TY - JOUR
T1 - Denosumab in postmenopausal women with osteoporosis and diabetes
T2 - Subgroup analysis of FREEDOM and FREEDOM extension
AU - Ferrari, Serge
AU - Eastell, Richard
AU - Napoli, Nicola
AU - Schwartz, Ann
AU - Hofbauer, Lorenz C.
AU - Chines, Arkadi
AU - Wang, Andrea
AU - Pannacciulli, Nico
AU - Cummings, Steven R.
N1 - Funding Information:
SF has received research support from Amgen , Agnovos , Alexion , and UCB and consulting honoraria from Amgen, Labatec, UCB Pharma, Alexion, and Agnovos all outside the submitted work. RE has received research grants from Alexion , Amgen , and Ultragenyx and consulting fees from ImmunoDiagnostic Systems, GlaxoSmithKline, and Amgen, all outside the submitted work. NN has received consulting fees from Amgen and MSD, all outside the submitted work. AS has received research grants from Hologic and consulting fees from Janssen Pharmaceuticals and Amgen, all outside the submitted work). LH has received research support from Amgen and Novartis and consulting fees from Alexion, Amgen, Novartis, Radius, Shire, and UCB, all outside the submitted work. AC, AW, and NP are all Amgen employees with stock options. SRC has received consulting fees from Amgen, outside the submitted work.
Funding Information:
This study was sponsored by Amgen Inc.
Funding Information:
The authors thank Hannah Greenwood, PhD, Stephanie Weng, PhD, and Fiona Woodward, PhD (Fishawack Communications Inc.), whose work was funded by Amgen Inc. , and Lisa Humphries, PhD ( Amgen Inc. ) for providing medical writing assistance. Additionally, the authors thank Shuang Huang, PhD (Amgen Inc.) for statistical support. Research on bone health in diabetes by SF, RE, NN, and LCH is supported by the European Union' s Horizon 2020 research and innovation program under the MARIE SKŁODOWSKA-CURIE grant agreement no. 860898 (FIDELIO).
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5
Y1 - 2020/5
N2 - Purpose: Diabetes and osteoporosis occur frequently in older adults and are both associated with increased fracture risk. Denosumab treatment reduced new vertebral, nonvertebral, and hip fractures over 3 years, with continued low fracture incidence for up to 10 years in postmenopausal women with osteoporosis. However, its effects in diabetic subjects with osteoporosis have not yet been investigated. Methods: Post hoc analysis of the 3-year, placebo-controlled FREEDOM study and 7-year Extension included postmenopausal women with osteoporosis and diabetes. Effects on BMD, vertebral, and nonvertebral fracture incidence were evaluated. Results: Of 7808 subjects in FREEDOM, 508 with diabetes received denosumab (n = 266) or placebo (n = 242). Among those, BMD increased significantly with denosumab versus placebo in FREEDOM, and continued to increase during the Extension in long-term (continuing denosumab) and crossover (placebo to denosumab) denosumab subjects. In FREEDOM, denosumab-treated subjects with diabetes had significantly lower new vertebral fracture rates (1.6%) versus placebo (8.0%) (RR: 0.20 [95% CI 0.07–0.61]; p = .001). Nonvertebral fracture incidence was higher with denosumab (11.7%) versus placebo (5.9%) (HR: 1.94 [95% CI 1.00–3.77]; p = .046), although there were fewer hip fractures with denosumab (World Health Organization, 2017 [1]) than placebo (4; nonsignificant). During the first 3 years in FREEDOM Extension, new vertebral and nonvertebral fracture incidences were low in long-term and crossover denosumab diabetic groups (≤6%), consistent with the overall Extension population; yearly nonvertebral fracture incidence was comparable to the FREEDOM placebo group. Conclusion: Denosumab significantly increased BMD and decreased vertebral fracture risk in subjects with osteoporosis and diabetes. No reduction in nonvertebral fractures was observed.
AB - Purpose: Diabetes and osteoporosis occur frequently in older adults and are both associated with increased fracture risk. Denosumab treatment reduced new vertebral, nonvertebral, and hip fractures over 3 years, with continued low fracture incidence for up to 10 years in postmenopausal women with osteoporosis. However, its effects in diabetic subjects with osteoporosis have not yet been investigated. Methods: Post hoc analysis of the 3-year, placebo-controlled FREEDOM study and 7-year Extension included postmenopausal women with osteoporosis and diabetes. Effects on BMD, vertebral, and nonvertebral fracture incidence were evaluated. Results: Of 7808 subjects in FREEDOM, 508 with diabetes received denosumab (n = 266) or placebo (n = 242). Among those, BMD increased significantly with denosumab versus placebo in FREEDOM, and continued to increase during the Extension in long-term (continuing denosumab) and crossover (placebo to denosumab) denosumab subjects. In FREEDOM, denosumab-treated subjects with diabetes had significantly lower new vertebral fracture rates (1.6%) versus placebo (8.0%) (RR: 0.20 [95% CI 0.07–0.61]; p = .001). Nonvertebral fracture incidence was higher with denosumab (11.7%) versus placebo (5.9%) (HR: 1.94 [95% CI 1.00–3.77]; p = .046), although there were fewer hip fractures with denosumab (World Health Organization, 2017 [1]) than placebo (4; nonsignificant). During the first 3 years in FREEDOM Extension, new vertebral and nonvertebral fracture incidences were low in long-term and crossover denosumab diabetic groups (≤6%), consistent with the overall Extension population; yearly nonvertebral fracture incidence was comparable to the FREEDOM placebo group. Conclusion: Denosumab significantly increased BMD and decreased vertebral fracture risk in subjects with osteoporosis and diabetes. No reduction in nonvertebral fractures was observed.
KW - Clinical trials
KW - Diseases and disorders of/related to bone osteoporosis
KW - Therapeutics antiresorptive
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U2 - 10.1016/j.bone.2020.115268
DO - 10.1016/j.bone.2020.115268
M3 - Article
C2 - 32058020
AN - SCOPUS:85079689143
VL - 134
JO - Bone
JF - Bone
SN - 8756-3282
M1 - 115268
ER -