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Fracture risk remains reduced one year after discontinuation of risedronate

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Abstract

Summary

One year after discontinuation of three year’s treatment with risedronate, BMD decreased at the lumbar spine and femoral neck and bone turnover markers returned to control group levels. Despite these changes, the risk of new morphometric vertebral fractures remained lower in previous risedronate patients compared with previous control patients.

Introduction

Differences in bisphosphonate pharmacology and pharmacokinetics could influence persistence or resolution of the effects once treatment is stopped. We investigated changes in intermediate markers—bone mineral density (BMD) and bone turnover markers (BTM)—and fracture risk after discontinuation of treatment with risedronate.

Methods

Patients who received risedronate 5 mg daily (N = 398) or placebo (N = 361) during the VERT-NA study stopped therapy per protocol after 3 years but continued taking vitamin D (if levels at study entry were low) and calcium and were reassessed one year later.

Results

In the year off treatment, spine BMD decreased significantly, but remained higher than baseline (p ≤ 0.001) and placebo (p < 0.001), with similar findings at the femoral neck and trochanter. Urinary NTX and bone-specific alkaline phosphatase, which decreased significantly with treatment, were not significantly different from placebo after 1 year off treatment. Despite the changes in intermediate markers, the incidence of new morphometric vertebral fractures was 46% lower in the former risedronate group compared with the former placebo group (RR 0.54 [95% CI, 0.34, 0.86, p = 0.009]).

Conclusions

Despite the apparent resolution of effect on BMD and BTM, the risk reduction of new vertebral fractures remained in the year after treatment with risedronate was stopped.

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Acknowledgments

We would like to acknowledge Rosemary Hannon, Ph.D. for performing the NTX measurements reported in this study, Ruby Xia and John Banner, M.S. for performing part of the statistical analyses reported in this study as well as all the investigators and staff at the study centers.

Conflict of interest statements

Dr. Watts receives honoraria for lectures from Amgen, Novartis, Procter & Gamble and sanofi-aventis; consulting fees from Amgen, Eli Lilly, Kyphon, Novartis, Procter & Gamble, Roche and sanofi-aventis; and research support through Amgen, Eli Lilly, Novartis, Procter & Gamble and Solvay.

Dr. Chines is a former employee of Procter & Gamble and owns Procter & Gamble shares. He is currently an employee of Wyeth.

Dr. McKeever is a consultant for Procter & Gamble, Merck and Roche and receives research grants from Procter & Gamble, Merck, Lilly and Roche.

Dr. McClung receives research grants from Amgen, Eli Lilly, Merck, Novartis, Procter & Gamble, and Roche. He receives consulting fees from Amgen, Eli Lilly, Merck, Novartis, Procter & Gamble, Roche and sanofi-aventis. He is a member of speaker’s bureaus for Eli Lilly, Merck, Procter & Gamble, and sanofi-aventis.

Dr. Zhou and Dr. Grauer are full time employees of Procter & Gamble and own stocks of the company.

Author information

Authors and Affiliations

  1. University of Cincinnati Bone Health and Osteoporosis Center, 222 Piedmont Avenue, Suite 4300, Cincinnati, OH, 45219, USA

    N. B. Watts

  2. Procter & Gamble Pharmaceuticals, Cincinnati, OH, USA

    A. Chines, X. Zhou & A. Grauer

  3. Midtown Medical Center, Saskatoon, SK, Canada

    W. P. Olszynski

  4. McKeever Orthopedic Clinic, Houston, TX, USA

    C. D. McKeever

  5. Oregon Osteoporosis Center, Portland, OR, USA

    M. R. McClung

Authors
  1. N. B. Watts
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  2. A. Chines
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  3. W. P. Olszynski
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  4. C. D. McKeever
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  5. M. R. McClung
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  6. X. Zhou
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  7. A. Grauer
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Corresponding author

Correspondence to N. B. Watts.

Additional information

This study was funded by grants from Procter & Gamble Pharmaceuticals, Cincinnati, Ohio, and sanofi- aventis Pharma, Bridgewater, New Jersey.

Appendix

Appendix

Other members of the VERT-NA extension study group were: M. B. Block, Phoenix, AZ, USA; R. S. Bockman, New York, NY, USA; E. Boling, Rancho Cucamonga, CA, USA; M. Bolognese, Gaithersberg, MD, USA; S. L. Bonnick, Denton, TX, USA; S. Bowman, Clearwater, FL USA; W. Briney, Denver, CO,, USA; J. Brown, Quebec, Canada; S. Broy, Chicago, IL, USA; J. Cabral, Ft. Lauderdale, FL, USA; R. B. Cannon, Salt Lake City, UT, USA; C. Chesnut, Seattle, WA, USA; Y. D. Coble, Jacksonville, FL, USA; S. A. Cohen, Trumball, CT, USA; S. Cohen, Dallas, TX, USA; M. Davis, Mobile, AL, USA; W. Delaney, Danbury, CT, USA; G. B. Dewees, Birmingham, AL, USA; M. Doyle, Ferndale, MI, USA; R. D. Emkey, Reading, PA, USA; S. C. English, Billings, MT, USA; M. P. Ettinger, Stuart, FL, USA; , N. R. Farris, Lexington, KY,, USA; D. Freeman, Raleigh, NC, USA; N. M. Friedman, Albuquerque, NM, USA; A. B. Galway, St. Johns, Newfoundland, Canada; M. L. S. Gass, Cincinnati, OH, USA; H. Geisberg, Anderson, SC, USA; G. Gerety, Albany, NY, USA; M. Gittelman, Aventura, FL, USA; M. Greenwald, Palm Springs, CA, USA; R. C. Hamdy, Mountain Home, TN, USA; T. N. Hangartner, Dayton, OH, USA; D. A. Hanley, Calgary, Alberta, Canada; T. Harrington, Madison, WI, USA; S. T. Harris, San Francisco, CA, USA; D. J. Helfrich, Pittsburgh, PA, USA; M. Heller, Peabody, MA, USA; M. Heur, Gainesville, FL, USA; M. C. Hochberg, Baltimore, MD, USA; A. Hodsman, London, Ontario, Canada; R. D. Jackson, Columbus, OH, USA; A. J. Jacobs, Lincoln, NE, USA; P. Jellinger, Hollywood, FL, USA; C. C. Johnston, Jr., Indianapolis, IN, USA; R. Josse, Toronto, Ontario, Canada; A. V. Jovaisas, Ottawa, Ontario, Canada; J. L. Juozevicius, Kalamazoo, MI, USA; R. A. Kaplan, Concord, CA, USA; M. Keller, San Diego, CA, USA; D. L. Kendler, Vancouver, British Columbia, Canada; R. Khairi, Indianapolis, IN, USA; M. S. Kipines, San Antonio, TX, USA; A. J. Kivitz, Altoona, PA, USA; J. Kotler, Ft. Lauderdale, FL, USA; N. Koval, Wheaton, MD, USA;N. J. Kramer, Charlotte, NC, USA; A. J. Laster, Charlotte, NC, USA; E. Leib, Burlington, VT, USA; R. M. Levy, Olympia, WA, USA; A. A. Licata, Cleveland, OH, USA; R. Lies, Wichita, KS, USA; T. Littlejohn, Winston-Salem, NC, USA; M. Lowenstein, Palm Harbor, FL, USA; F. Maggiacomo, Providence, RI, USA; A. Mangione, Jenkintown, PA, USA; R. E. Marcus, Teaneck, NJ, USA; M. Maricic, Tucson, AZ, USA; M. R. McClung, Portland, OR, USA; H. H. Mcllwain, Tampa, FL, USA; P. Miller, Lakewood, CO, USA; S. S. Miller, San Antonia, TX, USA; A. Mulloy, Augusta, GA, USA; J. A. Napier, Jr., St. Petersburg, FL, USA; L. Olansky, Oklahoma City, OK, USA; S. A. Pasquale, New Brunswick, NJ, USA; D. A. Podlecki, Longmont, CO, USA; J. J. Prendergast, Atherton, CA, USA; H. M. Prupas, Reno, NV, USA; S. Quandt, Winston-Salem, NC, USA; R. J. Rapoport, Fall River, MA, T. Rooney, Des Moines, IA, USA; C. Rosen, Bangor, ME, USA; S. Rosenblatt, Irvine, CA, USA; B. Samuels, Dover, NH, USA; E. N. Schwartz, Oakland, CA, USA; S. Scumpia, Austin, TX, USA; W. J. Shergy, Huntsville, AL, USA; S. L. Silverman, Beverly Hills, CA, USA; C. L. Smith, Minneapolis, MN, USA; L. G. Ste-Marie, Montreal, Quebec, Canada; J. L. Stock, Worcester, MA, USA; A. Tenenhouse, Montreal, Quebec, Canada; A. Virshup, West Palm Beach, FL, USA; R. D. Wasnick, Honolulu, HI, USA; N. Wei, Frederick, MD, USA; S. R. Weiss, San Diego, CA, USA; T. M. Zizic, Baltimore, MD USA

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Watts, N.B., Chines, A., Olszynski, W.P. et al. Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int 19, 365–372 (2008). https://doi.org/10.1007/s00198-007-0460-7

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