Site specific effects of zoledronic acid during tibial and mandibular fracture repair.
Site specific effects of zoledronic acid during tibial and mandibular fracture repair.
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DOI：
10.1371/journal.pone.0031771
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Colnot C
中科院分区：
文献类型：
--
作者：
Yu YY;Lieu S;Hu D;Miclau T;Colnot C
许多因素可以影响骨骼再生，包括骨损伤的程度、机械负荷、炎症和外源分子。双膦酸类药物是一种广泛用于治疗多种代谢性骨病的抗代谢药物。唑来膦(ZA)是一种含氮双膦酸盐(N-BP)，是临床批准的双膦酸类药物中效力最强的一种。在接受长期N-BP治疗的患者中，已有报道双膦酸致颌骨坏死的病例。然而，骨坏死不会发生在长骨中。本研究的目的是利用先前建立的不稳定的胫骨骨折模型和新的下颌骨骨折修复模型，比较唑来膦酸盐对长骨和颅骨再生的影响。与主要通过软骨内骨化愈合的胫骨骨折相反，下颌骨骨折通过软骨内和膜内骨化愈合，与胫骨骨折相比，软骨内骨化程度较轻。在胫骨修复的早期阶段，ZA减少了骨痂和软骨的形成。同时，我们发现在软骨痂修复阶段，软骨肥大的延迟和血管生成的减少。在修复的后期，ZA延缓了骨痂、软骨和骨的重塑。在下颌骨中，ZA延迟了骨痂、软骨和骨重建，并与软骨痂和硬骨痂修复过程中破骨细胞数量减少有关。这些结果揭示了与胫骨相比，ZA对下颌骨软骨和骨重塑的影响更深远。这可能使下颌骨在疾病条件下易受ZA的不利影响。这些结果还表明，ZA的治疗效果可能需要在颅骨和长骨中使用时间和剂量特定的治疗方法来优化。
Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate (N-BP), is the most potent bisphosphonate among the clinically approved bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis does not occur in long bones. The aim of this study was to compare the effects of zoledronate on long bone and cranial bone regeneration using a previously established model of non-stabilized tibial fractures and a new model of mandibular fracture repair. Contrary to tibial fractures, which heal mainly through endochondral ossification, mandibular fractures healed via endochondral and intramembranous ossification with a lesser degree of endochondral ossification compared to tibial fractures. In the tibia, ZA reduced callus and cartilage formation during the early stages of repair. In parallel, we found a delay in cartilage hypertrophy and a decrease in angiogenesis during the soft callus phase of repair. During later stages of repair, ZA delayed callus, cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and bone remodeling in correlation with a decrease in osteoclast number during the soft and hard callus phases of repair. These results reveal a more profound impact of ZA on cartilage and bone remodeling in the mandible compared to the tibia. This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones.
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DOI：
10.2174/1874325000903010083
发表时间：
2009-10-01
期刊：
The open orthopaedics journal
影响因子：
--
作者：
Evans KD;Oberbauer AM
通讯作者：
Oberbauer AM
影响因子：
2
作者：
Gundersen, HJG;Jensen, EBV;Nielsen, J
通讯作者：
Nielsen, J
影响因子：
4.1
作者：
Lesclous, Philippe;Najm, Semaan Abi;Samson, Jacky
通讯作者：
Samson, Jacky
影响因子：
3.6
作者：
D'Aoust, P;McCulloch, CAG;Lekic, PC
通讯作者：
Lekic, PC
影响因子：
6.2
作者：
Hoff, Ana O.;Toth, Bela B.;Hortobagyi, Gabriel N.
通讯作者：
Hortobagyi, Gabriel N.