Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles
Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles
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DOI：
10.1016/s8756-3282(01)00414-8
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发表时间：
2001-05-01
期刊：
影响因子：
4.1
通讯作者：
Burr, DB
中科院分区：
文献类型：
--
作者：
Mashiba, T;Turner, CH;Burr, DB
我们最近证明，抑制骨重建允许微损伤积累，导致狗肋骨皮质骨韧性降低。本研究评价了双膦酸盐引起的骨转换减少对相同犬临床相关骨骼部位微损伤累积和生物力学特性的影响。将36只1-2岁雌性比格犬分为3组。对照组每日口服生理盐水（CNT），其余两组每日口服利塞膦酸钠0.5mg/kg/d（RIS）或阿仑膦酸钠1.0mg/kg/d（ALN）。处死后行双能X线骨密度仪（DXA）扫描L1椎体，L2椎体和右侧髂骨进行组织形态计量学分析，L3椎体、左侧髂骨、Th-2棘突和右侧股骨颈进行显微损伤分析。分别对L-4椎骨和Th-1棘突进行压缩和剪切力学试验。利塞膦酸钠或阿仑膦酸钠治疗一年可显着抑制椎骨（RIS 90%，ALN 95%）和髂骨（RIS 76%，ALN 90%）的小梁重塑，而不损害矿化，并显着增加所有测量骨骼部位的微损伤累积。治疗12个月后，松质骨体积和椎体强度显著增加。然而，RIS（p = 0.06）和ALN（p = 0.05）组的L-4椎骨的标准化韧性均降低了21%。当两个双膦酸盐组以事后方式合并进行分析时，韧性的降低达到统计学显著性（p = 0.02）。该研究表明，高剂量双膦酸盐对骨小梁转换的抑制与椎骨强度增加相关，即使存在显著的微损伤累积和骨小梁内在能量吸收能力的降低。(C)2001年，Elsevier Science Inc. All rights reserved.
We recently demonstrated that suppression of bone remodeling allows microdamage to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This study evaluates the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties at clinically relevant skeletal sites in the same dogs. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle (CNT), The remaining two groups were treated daily with risedronate at a dose of 0.5 mg/kg per day (RIS), or alendronate at 1.0 mg/kg per day (ALN) orally, The doses of these bisphosphonates were six times the clinical doses approved for treatment of osteoporosis in humans. After killing, the L-1 vertebra was scanned by dual-energy X-ray absorptiometry (DXA), and the L-2 vertebra and right ilium were assigned to histomorphometry, The L-3 vertebra, left ilium, Th-2 spinous process, and right femoral neck were used for microdamage analysis. The L-4 vertebra and Th-1 spinous process were mechanically tested to failure in compression and shear, respectively. One year treatment with risedronate or alendronate significantly suppressed trabecular remodeling in vertebrae (RIS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of mineralization, and significantly increased microdamage accumulation in all skeletal sites measured. Trabecular bone volume and vertebral strength increased significantly following 12 month treatment. However, normalized toughness of the L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0.05) groups. When the two bisphosphonate groups were pooled in a post hoc fashion for analysis, this reduction in toughness reached statistical significance (p = 0.02), This study demonstrates that suppression of trabecular bone turnover by high doses of bisphosphonates is associated with increased vertebral strength, even though there is significant microdamage accumulation and a reduction in the intrinsic energy absorption capacity of trabecular bone. (C) 2001 by Elsevier Science Inc. All rights reserved.