FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab

Felicia Cosman, Daria B. Crittenden, Serge Ferrari, Aliya Khan, Nancy E Lane, Kurt Lippuner, Toshio Matsumoto, Cassandra E. Milmont, Cesar Libanati, Andreas Grauer

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210mgs.c. or placebo once monthly for 12 months, followed by denosumab 60mgs.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Here, we further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n=3591 placebo, n=3589 romosozumab), most romosozumab-treated patients experienced ≥3% gains in BMD from baseline at month 12 (spine, 96%; hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81% relative reduction; p<0.001), with fewer fractures consistently observed across other fracture categories. The data support the clinical benefit of rebuilding the skeletal foundation with romosozumab before transitioning to antiresorptive therapy.

Original languageEnglish (US)
JournalJournal of Bone and Mineral Research
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Bone and Bones
Placebos
Hip
Spine
Fracture Fixation
Osteoporosis
AMG 785
Denosumab
Postmenopausal Osteoporosis
Risk Reduction Behavior
Bone Resorption
Osteogenesis
Incidence

Keywords

  • ANABOLICS
  • FRACTURE RISK ASSESSMENT
  • OSTEOPOROSIS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

FRAME Study : The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab. / Cosman, Felicia; Crittenden, Daria B.; Ferrari, Serge; Khan, Aliya; Lane, Nancy E; Lippuner, Kurt; Matsumoto, Toshio; Milmont, Cassandra E.; Libanati, Cesar; Grauer, Andreas.

In: Journal of Bone and Mineral Research, 01.01.2018.

Research output: Contribution to journalArticle

Cosman, Felicia ; Crittenden, Daria B. ; Ferrari, Serge ; Khan, Aliya ; Lane, Nancy E ; Lippuner, Kurt ; Matsumoto, Toshio ; Milmont, Cassandra E. ; Libanati, Cesar ; Grauer, Andreas. / FRAME Study : The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab. In: Journal of Bone and Mineral Research. 2018.
@article{27d992ca8716467b9ded09f1e2b3c4b7,
title = "FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab",
abstract = "Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210mgs.c. or placebo once monthly for 12 months, followed by denosumab 60mgs.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13{\%} and 7{\%}, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Here, we further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n=3591 placebo, n=3589 romosozumab), most romosozumab-treated patients experienced ≥3{\%} gains in BMD from baseline at month 12 (spine, 96{\%}; hip, 78{\%}) compared with placebo (spine, 22{\%}; hip, 16{\%}). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81{\%} relative reduction; p<0.001), with fewer fractures consistently observed across other fracture categories. The data support the clinical benefit of rebuilding the skeletal foundation with romosozumab before transitioning to antiresorptive therapy.",
keywords = "ANABOLICS, FRACTURE RISK ASSESSMENT, OSTEOPOROSIS",
author = "Felicia Cosman and Crittenden, {Daria B.} and Serge Ferrari and Aliya Khan and Lane, {Nancy E} and Kurt Lippuner and Toshio Matsumoto and Milmont, {Cassandra E.} and Cesar Libanati and Andreas Grauer",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/jbmr.3427",
language = "English (US)",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - FRAME Study

T2 - The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab

AU - Cosman, Felicia

AU - Crittenden, Daria B.

AU - Ferrari, Serge

AU - Khan, Aliya

AU - Lane, Nancy E

AU - Lippuner, Kurt

AU - Matsumoto, Toshio

AU - Milmont, Cassandra E.

AU - Libanati, Cesar

AU - Grauer, Andreas

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210mgs.c. or placebo once monthly for 12 months, followed by denosumab 60mgs.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Here, we further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n=3591 placebo, n=3589 romosozumab), most romosozumab-treated patients experienced ≥3% gains in BMD from baseline at month 12 (spine, 96%; hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81% relative reduction; p<0.001), with fewer fractures consistently observed across other fracture categories. The data support the clinical benefit of rebuilding the skeletal foundation with romosozumab before transitioning to antiresorptive therapy.

AB - Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210mgs.c. or placebo once monthly for 12 months, followed by denosumab 60mgs.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Here, we further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n=3591 placebo, n=3589 romosozumab), most romosozumab-treated patients experienced ≥3% gains in BMD from baseline at month 12 (spine, 96%; hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81% relative reduction; p<0.001), with fewer fractures consistently observed across other fracture categories. The data support the clinical benefit of rebuilding the skeletal foundation with romosozumab before transitioning to antiresorptive therapy.

KW - ANABOLICS

KW - FRACTURE RISK ASSESSMENT

KW - OSTEOPOROSIS

UR - http://www.scopus.com/inward/record.url?scp=85047490676&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047490676&partnerID=8YFLogxK

U2 - 10.1002/jbmr.3427

DO - 10.1002/jbmr.3427

M3 - Article

AN - SCOPUS:85047490676

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

ER -