Excess Dietary Methionine Does Not Affect Fracture Healing in Mice

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2012 Dec 1

PMID 23197225

Citations 1

Authors

Joerg H Holstein

Julia Schmalenbach

Markus Herrmann

Ilona Olku

Patric Garcia

Tina Histing

Wolfgang Herrmann

Michael D Menger

Tim Pohlemann

Lutz Claes

Affiliations

Soon will be listed here.

Abstract

Background: An elevated serum concentration of homocysteine (hyperhomocysteinemia) has been shown to disturb fracture healing. As the essential amino acid, methionine, is a precursor of homocysteine, we aimed to investigate whether excess methionine intake affects bone repair.

Material/methods: We analyzed bone repair in 2 groups of mice. One group was fed a methionine-rich diet (n=13), and the second group received an equicaloric control diet without methionine supplementation (n=12). Using a closed femoral fracture model, bone repair was analyzed by histomorphometry and biomechanical testing at 4 weeks after fracture. Blood was sampled to measure serum concentrations of homocysteine, the bone formation marker osteocalcin, and the bone resorption marker collagen I C-terminal crosslaps

Results: Serum concentrations of homocysteine were significantly higher in the methionine group than in the control group, while serum markers of bone turnover did not differ significantly between the 2 groups. Histomorphometry revealed no significant differences in size and tissue composition of the callus between animals fed the methionine-enriched diet and those receiving the control diet. Accordingly, animals of the 2 groups showed a comparable bending stiffness of the healing bones.

Conclusions: We conclude that excess methionine intake causes hyperhomocysteinemia, but does not affect fracture healing in mice.

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References

Thaler R, Spitzer S, Rumpler M, Fratzl-Zelman N, Klaushofer K, Paschalis E . Differential effects of homocysteine and beta aminopropionitrile on preosteoblastic MC3T3-E1 cells. Bone. 2009; 46(3):703-9. DOI: 10.1016/j.bone.2009.10.038. View

Ward M, McNulty H, Pentieva K, McPartlin J, Strain J, Weir D . Fluctuations in dietary methionine intake do not alter plasma homocysteine concentration in healthy men. J Nutr. 2000; 130(11):2653-7. DOI: 10.1093/jn/130.11.2653. View

Herrmann M, Umanskaya N, Wildemann B, Colaianni G, Widmann T, Zallone A . Stimulation of osteoblast activity by homocysteine. J Cell Mol Med. 2008; 12(4):1205-10. PMC: 3865664. DOI: 10.1111/j.1582-4934.2008.00104.x. View

Joosten E, Pelemans W, Devos P, Lesaffre E, Goossens W, Criel A . Cobalamin absorption and serum homocysteine and methylmalonic acid in elderly subjects with low serum cobalamin. Eur J Haematol. 1993; 51(1):25-30. DOI: 10.1111/j.1600-0609.1993.tb00600.x. View

Troen A, Lutgens E, Smith D, Rosenberg I, Selhub J . The atherogenic effect of excess methionine intake. Proc Natl Acad Sci U S A. 2003; 100(25):15089-94. PMC: 299913. DOI: 10.1073/pnas.2436385100. View

Holstein J, Herrmann M, Schmalenbach J, Obeid R, Olku I, Klein M . Deficiencies of folate and vitamin B12 do not affect fracture healing in mice. Bone. 2010; 47(1):151-5. DOI: 10.1016/j.bone.2010.04.592. View

Koh J, Lee Y, Kim Y, Kim D, Kim H, Park J . Homocysteine enhances bone resorption by stimulation of osteoclast formation and activity through increased intracellular ROS generation. J Bone Miner Res. 2006; 21(7):1003-11. DOI: 10.1359/jbmr.060406. View

Shimakawa T, Nieto F, MALINOW M, Chambless L, Schreiner P, Szklo M . Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults. Ann Epidemiol. 1997; 7(4):285-93. DOI: 10.1016/s1047-2797(97)00004-5. View

Ubbink J, Vermaak W, Van der Merwe A, Becker P . The effect of blood sample aging and food consumption on plasma total homocysteine levels. Clin Chim Acta. 1992; 207(1-2):119-28. DOI: 10.1016/0009-8981(92)90155-j. View

10.

Holstein J, Matthys R, Histing T, Becker S, Fiedler M, Garcia P . Development of a stable closed femoral fracture model in mice. J Surg Res. 2008; 153(1):71-5. DOI: 10.1016/j.jss.2008.02.042. View

11.

Claes L, Schmalenbach J, Herrmann M, Olku I, Garcia P, Histing T . Hyperhomocysteinemia is associated with impaired fracture healing in mice. Calcif Tissue Int. 2009; 85(1):17-21. DOI: 10.1007/s00223-009-9262-6. View

12.

Megas P, Panagiotis M . Classification of non-union. Injury. 2005; 36 Suppl 4:S30-7. DOI: 10.1016/j.injury.2005.10.008. View

13.

Ditscheid B, Funfstuck R, Busch M, Schubert R, Gerth J, Jahreis G . Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study. Eur J Clin Nutr. 2005; 59(6):768-75. DOI: 10.1038/sj.ejcn.1602138. View

14.

Vaes B, Lute C, van der Woning S, Piek E, Vermeer J, Blom H . Inhibition of methylation decreases osteoblast differentiation via a non-DNA-dependent methylation mechanism. Bone. 2009; 46(2):514-23. DOI: 10.1016/j.bone.2009.09.033. View

15.

Herrmann M, Schmidt J, Umanskaya N, Wagner A, Taban-Shomal O, Widmann T . The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med. 2007; 45(12):1621-32. DOI: 10.1515/CCLM.2007.362. View

16.

Verhoef P, Stampfer M, Buring J, Gaziano J, Allen R, Stabler S . Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol. 1996; 143(9):845-59. DOI: 10.1093/oxfordjournals.aje.a008828. View

17.

Herrmann W, Herrmann M, Obeid R . Hyperhomocysteinaemia: a critical review of old and new aspects. Curr Drug Metab. 2007; 8(1):17-31. DOI: 10.2174/138920007779315008. View

18.

Rodriguez-Merchan E, Forriol F . Nonunion: general principles and experimental data. Clin Orthop Relat Res. 2004; (419):4-12. View

19.

Holstein J, Garcia P, Histing T, Kristen A, Scheuer C, Menger M . Advances in the establishment of defined mouse models for the study of fracture healing and bone regeneration. J Orthop Trauma. 2009; 23(5 Suppl):S31-8. DOI: 10.1097/BOT.0b013e31819f27e5. View

20.

Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes J . DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med. 2003; 41(11):1392-403. DOI: 10.1515/CCLM.2003.214. View