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Research

ENHANCEMENT OF FRACTURE HEALING BY AMINO ACIDS LYSINE AND ARGININE: AN EXPERIMENTAL STUDY IN RABBITS

8th Combined Meeting Of Orthopaedic Research Societies (CORS)



Abstract

Introduction

Amino acids like arginine and lysine have been suggested to hasten the process of fracture healing by improving the local blood supply, supplementing growth factors, and improving collagen synthesis. We studied the role of lysine and arginine in the fracture repair process with regard to the rate of healing, probable mechanisms involved in the process, and mutual synergism between these agents.

Materials and methods

In an experimental study, 40 rabbits were subjected to ulnar osteotomy. They were distributed in control (14) and test groups (26). Twenty-six animals in the test group were fed with a diet rich in lysine and arginine. Both the groups were followed radiologically and histologically till union.

Results

Ten weeks postoperatively, there was difference evident radiologically between those supplemented with lysine and arginine, indicating that these components enhance the healing in the later part of bone remodeling, canal restoration, and medullary as well as cortical continuity and repair. X-rays obtained at weeks 9, 10, and 12 in both the groups showed statistical significance. These findings showed that healing is better in the test group in terms of increased vascularity in the early part of healing, i.e., at approx. 2–3 weeks and in terms of bone matrix, Haversian system formation, and cortical repair in the later part of healing, i.e., at approx. 9–12 weeks between the two groups. There was better healing of osteotomy in terms of better vascularization, callus formation, and mineralization in the test group. The time of healing in the test group was reduced by a period of 2 weeks.

Discussion

NO is expressed during fracture healing in rats and humans, as after fracture, mRNA, protein, and enzymatic activity iNOS have been identified at the fracture callus with maximum activity at day 15. Thus, the initial better healing, by 3 weeks, in the test group rabbits can be explained by the fact that the iNOS activity mediates an increased vascularity at the fracture site. The mRNA activity for eNOS and bNOS was induced slightly later than that for iNOS, which was consistent with a temporal increase in the calcium-dependent NOS activity that gradually increased up to day 30. All calcium-dependent processes like collagen recruitment for Haversian system formation, better bone matrix, and cortical repair were significantly better at any point of time, in the rabbits that were supplemented with arginine; however, lysine has also an important role in these processes. Arginine may influence bone formation by enhancing local IGF-I production. Nitric oxide (NO), an EC mediator, has been reported to be antigenic as well as proangiogenic in different models of in vivo angiogenesis. Arginine being nitric oxide donor increases angiogenesis.

Summary

Amino acids like arginine and lysine may hasten fracture healing. Adjuvant amino acid treatment is having inherent advantage in being nontoxic, inexpensive, and a simple oral therapy.