Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate

S. Y. Tang, Matthew Allen, R. Phipps, David Burr, D. Vashishth

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Summary: One year of high-dose bisphosphonate (BPs) therapy in dogs allowed the increased accumulation of advanced glycation end-products (AGEs) and reduced postyield work-to-fracture of the cortical bone matrix. The increased accumulation of AGEs in these tissues may help explain altered bone matrix quality due to the administration of BPs in animal models Introduction: Non-enzymatic glycation (NEG) is a posttranslational modification of the organic matrix that results in the formation of advanced glycation end-products (AGEs). In bone, the accumulation of AGEs play an important role in determining fracture resistance, and elevated levels of AGEs have been shown to adversely affect the bone's propensity to brittle fracture. It was thus hypothesized that the suppression of tissue turnover in cortical bone due to the administration of bisphosphonates would cause increased accumulation of AGEs and result in a more brittle bone matrix. Methods: Using a canine animal model (n∈=∈12), we administered daily doses of a saline vehicle (VEH), alendronate (ALN 0.20, 1.00 mg/kg) or risedronate (RIS 0.10, 0.50 mg/kg). After a 1-year treatment, the mechanical properties, intracortical bone turnover, and the degree of nonenzymatic cross-linking of the organic matrix were measured from the tibial cortical bone tissue of these animals. Results: There was a significant accumulation of AGEs at high treatment doses (+49 to + 86%; p∈<∈0. 001), but not at doses equivalent to those used for the treatment of postmenopausal osteoporosis, compared to vehicle. Likewise, postyield work-to-fracture of the tissue was significantly reduced at these high doses (-28% to -51%; p∈<∈0.001) compared to VEH. AGE accumulation inversely correlated with postyield work-to-fracture (r 2∈= ∈0.45; p∈<∈0.001), suggesting that increased AGEs may contribute to a more brittle bone matrix. Conclusion: High doses of bisphosphonates result in the accumulation of AGEs and a reduction in energy absorption of cortical bone. The increased accumulation of AGEs in these tissues may help explain altered bone matrix quality due to the administration of BPs in animal models.

Original languageEnglish
Pages (from-to)887-894
Number of pages8
JournalOsteoporosis International
Volume20
Issue number6
DOIs
StatePublished - Jun 2009

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Alendronate
Advanced Glycosylation End Products
Bone Matrix
Diphosphonates
Animal Models
Bone and Bones
Risedronate Sodium
Postmenopausal Osteoporosis
Bone Remodeling
Post Translational Protein Processing
Canidae

Keywords

  • Advanced glycation end-products
  • Alendronate
  • Animal models
  • Bisphosphonates
  • Non-enzymatic glycation
  • Osteoporosis
  • Risedronate

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. / Tang, S. Y.; Allen, Matthew; Phipps, R.; Burr, David; Vashishth, D.

In: Osteoporosis International, Vol. 20, No. 6, 06.2009, p. 887-894.

Research output: Contribution to journalArticle

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AU - Burr, David

AU - Vashishth, D.

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N2 - Summary: One year of high-dose bisphosphonate (BPs) therapy in dogs allowed the increased accumulation of advanced glycation end-products (AGEs) and reduced postyield work-to-fracture of the cortical bone matrix. The increased accumulation of AGEs in these tissues may help explain altered bone matrix quality due to the administration of BPs in animal models Introduction: Non-enzymatic glycation (NEG) is a posttranslational modification of the organic matrix that results in the formation of advanced glycation end-products (AGEs). In bone, the accumulation of AGEs play an important role in determining fracture resistance, and elevated levels of AGEs have been shown to adversely affect the bone's propensity to brittle fracture. It was thus hypothesized that the suppression of tissue turnover in cortical bone due to the administration of bisphosphonates would cause increased accumulation of AGEs and result in a more brittle bone matrix. Methods: Using a canine animal model (n∈=∈12), we administered daily doses of a saline vehicle (VEH), alendronate (ALN 0.20, 1.00 mg/kg) or risedronate (RIS 0.10, 0.50 mg/kg). After a 1-year treatment, the mechanical properties, intracortical bone turnover, and the degree of nonenzymatic cross-linking of the organic matrix were measured from the tibial cortical bone tissue of these animals. Results: There was a significant accumulation of AGEs at high treatment doses (+49 to + 86%; p∈<∈0. 001), but not at doses equivalent to those used for the treatment of postmenopausal osteoporosis, compared to vehicle. Likewise, postyield work-to-fracture of the tissue was significantly reduced at these high doses (-28% to -51%; p∈<∈0.001) compared to VEH. AGE accumulation inversely correlated with postyield work-to-fracture (r 2∈= ∈0.45; p∈<∈0.001), suggesting that increased AGEs may contribute to a more brittle bone matrix. Conclusion: High doses of bisphosphonates result in the accumulation of AGEs and a reduction in energy absorption of cortical bone. The increased accumulation of AGEs in these tissues may help explain altered bone matrix quality due to the administration of BPs in animal models.

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