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. 2022 Oct 3;10(10):2474.
doi: 10.3390/biomedicines10102474.

Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing

Dennis M Meesters  1   2 , Karolina A P Wijnands  1   2 , Hans M H van Eijk  1   2 , Martijn Hofman  3 , Frank Hildebrand  3 , Jan P A M Verbruggen  1 , Peter R G Brink  1 , Martijn Poeze  1   2
Affiliations

Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing

Dennis M Meesters et al. Biomedicines. .

Abstract

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 (Nos2) 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 Nos2 expression could be used as a predictor for the successful treatment of autologous bone grafting in nonunion treatment.

Keywords: arginine; autologous bone grafting; citrulline; nitric oxide; nonunion.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Concentrations of arginine (panel A), citrulline (B) and ornithine (C) in reamed intramedullary aspirate, presented as µmol/mg wet tissue. Results in control tissues are presented in the white bars. Samples obtained from patients with a primary successful RIA treatment are shown in orange and with an unsuccessful treatment in dark blue. *: p < 0.05; *** p < 0.001 and ****: p < 0.0001.
Figure 2
Figure 2
Relative expression of iNOS (Nos2, inducible nitric oxide synthase, panel (A)) and Arginase-1 (Arg1, panel (B)). Results in control tissue are represented in white bars. Samples obtained from patients with subsequently successful RIA treatment are shown in orange. The failure of the treatment group is presented in dark blue. Levels of significance: *: p < 0.05 and ***: p < 0.001).
See this image and copyright information in PMC

References

    1. Mills L.A., Aitken S.A., Simpson A. The risk of non-union per fracture: Current myths and revised figures from a population of over 4 million adults. Acta Orthop. 2017;88:434–439. doi: 10.1080/17453674.2017.1321351. - DOI - PMC - PubMed
    1. Bishop J.A., Palanca A.A., Bellino M.J., Lowenberg D.W. Assessment of compromised fracture healing. J. Am. Acad. Orthop. Surg. 2012;20:273–282. doi: 10.5435/JAAOS-20-05-273. - DOI - PubMed
    1. Karladani A.H., Granhed H., Karrholm J., Styf J. The influence of fracture etiology and type on fracture healing: A review of 104 consecutive tibial shaft fractures. Arch. Orthop. Trauma Surg. 2001;121:325–328. doi: 10.1007/s004020000252. - DOI - PubMed
    1. Kanakaris N.K., Giannoudis P.V. The health economics of the treatment of long-bone non-unions. Injury. 2007;38((Suppl. S2)):S77–S84. doi: 10.1016/S0020-1383(07)80012-X. - DOI - PubMed
    1. Giannoudis P.V., Einhorn T.A., Marsh D. Fracture healing: The diamond concept. Injury. 2007;38((Suppl. S4)):S3–S6. doi: 10.1016/S0020-1383(08)70003-2. - DOI - PubMed