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

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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.

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