Meesters Dennis M, Wijnands Karolina A P, van Eijk Hans M H, Hofman Martijn, Hildebrand Frank, Verbruggen Jan P A M, Brink Peter R G, Poeze Martijn
Department of Surgery, Division of Trauma Surgery, Maastricht University Medical Center +, 6200 MD Maastricht, The Netherlands.
NUTRIM School for Nutrition and Translational Research in Metabolism, 6200 MD Maastricht, The Netherlands.
Biomedicines. 2022 Oct 3;10(10):2474. doi: 10.3390/biomedicines10102474.
Fracture healing and nonunion development are influenced by a range of biological factors. Adequate amino acid concentrations, especially arginine, are known to be important during normal bone healing. We hypothesize that bone arginine availability in autologous bone marrow grafting, when using the reamer-irrigator-aspirator (RIA) procedure, is a marker of bone healing capacity in patients treated for nonunion. Seventeen patients treated for atrophic long bone nonunion by autologous bone grafting by the RIA procedure were included and divided into two groups, successful treatment of nonunion and unsuccessful, and were compared with control patients after normal fracture healing. Reamed bone marrow aspirate from a site distant to the nonunion was obtained and the amino acids and enzymes relevant to arginine metabolism were measured. Arginine and ornithine concentrations were higher in patients with successful bone healing after RIA in comparison with unsuccessful healing. Ornithine concentrations and arginase-1 expression were lower in all nonunion patients compared to control patients, while citrulline concentrations were increased. Nitric oxide synthase 2 () expression was significantly increased in all RIA-treated patients, and higher in patients with a successful outcome when compared with an unsuccessful outcome. The results indicate an influence of the arginine-nitric oxide metabolism in collected bone marrow, on the outcome of nonunion treatment, with indications for a prolonged inflammatory response in patients with unsuccessful bone grafting therapy. The determination of arginine concentrations and expression could be used as a predictor for the successful treatment of autologous bone grafting in nonunion treatment.
骨折愈合和骨不连的发生受到一系列生物学因素的影响。已知充足的氨基酸浓度,尤其是精氨酸,在正常骨愈合过程中很重要。我们推测,在采用扩髓-冲洗-吸引器(RIA)技术进行自体骨髓移植时,骨中精氨酸的可利用性是骨不连患者骨愈合能力的一个指标。纳入了17例采用RIA技术进行自体骨移植治疗萎缩性长骨骨不连的患者,并将其分为骨不连治疗成功组和失败组,与骨折正常愈合后的对照患者进行比较。获取远离骨不连部位的扩髓骨髓抽吸物,测量与精氨酸代谢相关的氨基酸和酶。与愈合失败的患者相比,RIA术后骨愈合成功的患者精氨酸和鸟氨酸浓度更高。与对照患者相比,所有骨不连患者的鸟氨酸浓度和精氨酸酶-1表达均较低,而瓜氨酸浓度升高。所有接受RIA治疗的患者中一氧化氮合酶2()表达均显著增加,治疗成功的患者比失败的患者更高。结果表明,采集的骨髓中精氨酸-一氧化氮代谢对骨不连治疗结果有影响,提示骨移植治疗失败的患者存在炎症反应延长的情况。精氨酸浓度和表达的测定可作为骨不连治疗中自体骨移植成功治疗的预测指标。