T. Mashiba et al., Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib, J BONE MIN, 15(4), 2000, pp. 613-620
It has been hypothesized that suppression of bone remodeling allows microda
mage to accumulate, leading to increased bone fragility. This study evaluat
ed the effects of reduced bone turnover produced by bisphosphonates on micr
odamage accumulation and biomechanical properties of cortical bone in the d
og rib. Thirty-six female beagles, 1-2 years old, were divided into three g
roups. The control group (CNT) was treated daily for 12 months with saline
vehicle. The remaining two groups were treated daily with risedronate (RIS)
at a dose of 0.5 mg/kg per day or alendronate (ALN) at 1.0 mg/kg per day o
rally. After sacrifice, the right ninth rib was assigned to cortical histom
orphometry or microdamage analysis. The left ninth rib was tested to failur
e in three-point bending. Total cross-sectional bone area was significantly
increased in both RIS and ALN compared with CNT, whereas cortical area did
not differ significantly among groups. One-year treatment with RIS or ALN
significantly suppressed intracortical remodeling (RIS, 53%; ALN, 68%) with
out impairment of mineralization and significantly increased microdamage ac
cumulation in both RIS (155%) and ALN (322%) compared with CNT, Although bo
ne strength and stiffness were not significantly affected by the treatments
, bone toughness declined significantly in ALN (20%), Regression analysis s
howed a significant nonlinear relationship between suppressed intracortical
bone remodeling and microdamage accumulation as well as a significant line
ar relationship between microdamage accumulation and reduced toughness. Thi
s study showed that suppression of bone turnover by high doses of bisphosph
onates is associated with microdamage accumulation and reduced some mechani
cal properties of bone.