Sanchita Agarwal1, Elizabeth Shane1, Thomas Lang2, Stephanie Shiau3, Mafo Kamanda-Kosseh1, Mariana Bucovsky1, Joan M Lappe4, Julie Stubby4, Robert R Recker4, Yizhong Hu5, Zexi Wang5, X Edward Guo5, Adi Cohen1. 1. Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA. 2. Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA. 3. Department of Biostatistics & Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA. 4. Department of Medicine, Creighton University Medical Center, Omaha, NE, USA. 5. Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Abstract
CONTEXT: Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in bone density, microstructure, and strength. OBJECTIVE: To define effects of treatment with teriparatide followed by denosumab on lumbar spine (LS) volumetric bone mineral density (vBMD) and stiffness by finite element analysis assessed on central quantitative computed tomography (cQCT) scans. DESIGN, SETTINGS, AND PARTICIPANTS: Ancillary analysis of baseline, post-teriparatide, and post-denosumab cQCT scans from a randomized trial of 41 women allocated to teriparatide (20 mcg daily; n = 28) or placebo (n = 11). After 6 months, those on teriparatide continued for 18 months, and those on placebo switched to teriparatide for 24 months. After completing teriparatide, 33 enrolled in a Phase 2B extension with denosumab (60 mg every 6 months) for 12 months. MAIN OUTCOME MEASURES: Primary outcomes were percentage change from baseline in LS trabecular vBMD and stiffness after teriparatide and between end of teriparatide and completing denosumab. Percentage change from baseline in LS trabecular vBMD and stiffness after sequential teriparatide and denosumab were secondary outcomes. FINDINGS: There were large increases (all Ps < 0.001) in trabecular vBMD (25%), other vBMD parameters, and stiffness (21%) after teriparatide. Statistically significant increases in trabecular vBMD (10%; P < 0.001) and other vBMD parameters (P = 0.03-0.001) were seen after denosumab, while stiffness increased by 7% (P = 0.068). Sequential teriparatide and denosumab led to highly significant (all Ps < 0.001) increases LS trabecular vBMD (43%), other vBMD parameters (15-31%), and stiffness (21%). CONCLUSIONS: The large and statistically significant increases in volumetric density and stiffness after sequential treatment with teriparatide followed by denosumab are encouraging and support use of this regimen in PreMenIOP.
CONTEXT: Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in bone density, microstructure, and strength. OBJECTIVE: To define effects of treatment with teriparatide followed by denosumab on lumbar spine (LS) volumetric bone mineral density (vBMD) and stiffness by finite element analysis assessed on central quantitative computed tomography (cQCT) scans. DESIGN, SETTINGS, AND PARTICIPANTS: Ancillary analysis of baseline, post-teriparatide, and post-denosumab cQCT scans from a randomized trial of 41 women allocated to teriparatide (20 mcg daily; n = 28) or placebo (n = 11). After 6 months, those on teriparatide continued for 18 months, and those on placebo switched to teriparatide for 24 months. After completing teriparatide, 33 enrolled in a Phase 2B extension with denosumab (60 mg every 6 months) for 12 months. MAIN OUTCOME MEASURES: Primary outcomes were percentage change from baseline in LS trabecular vBMD and stiffness after teriparatide and between end of teriparatide and completing denosumab. Percentage change from baseline in LS trabecular vBMD and stiffness after sequential teriparatide and denosumab were secondary outcomes. FINDINGS: There were large increases (all Ps < 0.001) in trabecular vBMD (25%), other vBMD parameters, and stiffness (21%) after teriparatide. Statistically significant increases in trabecular vBMD (10%; P < 0.001) and other vBMD parameters (P = 0.03-0.001) were seen after denosumab, while stiffness increased by 7% (P = 0.068). Sequential teriparatide and denosumab led to highly significant (all Ps < 0.001) increases LS trabecular vBMD (43%), other vBMD parameters (15-31%), and stiffness (21%). CONCLUSIONS: The large and statistically significant increases in volumetric density and stiffness after sequential treatment with teriparatide followed by denosumab are encouraging and support use of this regimen in PreMenIOP.
Authors: A Cohen; R R Recker; J Lappe; D W Dempster; S Cremers; D J McMahon; E M Stein; J Fleischer; C J Rosen; H Rogers; R B Staron; J Lemaster; E Shane Journal: Osteoporos Int Date: 2011-03-02 Impact factor: 4.507
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Authors: Claus-C Glüer; Fernando Marin; Johann D Ringe; Federico Hawkins; Rüdiger Möricke; Nikolaos Papaioannu; Parvis Farahmand; Salvatore Minisola; Guillermo Martínez; Joan M Nolla; Christopher Niedhart; Nuria Guañabens; Ranuccio Nuti; Emilio Martín-Mola; Friederike Thomasius; Georgios Kapetanos; Jaime Peña; Christian Graeff; Helmut Petto; Beatriz Sanz; Andreas Reisinger; Philippe K Zysset Journal: J Bone Miner Res Date: 2013-06 Impact factor: 6.741