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Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab: A Longitudinal Analysis From Baseline to 3 Months in the AVA Study.

  • Dempster, David W1, 2
  • Zhou, Hua1
  • Recker, Robert R3
  • Brown, Jacques P4
  • Recknor, Christopher P5
  • Lewiecki, E Michael6
  • Miller, Paul D7
  • Rao, Sudhaker D8
  • Kendler, David L9
  • Lindsay, Robert1, 2
  • Krege, John H10
  • Alam, Jahangir10
  • Taylor, Kathleen A11
  • Melby, Thomas E12
  • Ruff, Valerie A11
  • 1 Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA.
  • 2 Department of Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
  • 3 Department of Medicine, Division of Endocrinology, School of Medicine, Creighton University, Omaha, NE, USA.
  • 4 Rheumatology and Bone Diseases Research Group, CHU de Québec (CHUL), Research Centre and Department of Medicine, Laval University, Quebec City, Canada. , (Canada)
  • 5 United Osteoporosis Centers, Gainesville, GA, USA.
  • 6 New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA. , (Mexico)
  • 7 Department of Medicine, Colorado Center for Bone Research, Lakewood, CO, USA.
  • 8 Bone & Mineral Research Laboratory, Henry Ford Hospital, Detroit, MI, USA.
  • 9 Department of Medicine (Endocrinology), University of British Columbia, Vancouver, Canada. , (Canada)
  • 10 Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA. , (India)
  • 11 Musculoskeletal and Men's Health, Lilly USA LLC, Indianapolis, IN, USA. , (India)
  • 12 INC Research/inVentiv Health, Raleigh, NC, USA.
Published Article
Journal of Bone and Mineral Research
Wiley (John Wiley & Sons)
Publication Date
Feb 01, 2018
DOI: 10.1002/jbmr.3309
PMID: 29024120


There has been renewed interest of late in the role of modeling-based formation (MBF) during osteoporosis therapy. Here we describe early effects of an established anabolic (teriparatide) versus antiresorptive (denosumab) agent on remodeling-based formation (RBF), MBF, and overflow MBF (oMBF) in human transiliac bone biopsies. Postmenopausal women with osteoporosis received subcutaneous teriparatide (n = 33, 20 μg/d) or denosumab (n = 36, 60 mg once/6 months), open-label for 6 months at 7 US and Canadian sites. Subjects received double fluorochrome labeling at baseline and before biopsy at 3 months. Sites of bone formation were designated as MBF if the underlying cement line was smooth, RBF if scalloped, and oMBF if formed over smooth cement lines adjacent to scalloped reversal lines. At baseline, mean RBF/bone surface (BS), MBF/BS, and oMBF/BS were similar between the teriparatide and denosumab groups in each bone envelope assessed (cancellous, endocortical, periosteal). All types of formation significantly increased from baseline in the cancellous and endocortical envelopes (differences p < 0.001) with teriparatide (range of changes 2.9- to 21.9-fold), as did MBF in the periosteum (p < 0.001). In contrast, all types of formation were decreased or not significantly changed with denosumab, except MBF/BS in the cancellous envelope, which increased 2.5-fold (difference p = 0.048). These data highlight mechanistic differences between these agents: all 3 types of bone formation increased significantly with teriparatide, whereas formation was predominantly decreased or not significantly changed with denosumab, except for a slight increase in MBF/BS in the cancellous envelope. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

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