Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra
Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra
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DOI：
10.1359/jbmr.2003.18.3.512
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发表时间：
2003-03-01
影响因子：
6.2
通讯作者：
Norimatsu, H
中科院分区：
文献类型：
--
作者：
Komatsubara, S;Mori, K;Norimatsu, H
本研究旨在探讨双膦酸盐长期抑制骨吸收对骨小梁的微观结构、微损伤积累和力学性能的影响。29只1岁比格犬（15只雄性，14只雌性）被分为三组。对照组（CNT）每日接受溶媒治疗，另外两组接受因卡膦酸盐治疗，剂量为0.3 mg/kg/天（低）或0.6 mg/kg/天（高），口服3年。死亡后，第二胸椎扫描与微型计算机断层扫描（micro-CT），并分配到组织形态学和微损伤测量。通过压缩对第四腰椎进行力学测试。在第11胸椎中测量骨中的因卡膦酸盐浓度。Micro-CT分析显示，因卡膦酸盐给药组胸椎中存在板状骨小梁结构和骨小梁凹面增加。3年的因卡膦酸盐治疗显著抑制了小梁激活率，LOW组为56%，HIGH组为67%，而未损害矿化，并增加了两个因卡膦酸盐治疗组的微损伤累积。与CNT组相比，LOW组和HIGH组的骨小梁体积显著增加，HIGH组的椎体强度显著增加。然而，固有的材料性能，如归一化的极限应力和归一化的韧性降低因卡膦酸盐治疗组。因卡膦酸盐在骨中的浓度呈剂量依赖性。这项研究表明，骨重建的长期抑制增加了微损伤的积累，但这并不一定与椎体脆性相关，因为骨量的补偿性增加和微结构的改善。
This study aimed to investigate the effect of long-term suppression of bone resorption by bisphosphonate on the microstructure, accumulation of microdamage, and mechanical properties of trabecular bone. Twenty-nine 1-year-old beagles (15 mates, 14 females) were divided into three groups. The control group (CNT) was treated daily with vehicle, and the other two groups were treated with incadronate at a dose of 0.3 mg/kg/day (LOW) or 0.6 mg/kg/day (HIGH) orally for 3 years. After death, the second thoracic vertebra was scanned with microcomputed tomography (micro-CT) and assigned to histomorphometric and microdamage measurements. The fourth lumbar vertebra was mechanically tested by compression. Incadronate concentration in bone was measured in the 11th thoracic vertebra. Micro-CT analysis demonstrated a platelike trabecular structure and increased concave surface of trabeculae in the thoracic vertebra of incadronate-treated groups. Three-year incadronate treatment significantly suppressed trabecular activation rates by 56% in LOW and 67% in HIGH without impairment of mineralization, and increased microdamage accumulation in both incadronate-treated groups. Trabecular bone volume was significantly increased in both LOW and HIGH groups, and vertebral strength was significantly increased in the HIGH group compared with the CNT group. However, intrinsic material properties such as normalized ultimate stress and normalized toughness were reduced in incadronate-treated groups. Incadronate concentration in bone was dose-dependent. This study suggests that long-term suppression of bone remodeling increases microdamage accumulation, but this is not necessarily associated with vertebral fragility because of compensated increase of bone mass and improved microarchitecture.