Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra

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Allen, M. R.¹; Gineyts, E.²; Leeming, D. J.³; Burr, D. B.^1,4,5; Delmas, P. D.²

Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra

Osteoporos Int. March 2008;19(3):329-337

©2007 International Osteoporosis Foundation and National Osteoporosis Foundation

Affiliations

¹Department of Anatomy and Cell Biology, MS 5035, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA

²INSERM Unit 403 and Université Claude Bernard Lyon1, Lyon, France

³Nordic Bioscience Diagnostics, Herlev, Denmark

⁴Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

⁵Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA
Abstract and keywords

Summary: Changes in organic matrix may contribute to the anti-fracture efficacy of anti-remodeling agents. Following one year of treatment in beagle dogs, bisphosphonates alter the organic matrix of vertebral trabecular bone, while raloxifene had no effect. These results show that pharmacological suppression of turnover alters the organic matrix component of bone.

Introduction: The collagen matrix contributes significantly to a bone’s fracture resistance yet the effects of anti-remodeling agents on collagen properties are unclear. The goal of this study was to assess changes in collagen cross-linking and isomerization following anti-remodeling treatment.

Methods: Skeletally mature female beagles were treated for one year with oral doses of vehicle (VEH), risedronate (RIS; 3 doses), alendronate (ALN; 3 doses), or raloxifene (RAL; 2 doses). The middle dose of RIS and ALN and the lower dose of RAL approximate doses used for treatment of post menopausal osteoporosis. Vertebral trabecular bone matrix was assessed for collagen isomerization (ratio of α/β C-telopeptide [CTX]), enzymatic (pyridinoline [PYD] and deoxypyridinoline [DPD]), and non-enzymatic (pentosidine [PEN]) cross-links.

Results: All doses of both RIS and ALN increased PEN (+34–58%) and the ratio of PYD/DPD (+14–26%), and decreased the ratio of α/β CTX (−29–56%) compared to VEH. RAL did not alter any collagen parameters. Bone turnover rate was significantly correlated to PEN (R=−0.664), α/β CTX (R=0.586), and PYD/DPD (R=−0.470).

Conclusions: Bisphosphonate treatment significantly alters properties of bone collagen suggesting a contribution of the organic matrix to the anti-fracture efficacy of this drug class.

Keywords: Alendronate; Anti-remodeling; Bone markers. Pentosidine; Raloxifene; Risedronate
Links

DOI: 10.1007/s00198-007-0533-7

PubMed: 18094911

WoS: 000252889400009
History

Received: 1997-05-11

Accepted: 2007-07-09

Online: 2007-12-18

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2010	Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL. Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone. March 2010;46(3):666-672.
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2013	Burket JC, Brooks DJ, MacLeay JM, Baker SP, Boskey AL, van der Meulen MCH. Variations in nanomechanical properties and tissue composition within trabeculae from an ovine model of osteoporosis and treatment. Bone. January 2013;52(1):326-336.
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