Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib.
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.
Komatsubara
Satoshi
S
Department of Orthopedic Surgery, Kagawa University, Kagawa, Japan.
Mori
Satoshi
S
Mashiba
Tasuku
T
Li
Jilliang
J
Nonaka
Kiichi
K
Kaji
Yoshio
Y
Akiyama
Tomoyuki
T
Miyamoto
Kensaku
K
Cao
Yongping
Y
Kawanishi
Jun
J
Norimatsu
Hiromichi
H
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
D004164:Diphosphonates