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Collagen maturity, glycation induced-pentosidine, and mineralization are increased following 3-year treatment with incadronate in dogs

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Abstract

Summary

Collagen cross-linking is a determinant of bone quality. A three-year treatment of bisphosphonate—incadronate disodium—in beagles increased degree of mineralization, collagen maturity, and pentosidine, a compound with advanced glycation end products. The treatment had no effect on the total amount of enzymatic cross-link formation.

Introduction

Collagen cross-linking is a determinant of bone quality. Recently, we reported that long-term treatment with bisphosphonate increased microdamage accumulation. The aim of this study was to clarify the effect of a three-year treatment with bisphosphonate on degree of mineralization and immature and mature enzymatic cross-links and non-enzymatic collagen cross-link, pentosidine, in cortical bone in the same dogs.

Methods

Twenty-nine 1-year-old beagles (15 males, 14 females) were divided into three groups that daily were given vehicle or incadronate at doses of 0.3 or 0.6 mg/kg/day orally for three years. A cortex of a rib was fractionated into low- and high-density portions. The contents of calcium, phosphorus, enzymatic immature and mature cross-links, and the non-enzymatic glycation product pentosidine were determined in each fraction.

Results

Calcium, phosphorus, and pentosidine contents and the ratio of mature to immature cross-links increased significantly with incadronate in a dose-dependent manner, but the total amount of enzymatic cross-links was unchanged. The pentosidine content correlated inversely with cortical activation frequency (p < 0.01).

Conclusion

Long-term suppression of bone remodeling by bisphosphonate increases degree of mineralization, collagen maturity, and non-enzymatic cross-linking.

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Acknowledgements

The authors are grateful to Mika Kawada, Yoshiko Fukuda, Kazumi Hirakawa for technical support and Tatsuhiko Kuroda (Tokyo Women’s Medical University) and Shiro Tanaka (Department of Epidemiology and Biostatistics, Tokyo University) for statistical analyses.

Conflicts of interest

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Jikei University School of Medicine, 3–25–8, Nishi-Shinbashi, Minato-ku, Tokyo, 105–8461, Japan

    M. Saito & K. Marumo

  2. Department of Bone and Joint Surgery, Seirei Hamamatsu General Hospital, 2-12-12, Sumiyoshi, Naka-ku, Hamamatsu, Shizuoka, 430-8558, Japan

    S. Mori

  3. Department of Orthopaedic Surgery, Kagawa University, 1750-1, Ikedo, Miki, Kida, Kagawa, 761-0793, Japan

    T. Mashiba & S. Komatsubara

Authors
  1. M. Saito
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  2. S. Mori
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  4. S. Komatsubara
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Correspondence to M. Saito.

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Saito, M., Mori, S., Mashiba, T. et al. Collagen maturity, glycation induced-pentosidine, and mineralization are increased following 3-year treatment with incadronate in dogs. Osteoporos Int 19, 1343–1354 (2008). https://doi.org/10.1007/s00198-008-0585-3

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