Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients

Authors

  • A. Deodhar,

    Corresponding author
    1. Oregon Health & Science University, Portland
    • Division of Arthritis and Rheumatic Diseases (OP09), Oregon Health & Science University, Portland, OR 97239
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    • Dr. Deodhar has received consultancies and speaking fees (less than $10,000 each) from Centocor, Genentech, and Takeda.

  • R. K. Dore,

    1. Robin K. Dore, MD, Inc., Tustin, California
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    • Dr. Dore has received consultant fees, speaking fees, and honoraria (more than $10,000) from Amgen Inc.

  • D. Mandel,

    1. Private Practice, Mayfield Village, Ohio
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    • Dr. Mandel has received speaking fees (less than $10,000 each) from Amgen, GlaxoSmithKline, and Novartis.

  • J. Schechtman,

    1. Sun Valley Arthritis Center, Ltd., Peoria, Arizona
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    • Dr. Schechtman has received consultant fees, speaking fees, and/or honoraria (more than $10,000 each) and/or has served on the advisory boards for Amgen, Bristol-Myers Squibb, CanFite, Centacore, Eli Lilly, Genentech, GlaxoSmithKline, Pfizer, Primus, Roche, Tap, Targeted Genetics, Abbott, Design Write, Encysive, Genie/Scienomics Group, Merck, PriCare/Ortho-McNeill, and Wyeth.

  • W. Shergy,

    1. Rheumatology Associates of North Alabama, Huntsville
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  • R. Trapp,

    1. The Arthritis Center, Springfield, Illinois
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    • Dr. Trapp owns stock and/or holds stock options in Amgen Inc.

  • P. A. Ory,

    1. Highline Medical Center, University of Washington, Seattle
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    • Dr. Ory has received consultant fees (less than $10,000) from Amgen Inc.

  • C. G. Peterfy,

    1. Synarc Inc., San Francisco, California
    Current affiliation:
    1. Spire Sciences LLC, San Francisco, California
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    • Dr. Peterfy owns stock and/or holds stock options in Spire Sciences LLC and Synarc Inc.

  • T. Fuerst,

    1. Synarc Inc., San Francisco, California
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    • Dr. Fuerst owns stock and/or holds stock options in Synarc Inc.

  • H. Wang,

    1. Amgen Inc., Thousand Oaks, California
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    • Drs. Wang, Zhou, Tsuji, and Newmark own stock and/or hold stock options in Amgen Inc.

  • L. Zhou,

    1. Amgen Inc., Thousand Oaks, California
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    • Drs. Wang, Zhou, Tsuji, and Newmark own stock and/or hold stock options in Amgen Inc.

  • W. Tsuji,

    1. Amgen Inc., Seattle, Washington
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    • Drs. Wang, Zhou, Tsuji, and Newmark own stock and/or hold stock options in Amgen Inc.

  • R. Newmark

    1. Amgen Inc., Thousand Oaks, California
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    • Drs. Wang, Zhou, Tsuji, and Newmark own stock and/or hold stock options in Amgen Inc.


Abstract

Objective

Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores.

Methods

Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months).

Results

There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and −1.2% and −2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores.

Conclusion

In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.

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