Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate

Matthew Allen, Ken Iwata, Roger Phipps, David Burr

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

One year of treatment with bisphosphonates at 5× the dose used for post-menopausal osteoporosis significantly increases failure load and microdamage, and decreases toughness at multiple skeletal sites in intact female beagles. The goal of this study was to determine if similar changes occur with doses equivalent to those used for post-menopausal osteoporosis treatment. Skeletally-mature female beagles were treated daily for 1 year with vehicle (VEH) or one of three doses of risedronate (RIS; 0.05, 0.10, 0.50 mg/kg/day) or alendronate (ALN; 0.10, 0.20, 1.00 mg/kg/day). Doses of ALN corresponded to treatment dose for PMO, 1/2 that dose, and 5× that dose on a mg/kg basis; RIS was given at a dose-equivalent to ALN. Vertebral density, geometry, percent ash, static/dynamic histology, microdamage, and biomechanical parameters were quantified. Trabecular bone activation frequency (Ac.f) was dose-dependently lower in RIS-treated groups (- 40%, - 66%, - 84%, P < 0.05 vs. VEH) while the three ALN groups were all similarly lower compared to VEH (- 65%, - 71%, - 76%; P < 0.05). Crack surface density (Cr.S.Dn) was significantly higher than VEH for all doses of RIS and ALN (+2.9 to 5.4-fold vs. VEH). Stiffness was significantly increased with both agents while there were no significant changes in any other structural or estimated material properties. Cr.S.Dn and Ac.f exhibited a significant non-linear correlation (r2 = 0.21; P < 0.001) while there was no relationship between Cr.S.Dn and any mechanical properties. These results document that 1 year of bisphosphonate treatment at clinical doses allows significant accumulation of microdamage in the vertebra but this is offset by increases in bone volume and mineralization such that there is no significant impairment of mechanical properties.

Original languageEnglish
Pages (from-to)872-879
Number of pages8
JournalBone
Volume39
Issue number4
DOIs
StatePublished - Oct 2006

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Alendronate
Bone Remodeling
Canidae
Postmenopausal Osteoporosis
Diphosphonates
Physiologic Calcification
Therapeutics
Histology
Spine
Risedronate Sodium

Keywords

  • Bisphosphonate
  • Histomorphometry
  • Osteoporosis
  • Remodeling

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. / Allen, Matthew; Iwata, Ken; Phipps, Roger; Burr, David.

In: Bone, Vol. 39, No. 4, 10.2006, p. 872-879.

Research output: Contribution to journalArticle

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title = "Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate",
abstract = "One year of treatment with bisphosphonates at 5× the dose used for post-menopausal osteoporosis significantly increases failure load and microdamage, and decreases toughness at multiple skeletal sites in intact female beagles. The goal of this study was to determine if similar changes occur with doses equivalent to those used for post-menopausal osteoporosis treatment. Skeletally-mature female beagles were treated daily for 1 year with vehicle (VEH) or one of three doses of risedronate (RIS; 0.05, 0.10, 0.50 mg/kg/day) or alendronate (ALN; 0.10, 0.20, 1.00 mg/kg/day). Doses of ALN corresponded to treatment dose for PMO, 1/2 that dose, and 5× that dose on a mg/kg basis; RIS was given at a dose-equivalent to ALN. Vertebral density, geometry, percent ash, static/dynamic histology, microdamage, and biomechanical parameters were quantified. Trabecular bone activation frequency (Ac.f) was dose-dependently lower in RIS-treated groups (- 40{\%}, - 66{\%}, - 84{\%}, P < 0.05 vs. VEH) while the three ALN groups were all similarly lower compared to VEH (- 65{\%}, - 71{\%}, - 76{\%}; P < 0.05). Crack surface density (Cr.S.Dn) was significantly higher than VEH for all doses of RIS and ALN (+2.9 to 5.4-fold vs. VEH). Stiffness was significantly increased with both agents while there were no significant changes in any other structural or estimated material properties. Cr.S.Dn and Ac.f exhibited a significant non-linear correlation (r2 = 0.21; P < 0.001) while there was no relationship between Cr.S.Dn and any mechanical properties. These results document that 1 year of bisphosphonate treatment at clinical doses allows significant accumulation of microdamage in the vertebra but this is offset by increases in bone volume and mineralization such that there is no significant impairment of mechanical properties.",
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N2 - One year of treatment with bisphosphonates at 5× the dose used for post-menopausal osteoporosis significantly increases failure load and microdamage, and decreases toughness at multiple skeletal sites in intact female beagles. The goal of this study was to determine if similar changes occur with doses equivalent to those used for post-menopausal osteoporosis treatment. Skeletally-mature female beagles were treated daily for 1 year with vehicle (VEH) or one of three doses of risedronate (RIS; 0.05, 0.10, 0.50 mg/kg/day) or alendronate (ALN; 0.10, 0.20, 1.00 mg/kg/day). Doses of ALN corresponded to treatment dose for PMO, 1/2 that dose, and 5× that dose on a mg/kg basis; RIS was given at a dose-equivalent to ALN. Vertebral density, geometry, percent ash, static/dynamic histology, microdamage, and biomechanical parameters were quantified. Trabecular bone activation frequency (Ac.f) was dose-dependently lower in RIS-treated groups (- 40%, - 66%, - 84%, P < 0.05 vs. VEH) while the three ALN groups were all similarly lower compared to VEH (- 65%, - 71%, - 76%; P < 0.05). Crack surface density (Cr.S.Dn) was significantly higher than VEH for all doses of RIS and ALN (+2.9 to 5.4-fold vs. VEH). Stiffness was significantly increased with both agents while there were no significant changes in any other structural or estimated material properties. Cr.S.Dn and Ac.f exhibited a significant non-linear correlation (r2 = 0.21; P < 0.001) while there was no relationship between Cr.S.Dn and any mechanical properties. These results document that 1 year of bisphosphonate treatment at clinical doses allows significant accumulation of microdamage in the vertebra but this is offset by increases in bone volume and mineralization such that there is no significant impairment of mechanical properties.

AB - One year of treatment with bisphosphonates at 5× the dose used for post-menopausal osteoporosis significantly increases failure load and microdamage, and decreases toughness at multiple skeletal sites in intact female beagles. The goal of this study was to determine if similar changes occur with doses equivalent to those used for post-menopausal osteoporosis treatment. Skeletally-mature female beagles were treated daily for 1 year with vehicle (VEH) or one of three doses of risedronate (RIS; 0.05, 0.10, 0.50 mg/kg/day) or alendronate (ALN; 0.10, 0.20, 1.00 mg/kg/day). Doses of ALN corresponded to treatment dose for PMO, 1/2 that dose, and 5× that dose on a mg/kg basis; RIS was given at a dose-equivalent to ALN. Vertebral density, geometry, percent ash, static/dynamic histology, microdamage, and biomechanical parameters were quantified. Trabecular bone activation frequency (Ac.f) was dose-dependently lower in RIS-treated groups (- 40%, - 66%, - 84%, P < 0.05 vs. VEH) while the three ALN groups were all similarly lower compared to VEH (- 65%, - 71%, - 76%; P < 0.05). Crack surface density (Cr.S.Dn) was significantly higher than VEH for all doses of RIS and ALN (+2.9 to 5.4-fold vs. VEH). Stiffness was significantly increased with both agents while there were no significant changes in any other structural or estimated material properties. Cr.S.Dn and Ac.f exhibited a significant non-linear correlation (r2 = 0.21; P < 0.001) while there was no relationship between Cr.S.Dn and any mechanical properties. These results document that 1 year of bisphosphonate treatment at clinical doses allows significant accumulation of microdamage in the vertebra but this is offset by increases in bone volume and mineralization such that there is no significant impairment of mechanical properties.

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