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骨质疏松症及其治疗对骨折愈合的影响:动物与临床研究的系统评价

The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies.

作者信息

Gorter E A, Reinders C R, Krijnen P, Appelman-Dijkstra N M, Schipper I B

机构信息

Leiden University Medical Center, Departments of Trauma Surgery, P. O. Box 9600, 2300 RC Leiden, the Netherlands.

Internal Medicine, Center for Bone Quality, P. O. Box 9600, 2300 RC Leiden, the Netherlands.

出版信息

Bone Rep. 2021 Aug 16;15:101117. doi: 10.1016/j.bonr.2021.101117. eCollection 2021 Dec.

Abstract

INTRODUCTION

Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone structure. Its treatment is directed at the processes of bone formation or resorption, that are of utmost importance in fracture healing. We provide a comprehensive review of the literature aiming to summarize and clarify the effects of osteoporosis and its treatment on fracture healing.

MATERIAL AND METHODS

A literature search was conducted in PubMed and Embase (OVID version). In vivo animal and human studies on long bone fractures were included. A total of 93 articles were included for this review; 23 studies on the effect of osteoporosis (18 animal and 5 clinical studies) and 70 studies on the effect of osteoporosis treatment (41 animal, 26 clinical studies and 3 meta-analyses) on fracture healing.

RESULTS

In animal fracture models osteoporosis was associated with decreased callus formation and bone growth, bone mineral density, biomechanical strength and delayed cellular and differentiation processes during fracture healing. Two large databases identified osteoporosis as a risk factor for non-union whereas three other studies did not. One of those three studies however found a prolonged healing time in patients with osteoporosis. Anti-osteoporosis medication showed inconsistent effects on fracture healing in both non-osteoporotic and osteoporotic animal models. Only the parathyroid hormone and anti-resorption medication were related to improved fracture healing and delayed remodelling respectively. Clinical studies performed in predominantly hip and distal radius fracture patients showed no effect of bisphosphonates on fracture healing. Parathyroid hormone reduced time to union in several clinical trials performed in mainly hip fracture patients, but this did not result in decreased delayed or non-union rates.

CONCLUSION

Evidence that substantiates the negative influence of osteoporosis on fracture healing is predominantly from animal studies and to a lesser extent from clinical studies, since convincing clinical evidence lacks. Bisphosphonates and parathyroid hormone may be used during fracture healing, since no clear negative effect has been shown. Parathyroid hormone might even decrease time to fracture union, without decreasing union rate.

摘要

引言

骨质疏松症的特征是骨量低和骨结构微观结构退化。其治疗针对骨形成或骨吸收过程,这些过程在骨折愈合中至关重要。我们对文献进行了全面综述,旨在总结和阐明骨质疏松症及其治疗对骨折愈合的影响。

材料与方法

在PubMed和Embase(OVID版本)中进行文献检索。纳入了关于长骨骨折的体内动物和人体研究。本综述共纳入93篇文章;23项关于骨质疏松症影响的研究(18项动物研究和5项临床研究)以及70项关于骨质疏松症治疗对骨折愈合影响的研究(41项动物研究、26项临床研究和3项荟萃分析)。

结果

在动物骨折模型中,骨质疏松症与骨痂形成减少、骨生长、骨矿物质密度、生物力学强度降低以及骨折愈合过程中细胞和分化过程延迟有关。两个大型数据库将骨质疏松症确定为骨不连的危险因素,而其他三项研究则未发现。然而,这三项研究中的一项发现骨质疏松症患者的愈合时间延长。抗骨质疏松药物在非骨质疏松和骨质疏松动物模型中对骨折愈合的影响不一致。只有甲状旁腺激素和抗吸收药物分别与骨折愈合改善和重塑延迟有关。主要在髋部和桡骨远端骨折患者中进行的临床研究表明,双膦酸盐对骨折愈合没有影响。甲状旁腺激素在主要针对髋部骨折患者进行的多项临床试验中缩短了愈合时间,但这并未导致延迟愈合或骨不连率降低。

结论

证实骨质疏松症对骨折愈合有负面影响的证据主要来自动物研究,临床研究较少,因为缺乏令人信服的临床证据。双膦酸盐和甲状旁腺激素可在骨折愈合期间使用,因为尚未显示出明显的负面影响。甲状旁腺激素甚至可能缩短骨折愈合时间,而不降低愈合率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cc8/8379440/671e71287d97/gr1.jpg

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