati C, Chavassieux P. Modeling-Based Bone Formation After 2 Months of Romosozumab Treatment: Results From the FRAME Clinical Trial. J Bone Miner Res. 2022 Jan;37(1):36-40. doi: 10.1002/jbmr.4457. Epub 2021 Nov 19.

Reference Type BACKGROUND
PMID: 34633116 (View on PubMed)

Miller PD, Adachi JD, Albergaria BH, Cheung AM, Chines AA, Gielen E, Langdahl BL, Miyauchi A, Oates M, Reid IR, Santiago NR, Vanderkelen M, Wang Z, Yu Z. Efficacy and Safety of Romosozumab Among Postmenopausal Women With Osteoporosis and Mild-to-Moderate Chronic Kidney Disease. J Bone Miner Res. 2022 Aug;37(8):1437-1445. doi: 10.1002/jbmr.4563. Epub 2022 May 20.

Reference Type BACKGROUND
PMID: 35466448 (View on PubMed)

Takada J, Dinavahi R, Miyauchi A, Hamaya E, Hirama T, Libanati C, Nakamura Y, Milmont CE, Grauer A. Relationship between P1NP, a biochemical marker of bone turnover, and bone mineral density in patients transitioned from alendronate to romosozumab or teriparatide: a post hoc analysis of the STRUCTURE trial. J Bone Miner Metab. 2020 May;38(3):310-315. doi: 10.1007/s00774-019-01057-1. Epub 2019 Nov 9.

Reference Type BACKGROUND
PMID: 31707465 (View on PubMed)

Miyauchi A, Hamaya E, Nishi K, Tolman C, Shimauchi J. Efficacy and safety of romosozumab among Japanese postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. J Bone Miner Metab. 2022 Jul;40(4):677-687. doi: 10.1007/s00774-022-01332-8. Epub 2022 May 31.

Reference Type BACKGROUND
PMID: 35639174 (View on PubMed)

Eriksen EF, Boyce RW, Shi Y, Brown JP, Betah D, Libanati C, Oates M, Chapurlat R, Chavassieux P. Reconstruction of remodeling units reveals positive effects after 2 and 12 months of romosozumab treatment. J Bone Miner Res. 2024 Jul 23;39(6):729-736. doi: 10.1093/jbmr/zjae055.

Reference Type BACKGROUND
PMID: 38640512 (View on PubMed)

Lane NE, Betah D, Deignan C, Oates M, Wang Z, Timoshanko J, Khan AA, Binkley N. Effect of Romosozumab Treatment in Postmenopausal Women With Osteoporosis and Knee Osteoarthritis: Results From a Substudy of a Phase 3 Clinical Trial. ACR Open Rheumatol. 2024 Jan;6(1):43-51. doi: 10.1002/acr2.11619. Epub 2023 Nov 20.

Reference Type BACKGROUND
PMID: 37985218 (View on PubMed)

McClung MR, Betah D, Deignan C, Shi Y, Timoshanko J, Cosman F. Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk. Endocr Pract. 2023 Sep;29(9):716-722. doi: 10.1016/j.eprac.2023.06.011. Epub 2023 Jul 4.

Reference Type BACKGROUND
PMID: 37406858 (View on PubMed)

Cosman F, Oates M, Betah D, Timoshanko J, Wang Z, Ferrari S, McClung MR. Romosozumab followed by denosumab versus denosumab only: a post hoc analysis of FRAME and FRAME extension. J Bone Miner Res. 2024 Sep 2;39(9):1268-1277. doi: 10.1093/jbmr/zjae116.

Reference Type BACKGROUND
PMID: 39041711 (View on PubMed)

Lane J, Langdahl B, Stone M, Kurth A, Oates M, Timoshanko J, Wang Z, Libanati C, Cosman F. Romosozumab in patients who experienced an on-study fracture: post hoc analyses of the FRAME and ARCH phase 3 trials. Osteoporos Int. 2024 Jul;35(7):1195-1204. doi: 10.1007/s00198-024-07049-w. Epub 2024 Apr 4.

Reference Type DERIVED
PMID: 38573517 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2011-001456-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20070337

Identifier Type: -

Identifier Source: org_study_id

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