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

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...

Full description

Bibliographic Details
Main Authors: Dennis M. Meesters, Karolina A. P. Wijnands, Hans M. H. van Eijk, Martijn Hofman, Frank Hildebrand, Jan P. A. M. Verbruggen, Peter R. G. Brink, Martijn Poeze
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/10/2474
_version_ 1797475061716746240
author Dennis M. Meesters
Karolina A. P. Wijnands
Hans M. H. van Eijk
Martijn Hofman
Frank Hildebrand
Jan P. A. M. Verbruggen
Peter R. G. Brink
Martijn Poeze
author_facet Dennis M. Meesters
Karolina A. P. Wijnands
Hans M. H. van Eijk
Martijn Hofman
Frank Hildebrand
Jan P. A. M. Verbruggen
Peter R. G. Brink
Martijn Poeze
author_sort Dennis M. Meesters
collection DOAJ
description 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 (<i>Nos2</i>) 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 <i>Nos2</i> expression could be used as a predictor for the successful treatment of autologous bone grafting in nonunion treatment.
first_indexed 2024-03-09T20:38:47Z
format Article
id doaj.art-4babd6b2117d4ad49c752ca2a8412364
institution Directory Open Access Journal
issn 2227-9059
language English
last_indexed 2024-03-09T20:38:47Z
publishDate 2022-10-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj.art-4babd6b2117d4ad49c752ca2a84123642023-11-23T23:03:38ZengMDPI AGBiomedicines2227-90592022-10-011010247410.3390/biomedicines10102474Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion HealingDennis M. Meesters0Karolina A. P. Wijnands1Hans M. H. van Eijk2Martijn Hofman3Frank Hildebrand4Jan P. A. M. Verbruggen5Peter R. G. Brink6Martijn Poeze7Department of Surgery, Division of Trauma Surgery, Maastricht University Medical Center +, 6200 MD Maastricht, The NetherlandsDepartment of Surgery, Division of Trauma Surgery, Maastricht University Medical Center +, 6200 MD Maastricht, The NetherlandsDepartment of Surgery, Division of Trauma Surgery, Maastricht University Medical Center +, 6200 MD Maastricht, The NetherlandsDepartment of Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, 52074 Aachen, GermanyDepartment of Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, 52074 Aachen, GermanyDepartment of Surgery, Division of Trauma Surgery, Maastricht University Medical Center +, 6200 MD Maastricht, The NetherlandsDepartment of Surgery, Division of Trauma Surgery, Maastricht University Medical Center +, 6200 MD Maastricht, The NetherlandsDepartment of Surgery, Division of Trauma Surgery, Maastricht University Medical Center +, 6200 MD Maastricht, The NetherlandsFracture 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 (<i>Nos2</i>) 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 <i>Nos2</i> expression could be used as a predictor for the successful treatment of autologous bone grafting in nonunion treatment.https://www.mdpi.com/2227-9059/10/10/2474nonunionautologous bone graftingnitric oxideargininecitrulline
spellingShingle Dennis M. Meesters
Karolina A. P. Wijnands
Hans M. H. van Eijk
Martijn Hofman
Frank Hildebrand
Jan P. A. M. Verbruggen
Peter R. G. Brink
Martijn Poeze
Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing
Biomedicines
nonunion
autologous bone grafting
nitric oxide
arginine
citrulline
title Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing
title_full Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing
title_fullStr Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing
title_full_unstemmed Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing
title_short Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing
title_sort arginine availability in reamed intramedullary aspirate as predictor of outcome in nonunion healing
topic nonunion
autologous bone grafting
nitric oxide
arginine
citrulline
url https://www.mdpi.com/2227-9059/10/10/2474
work_keys_str_mv AT dennismmeesters arginineavailabilityinreamedintramedullaryaspirateaspredictorofoutcomeinnonunionhealing
AT karolinaapwijnands arginineavailabilityinreamedintramedullaryaspirateaspredictorofoutcomeinnonunionhealing
AT hansmhvaneijk arginineavailabilityinreamedintramedullaryaspirateaspredictorofoutcomeinnonunionhealing
AT martijnhofman arginineavailabilityinreamedintramedullaryaspirateaspredictorofoutcomeinnonunionhealing
AT frankhildebrand arginineavailabilityinreamedintramedullaryaspirateaspredictorofoutcomeinnonunionhealing
AT janpamverbruggen arginineavailabilityinreamedintramedullaryaspirateaspredictorofoutcomeinnonunionhealing
AT peterrgbrink arginineavailabilityinreamedintramedullaryaspirateaspredictorofoutcomeinnonunionhealing
AT martijnpoeze arginineavailabilityinreamedintramedullaryaspirateaspredictorofoutcomeinnonunionhealing