Osteoporosis International

, Volume 19, Issue 3, pp 329–337

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

  • M. R. Allen
  • E. Gineyts
  • D. J. Leeming
  • D. B. Burr
  • P. D. Delmas
Original Article

DOI: 10.1007/s00198-007-0533-7

Cite this article as:
Allen, M.R., Gineyts, E., Leeming, D.J. et al. Osteoporos Int (2008) 19: 329. doi:10.1007/s00198-007-0533-7



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.


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.


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.


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).


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


Alendronate Anti-remodeling Bone markers Pentosidine Raloxifene Risedronate 

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • M. R. Allen
    • 1
  • E. Gineyts
    • 4
  • D. J. Leeming
    • 5
  • D. B. Burr
    • 1
    • 2
    • 3
  • P. D. Delmas
    • 4
  1. 1.Department of Anatomy and Cell Biology, MS 5035Indiana University School of MedicineIndianapolisUSA
  2. 2.Department of Orthopaedic SurgeryIndiana University School of MedicineIndianapolisUSA
  3. 3.Department of Biomedical EngineeringIndiana University-Purdue University at IndianapolisIndianapolisUSA
  4. 4.INSERM Unit 403 and Université Claude Bernard Lyon1LyonFrance
  5. 5.Nordic Bioscience DiagnosticsHerlevDenmark

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