Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab

A Longitudinal Analysis From Baseline to 3 Months in the AVA Study

David W. Dempster, Hua Zhou, Robert R. Recker, Jacques P. Brown, Christopher P. Recknor, E. Michael Lewiecki, Paul D. Miller, Sudhaker D. Rao, David L. Kendler, Robert Lindsay, John H. Krege, Jahangir Alam, Kathleen A. Taylor, Thomas E. Melby, Valerie A. Ruff

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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, 20μg/d) or denosumab (n=36, 60mg 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.

Original languageEnglish (US)
JournalJournal of Bone and Mineral Research
DOIs
StateAccepted/In press - Jan 1 2017

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Teriparatide
Osteogenesis
Bone and Bones
Osteoporosis
Bone Density Conservation Agents
Biopsy
Periosteum
Fluorescent Dyes
Denosumab

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab : A Longitudinal Analysis From Baseline to 3 Months in the AVA Study. / Dempster, David W.; Zhou, Hua; Recker, Robert R.; Brown, Jacques P.; Recknor, Christopher P.; Lewiecki, E. Michael; Miller, Paul D.; Rao, Sudhaker D.; Kendler, David L.; Lindsay, Robert; Krege, John H.; Alam, Jahangir; Taylor, Kathleen A.; Melby, Thomas E.; Ruff, Valerie A.

In: Journal of Bone and Mineral Research, 01.01.2017.

Research output: Contribution to journalArticle

Dempster, DW, Zhou, H, Recker, RR, Brown, JP, Recknor, CP, Lewiecki, EM, Miller, PD, Rao, SD, Kendler, DL, Lindsay, R, Krege, JH, Alam, J, Taylor, KA, Melby, TE & Ruff, VA 2017, 'Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab: A Longitudinal Analysis From Baseline to 3 Months in the AVA Study', Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.3309
Dempster, David W. ; Zhou, Hua ; Recker, Robert R. ; Brown, Jacques P. ; Recknor, Christopher P. ; Lewiecki, E. Michael ; Miller, Paul D. ; Rao, Sudhaker D. ; Kendler, David L. ; Lindsay, Robert ; Krege, John H. ; Alam, Jahangir ; Taylor, Kathleen A. ; Melby, Thomas E. ; Ruff, Valerie A. / Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab : A Longitudinal Analysis From Baseline to 3 Months in the AVA Study. In: Journal of Bone and Mineral Research. 2017.
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