title: Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib.
abstract: Effects of long-term suppression of bone remodeling by bisphosphonate were investigated in cortical bone of dog rib. Although microdamage was accumulated, BMD was increased without increasing cortical bone area. Consequently, the intrinsic material properties were not reduced.
  
  
  BACKGROUND
  Recently, we have reported that long-term suppression of bone remodeling increases microdamage accumulation but is not necessarily associated with vertebral fragility because of compensated increase of bone mass and improved microarchitecture. This study aimed to investigate the effect of long-term suppression of bone remodeling by bisphosphonate on the degree of mineralization, accumulation of microdamage, and mechanical properties of cortical bone in the same dogs.
  
  
  METHODS
  Twenty-nine 1-year-old beagles (15 males, 14 females) were divided into three groups and treated daily with vehicle (CNT) or with incadronate at a dose of 0.3 (LOW) or 0.6 mg/kg/day (HIGH) orally for 3 years. After death, pQCT, histomorphometry, microdamage measurements, and three-point bending mechanical test were performed using the ninth rib.
  
  
  RESULTS
  Cortical BMD was increased in the incadronate-treated groups. Cortical activation frequency was suppressed by 82% and 70% in HIGH and LOW, respectively, compared with CNT, without impairment of mineralization. Microdamage accumulation was increased in both incadronate-treated groups. Although there were no significant differences in total and cortical area among the three groups, structural mechanical properties were significantly increased after incadronate treatment while intrinsic material properties were not changed in the incadronate-treated groups.
  
  
  CONCLUSIONS
  This study suggests that long-term suppression of bone remodeling by bisphosphonate increases microdamage accumulation. However, this was not necessarily associated with a reduction of intrinsic material properties probably because of an increased degree of mineralization.
authors.affiliation: Department of Orthopedic Surgery, Kagawa University, Kagawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Komatsubara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mori
authors.forename: Tasuku
authors.initials: T
authors.lastname: Mashiba
authors.forename: Jilliang
authors.initials: J
authors.lastname: Li
authors.forename: Kiichi
authors.initials: K
authors.lastname: Nonaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kaji
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akiyama
authors.forename: Kensaku
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cao
authors.forename: Jun
authors.initials: J
authors.lastname: Kawanishi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Norimatsu
mesh_terms: D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D008297:Male; D012272:Ribs / Q000187:drug effects* / Q000473:pathology
chemical_list: D004164:Diphosphonates