Academic Unit of Trauma and Orthopaedic Surgery, LIMM Section Musculoskeletal Disease, Clarendon Wing, Leeds Teaching Hospitals NHS Trust, Great George Street, Leeds LS1 3EX, UK.
BMC Musculoskelet Disord. 2011 Feb 10;12:44. doi: 10.1186/1471-2474-12-44.
Despite the known multi-factorial nature of atrophic fracture non-unions, a possible genetic predisposition for the development of this complication after long bone fractures remains unknown. This pilot study aimed to address this issue by performing a preliminary SNP analysis of specific genes known to regulate fracture healing.
A total of fifteen SNPs within four genes of the Bone Morphogenetic Protein (BMP) pathway (BMP-2, BMP-7, NOGGIN and SMAD6) were examined, in 109 randomly selected patients with long bone fractures as a result of motor vehicle accident, fall or direct blow. There were sixty-two patients with atrophic non-union and forty-seven patients (54 fractures) with uneventful fracture union. Overall SNPs frequencies were computed with respect to patient's age, gender, smoking habits, fracture-associated parameters and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and tested for their association to the impaired bone healing process, using binary logistic regression (STATA 11.1; StataCorp, Texas USA).
Statistical analysis revealed age to be an important covariate in the development of atrophic non-union (p = 0.01, OR 1.05 [per year]), and two specific genotypes (G/G genotype of the rs1372857 SNP, located on NOGGIN and T/T genotype of the rs2053423 SNP, located on SMAD6) to be associated with a greater risk of fracture non-union (p = 0.02, OR 4.56 and p = 0.04, OR 10.27, respectively, after adjustment for age).
This is the first clinical study to investigate the potential existence of genetic susceptibility to fracture non-union. Even though no concrete conclusions can be obtained from this pilot study, our results indicate the existence of a potential genetically predetermined impairment within the BMP signalling cascade, initiated after a fracture and when combined with other risk factors could synergistically increase the susceptibility of a patient to develop non-union. Further research is desirable in order to clarify the genetic component and its role and interaction with other risk factors in the development of atrophic long bone non-union, as simple genetic testing may contribute to the early identification of patients at risk in the future and the on-time intervention at the biologic aspects of bone healing.
尽管萎缩性骨折不愈合的多因素性质是已知的，但长骨骨折后发生这种并发症的潜在遗传易感性尚不清楚。这项初步研究旨在通过对已知调节骨折愈合的特定基因进行 SNP 分析来解决这个问题。
在因车祸、摔倒或直接撞击导致长骨骨折的 109 名随机患者中，共检查了骨形态发生蛋白（BMP）途径中的四个基因（BMP-2、BMP-7、NOGGIN 和 SMAD6）中的 15 个 SNP。其中 62 例为萎缩性骨不愈合，47 例（54 例骨折）为无并发症骨愈合。根据患者的年龄、性别、吸烟习惯、骨折相关参数和非甾体抗炎药（NSAIDs）的使用情况，计算了总体 SNP 频率，并使用二元逻辑回归（STATA 11.1；StataCorp，美国德克萨斯州）对其与受损骨愈合过程的关系进行了检验。
统计分析显示，年龄是导致萎缩性骨不愈合的一个重要协变量（p = 0.01，OR 1.05[每增加 1 年]），并且两种特定的基因型（位于 NOGGIN 的 rs1372857 SNP 的 G/G 基因型和位于 SMAD6 的 rs2053423 SNP 的 T/T 基因型）与骨折不愈合的风险增加相关（调整年龄后，p = 0.02，OR 4.56；p = 0.04，OR 10.27）。
这是第一项研究骨折不愈合遗传易感性的临床研究。尽管从这项初步研究中无法得出具体结论，但我们的结果表明，BMP 信号级联中存在一种潜在的遗传决定的损伤，这种损伤在骨折后发生，并与其他危险因素结合时，可能会协同增加患者发生不愈合的易感性。需要进一步研究以阐明遗传因素及其在萎缩性长骨不愈合中的作用和与其他危险因素的相互作用，因为简单的遗传测试可能有助于未来早期识别有风险的患者，并及时干预骨折愈合的生物学方面。
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