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

Matthew Allen, E. Gineyts, D. J. Leeming, David Burr, P. D. Delmas

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)329-337
Number of pages9
JournalOsteoporosis International
Volume19
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Diphosphonates
Spine
Collagen
Dogs
Bone Matrix
Alendronate
Postmenopausal Osteoporosis
Bone Remodeling
Bone Fractures
Cancellous Bone
Pharmacology
Bone and Bones
Pharmaceutical Preparations
deoxypyridinoline
pyridinoline
pentosidine

Keywords

  • Alendronate
  • Anti-remodeling
  • Bone markers
  • Pentosidine
  • Raloxifene
  • Risedronate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra. / Allen, Matthew; Gineyts, E.; Leeming, D. J.; Burr, David; Delmas, P. D.

In: Osteoporosis International, Vol. 19, No. 3, 03.2008, p. 329-337.

Research output: Contribution to journalArticle

Allen, Matthew ; Gineyts, E. ; Leeming, D. J. ; Burr, David ; Delmas, P. D. / Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra. In: Osteoporosis International. 2008 ; Vol. 19, No. 3. pp. 329-337.
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abstract = "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.",
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