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Five Years of Treatment with Risedronate and its Effects on Bone Safety in Women with Postmenopausal Osteoporosis

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Abstract

We have recently reported that risedronate preserves normal bone formation and decreases bone remodeling in women with postmenopausal osteoporosis after 3 years of treatment. We report now the results of a 2-year extension study. The primary objective of this study was to determine the effect of 5 years of risedronate treatment (5 mg daily) on bone quality and bone remodeling based on paired transiliac bone biopsies. There were additional measurements that included bone turnover markers and bone mineral density (BMD). Histologic evaluation of biopsy sections (placebo, n = 21; risedronate, n = 27) yielded no pathologic findings after 5 years in either treatment group. Histomorphometric assessment of paired biopsy specimens after 5 years (placebo, n =12; risedronate, n = 13) found no statistically significant differences between treatment groups in structural or resorption parameters. There was a significant reduction in osteoid (−27%) and mineralizing surfaces (−49%) from baseline values in the risedronate group that were also significantly different from placebo at 5 years. Similarly, activation frequency decreased significantly (−77%) in the risedronate group, although it was not significantly different from placebo at 5 years (0.09 vs. 0.21, respectively). Double tetracycline labels were identified in all biopsy specimens indicating continuous bone turnover. After 5 years of risedronate treatment, serum bone-specific alkaline phosphatase (bone ALP) and N-telopeptide (NTX) decreased significantly from baseline by 33.3% and 47.5%, respectively. In the placebo group, bone ALP decreased by 3.9% (P = NS), whereas NTX decreased by 27.0% (P < 0.005). Lumbar spine BMD increased significantly in the risedronate group (9.2%), whereas no significant change was seen in the placebo group (−0.26%). Risedronate was overall well tolerated; during the 2-year study extension nonvertebral fractures occurred in 7 patients in placebo and 2 patients in risedronate groups. The findings from this study are consistent with the antiremodeling effect of risedronate and support long-term bone safety and antifracture efficacy of risedronate treatment.

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Acknowledgments

We are grateful to Elaine B. Taylor for her assistance in the preparation and editing of the manuscript. We thank Dr. Erik Eriksen for histomorphometric analysis of the bone biopsies and Dr. Flemming Melsen for histopathologic assessments of the biopsy specimens.

The following investigators obtained patient biopsy specimens for this study: E. Boling, Rancho Cucamonga, California; J. Brown, Sainte-Foy, Quebec, Canada; R. Emkey, Reading, Pennsylvania; M. Ettinger, Stuart, Florida; M. Greenwald, Palm Springs, California; D. Hanley, Calgary, Alberta, Canada; A. Hodsman, London, Ontario, Canada; M. Keller, San Diego, California; R. Khairi, Indianapolis, Indiana; A. Licata, Cleveland, Ohio; C. McKeever, Houston, Texas; P. Miller, Lakewood, Colorado; L. Ste-Marie, Montreal, Quebec, Canada; and N. Watts, Cincinnati, Ohio.

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Authors and Affiliations

  1. Centre de Recherche du CHUM Hôspital, Saint-Luc Montreal, Quebec, Canada

    L.-G. Ste-Marie

  2. Procter & Gamble Pharmaceuticals, Inc., Mason, Ohio, USA

    E. Sod, T. Johnson & A. Chines

Authors
  1. L.-G. Ste-Marie
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  2. E. Sod
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  3. T. Johnson
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  4. A. Chines
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Corresponding author

Correspondence to A. Chines.

Additional information

This work was supported by grants from Procter & Gamble Pharmaceuticals, Inc., Mason, Ohio, and Aventis Pharmaceuticals, Bridgewater, New Jersey.

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Ste-Marie, LG., Sod, E., Johnson, T. et al. Five Years of Treatment with Risedronate and its Effects on Bone Safety in Women with Postmenopausal Osteoporosis. Calcif Tissue Int 75, 469–476 (2004). https://doi.org/10.1007/s00223-004-0039-7

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