Denosumab in postmenopausal women with osteoporosis and diabetes:​ subgroup analysis of FREEDOM and FREEDOM extension

Ferrari, Serge; Eastell, Richard; Napoli, Nicola; Schwartz, Ann; Hofbauer, Lorenz C.; Chines, Arkadi; Wang, Andrea; Pannacciulli, Nico; Cummings, Steven R.

Affiliations

¹Division of Bone Diseases, Geneva University Hospitals, Geneva, Switzerland

²Academic unit of Bone Metabolism, University of Sheffield, Sheffield, UK

³John T. Milliken Department of Medicine, Campus Bio-Medico, University of Rome, Rome, Italy

⁴Ospedale Galeazzi IRCCS, Milan, Italy

⁵School of Medicine, University of California San Francisco, San Francisco, CA, USA

⁶Center for Healthy Aging and Division of Endocrinology, Diabetes, and Bone Diseases, Technische Universität Dresden, Dresden, Germany

⁷Global Development, Amgen Inc., Thousand Oaks, CA, USA

⁸Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA

Abstract and keywords

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.

Keywords: Diseases and disorders of/related to bone osteoporosis; Clinical trials; Therapeutics antiresorptive

Links

DOI: 10.1016/j.bone.2020.115268

PubMed: 32058020

WoS: 000527850700009

History

Received: 2019-09-17

Revised: 2020-02-9

Accepted: 2020-02-9

Online: 2020-02-10

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Cited By (2)

Year	Entry
2020	Vilaca T, Schini M, Harnan S, Sutton A, Poku E, Allen IE, Cummings SR, Eastell R. The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: a systematic review and meta-analysis update. Bone. August 2020;137:115457.
2022	Eastell R, Vittinghoff E, Lui L-Y, Ewing SK, Schwartz AV, Bauer DC, Black DM, Bouxsein ML. Diabetes mellitus and the benefit of antiresorptive therapy on fracture risk. J Bone Miner Res. November 2022;37(11):2121-2131.