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

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Saito, M.¹; Mori, S.²; Mashiba, T.³; Komatsubara, S.⁴; Marumo, K.¹

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

Osteoporos Int. September 2008;19(9):1343-1354

©2008 International Osteoporosis Foundation and National Osteoporosis Foundation

Affiliations

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

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

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

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.

Keywords: Advanced glycation end products; Bisphosphonate; Collagen cross-links; Mineralization; Non-enzymatic glycation; Pentosidine
Links

DOI: 10.1007/s00198-008-0585-3

PubMed: 18373056

WoS: 000258401200016
History

Received: 2007-09-29

Accepted: 2007-12-12

Online: 2008-03-29

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