THe effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib

T. Mashiba, S. Mori, S. Komatsubara, Y. Cao, T. Manabe, H. Norimatsu, David Burr

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

We evaluated the effects of suppressed bone remodeling caused by bisphosphonate on microdamage accumulation and degree of mineralization of bone (DMB) for the dog rib in two independent studies. Study 1: 36 female beagles, 1-2 years old, were treated daily for 1 year with saline vehicle, risedronate at 0.5 mg/kg/day, or alendronate at 1.0 mg/kg/day. Study 2: 29 beagles, 1 year old, were given lactose, or incadronate at 0.3 mg/kg/day or 0.6 mg/kg/day for 3 years. In both studies, the ninth rib was harvested. Intracortical remodeling was significantly suppressed following either 1 year or 3 years of bisphosphonate treatment without impairment of primary mineralization, although the remodeling rate was obviously lower in study 2 than in study 1 because of the aging of animals. Microdamage accumulation was significantly increased following any bisphosphonate treatment in response to the extent of remodeling suppression. One-year treatment with risedronate or alendronate did not significantly affect the mean DMB or osteonal distribution based on DMB. In contrast, mean DMB was significantly increased following 3 years of incadronate treatments, and osteonal distributions based on DMB showed a dose-dependent shift toward the higher values in incadronate-treated animals when compared with controls. Our results demonstrated that DMB was increased following only 3 years but not 1 year of bisphosphonate treatment. This finding suggests that suppressed remodeling induced by long-term bisphosphonate treatment increased DMB by increasing the population of old, highly mineralized osteons; however, the expression of this phenomenon depends on duration of the treatment because the secondary mineralization is a very slow process.

Original languageEnglish
Pages (from-to)36-42
Number of pages7
JournalJournal of Bone and Mineral Metabolism
Volume23
Issue numberSUPPL. 1
DOIs
StatePublished - Jan 2005

Fingerprint

Physiologic Calcification
Bone Remodeling
Diphosphonates
Ribs
Dogs
Alendronate
Haversian System
Lactose
Cortical Bone
Population

Keywords

  • Bisphosphonate
  • Cortical bone
  • Degree of mineralization
  • Microdamage
  • Remodeling

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

THe effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. / Mashiba, T.; Mori, S.; Komatsubara, S.; Cao, Y.; Manabe, T.; Norimatsu, H.; Burr, David.

In: Journal of Bone and Mineral Metabolism, Vol. 23, No. SUPPL. 1, 01.2005, p. 36-42.

Research output: Contribution to journalArticle

Mashiba, T. ; Mori, S. ; Komatsubara, S. ; Cao, Y. ; Manabe, T. ; Norimatsu, H. ; Burr, David. / THe effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. In: Journal of Bone and Mineral Metabolism. 2005 ; Vol. 23, No. SUPPL. 1. pp. 36-42.
@article{a5eaa2271ebd4ad89cd9ff2384b8229e,
title = "THe effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib",
abstract = "We evaluated the effects of suppressed bone remodeling caused by bisphosphonate on microdamage accumulation and degree of mineralization of bone (DMB) for the dog rib in two independent studies. Study 1: 36 female beagles, 1-2 years old, were treated daily for 1 year with saline vehicle, risedronate at 0.5 mg/kg/day, or alendronate at 1.0 mg/kg/day. Study 2: 29 beagles, 1 year old, were given lactose, or incadronate at 0.3 mg/kg/day or 0.6 mg/kg/day for 3 years. In both studies, the ninth rib was harvested. Intracortical remodeling was significantly suppressed following either 1 year or 3 years of bisphosphonate treatment without impairment of primary mineralization, although the remodeling rate was obviously lower in study 2 than in study 1 because of the aging of animals. Microdamage accumulation was significantly increased following any bisphosphonate treatment in response to the extent of remodeling suppression. One-year treatment with risedronate or alendronate did not significantly affect the mean DMB or osteonal distribution based on DMB. In contrast, mean DMB was significantly increased following 3 years of incadronate treatments, and osteonal distributions based on DMB showed a dose-dependent shift toward the higher values in incadronate-treated animals when compared with controls. Our results demonstrated that DMB was increased following only 3 years but not 1 year of bisphosphonate treatment. This finding suggests that suppressed remodeling induced by long-term bisphosphonate treatment increased DMB by increasing the population of old, highly mineralized osteons; however, the expression of this phenomenon depends on duration of the treatment because the secondary mineralization is a very slow process.",
keywords = "Bisphosphonate, Cortical bone, Degree of mineralization, Microdamage, Remodeling",
author = "T. Mashiba and S. Mori and S. Komatsubara and Y. Cao and T. Manabe and H. Norimatsu and David Burr",
year = "2005",
month = "1",
doi = "10.1007/BF03026321",
language = "English",
volume = "23",
pages = "36--42",
journal = "Journal of Bone and Mineral Metabolism",
issn = "0910-0067",
publisher = "Springer Japan",
number = "SUPPL. 1",

}

TY - JOUR

T1 - THe effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib

AU - Mashiba, T.

AU - Mori, S.

AU - Komatsubara, S.

AU - Cao, Y.

AU - Manabe, T.

AU - Norimatsu, H.

AU - Burr, David

PY - 2005/1

Y1 - 2005/1

N2 - We evaluated the effects of suppressed bone remodeling caused by bisphosphonate on microdamage accumulation and degree of mineralization of bone (DMB) for the dog rib in two independent studies. Study 1: 36 female beagles, 1-2 years old, were treated daily for 1 year with saline vehicle, risedronate at 0.5 mg/kg/day, or alendronate at 1.0 mg/kg/day. Study 2: 29 beagles, 1 year old, were given lactose, or incadronate at 0.3 mg/kg/day or 0.6 mg/kg/day for 3 years. In both studies, the ninth rib was harvested. Intracortical remodeling was significantly suppressed following either 1 year or 3 years of bisphosphonate treatment without impairment of primary mineralization, although the remodeling rate was obviously lower in study 2 than in study 1 because of the aging of animals. Microdamage accumulation was significantly increased following any bisphosphonate treatment in response to the extent of remodeling suppression. One-year treatment with risedronate or alendronate did not significantly affect the mean DMB or osteonal distribution based on DMB. In contrast, mean DMB was significantly increased following 3 years of incadronate treatments, and osteonal distributions based on DMB showed a dose-dependent shift toward the higher values in incadronate-treated animals when compared with controls. Our results demonstrated that DMB was increased following only 3 years but not 1 year of bisphosphonate treatment. This finding suggests that suppressed remodeling induced by long-term bisphosphonate treatment increased DMB by increasing the population of old, highly mineralized osteons; however, the expression of this phenomenon depends on duration of the treatment because the secondary mineralization is a very slow process.

AB - We evaluated the effects of suppressed bone remodeling caused by bisphosphonate on microdamage accumulation and degree of mineralization of bone (DMB) for the dog rib in two independent studies. Study 1: 36 female beagles, 1-2 years old, were treated daily for 1 year with saline vehicle, risedronate at 0.5 mg/kg/day, or alendronate at 1.0 mg/kg/day. Study 2: 29 beagles, 1 year old, were given lactose, or incadronate at 0.3 mg/kg/day or 0.6 mg/kg/day for 3 years. In both studies, the ninth rib was harvested. Intracortical remodeling was significantly suppressed following either 1 year or 3 years of bisphosphonate treatment without impairment of primary mineralization, although the remodeling rate was obviously lower in study 2 than in study 1 because of the aging of animals. Microdamage accumulation was significantly increased following any bisphosphonate treatment in response to the extent of remodeling suppression. One-year treatment with risedronate or alendronate did not significantly affect the mean DMB or osteonal distribution based on DMB. In contrast, mean DMB was significantly increased following 3 years of incadronate treatments, and osteonal distributions based on DMB showed a dose-dependent shift toward the higher values in incadronate-treated animals when compared with controls. Our results demonstrated that DMB was increased following only 3 years but not 1 year of bisphosphonate treatment. This finding suggests that suppressed remodeling induced by long-term bisphosphonate treatment increased DMB by increasing the population of old, highly mineralized osteons; however, the expression of this phenomenon depends on duration of the treatment because the secondary mineralization is a very slow process.

KW - Bisphosphonate

KW - Cortical bone

KW - Degree of mineralization

KW - Microdamage

KW - Remodeling

UR - http://www.scopus.com/inward/record.url?scp=23844478623&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23844478623&partnerID=8YFLogxK

U2 - 10.1007/BF03026321

DO - 10.1007/BF03026321

M3 - Article

VL - 23

SP - 36

EP - 42

JO - Journal of Bone and Mineral Metabolism

JF - Journal of Bone and Mineral Metabolism

SN - 0910-0067

IS - SUPPL. 1

ER -