Skip to main content
Top
Published in: Osteoporosis International 1/2013

01-01-2013 | Short Communication

Associations of homoarginine with bone metabolism and density, muscle strength and mortality: cross-sectional and prospective data from 506 female nursing home patients

Authors: S. Pilz, A. Meinitzer, A. Tomaschitz, K. Kienreich, H. Dobnig, M. Schwarz, D. Wagner, C. Drechsler, C. Piswanger-Sölkner, W. März, A. Fahrleitner-Pammer

Published in: Osteoporosis International | Issue 1/2013

Login to get access

Abstract

Summary

In female nursing home patients, homoarginine was associated with lower bone turnover, higher bone density, lower mortality and, by trend, with muscle strength.

Introduction

Homoarginine, a cationic amino acid, may be relevant for muscusloskeletal health because it inhibits alkaline phosphatases (AP) and is involved in nitric oxide and energy metabolism. We aimed to evaluate whether homoarginine serum concentrations are associated with bone density and metabolism, muscle strength, fractures and mortality.

Methods

We examined a cohort of female nursing home patients that underwent quantitative bone ultrasound (QUS) measurements and assessments of knee extensor strength. Measurements of serum homoarginine, C-terminal telopeptide cross-links (β-CTxs) and osteocalcin were also performed at baseline. Thereafter, patients were followed-up with respect to fractures and mortality.

Results

Serum homoarginine concentrations were determined in 506 female study participants (mean age: 83.9 ± 6.0 years). Homoarginine was inversely correlated with β-CTxs (r = −0.26; p < 0.001) and osteocalcin (r = −0.21; p < 0.001), and these associations remained significant in multiple regression analyses. Multivariate regression analyses showed that homoarginine is significantly associated with calcaneus stiffness (beta coefficient = 0.11; p = 0.020) and by trend with knee extensor strength (beta coefficient = 0.09; p = 0.065). During a mean follow-up time of 27 ± 8 months, we recorded 119 deaths (23.5%) and 63 fractures (12.5%). In multivariate analyses, homoarginine was associated with significantly reduced risk of mortality and the combined endpoint of fractures and mortality.

Conclusions

Whether homoarginine metabolism is critically involved into the pathogenesis of musculoskeletal diseases and fatal events warrants further studies.
Literature
1.
go back to reference Jesudason D, Clifton P (2011) The interaction between dietary protein and bone health. J Bone Miner Metab 29(1):1–14PubMedCrossRef Jesudason D, Clifton P (2011) The interaction between dietary protein and bone health. J Bone Miner Metab 29(1):1–14PubMedCrossRef
2.
go back to reference Wallimann T, Tokarska-Schlattner M, Schlattner U (2011) The creatine kinase system and pleiotropic effects of creatine. Amino Acids 40(5):1271–96PubMedCrossRef Wallimann T, Tokarska-Schlattner M, Schlattner U (2011) The creatine kinase system and pleiotropic effects of creatine. Amino Acids 40(5):1271–96PubMedCrossRef
3.
go back to reference Meinitzer A, Drechsler C, Tomaschitz A, Pilz S, Krane V, Wanner C, März W (2011) Homoarginine: a new cardiovascular risk marker in hemodialysis patients. J Lab Med 35(3):153–159 Meinitzer A, Drechsler C, Tomaschitz A, Pilz S, Krane V, Wanner C, März W (2011) Homoarginine: a new cardiovascular risk marker in hemodialysis patients. J Lab Med 35(3):153–159
4.
go back to reference Ryan WL, Wells IC (1964) Homocitrulline and homoarginine synthesis from lysine. Science 144:1122–7PubMedCrossRef Ryan WL, Wells IC (1964) Homocitrulline and homoarginine synthesis from lysine. Science 144:1122–7PubMedCrossRef
5.
go back to reference Magnusson P, Farley JR (2002) Differences in sialic acid residues among bone alkaline phosphatase isoforms: a physical, biochemical, and immunological characterization. Calcif Tissue Int 71(6):508–18PubMedCrossRef Magnusson P, Farley JR (2002) Differences in sialic acid residues among bone alkaline phosphatase isoforms: a physical, biochemical, and immunological characterization. Calcif Tissue Int 71(6):508–18PubMedCrossRef
6.
go back to reference Kozlenkov A, Le Du MH, Cuniasse P, Ny T, Hoylaerts MF, Millán JL (2004) Residues determining the binding specificity of uncompetitive inhibitors to tissue-nonspecific alkaline phosphatase. J Bone Miner Res 19(11):1862–72PubMedCrossRef Kozlenkov A, Le Du MH, Cuniasse P, Ny T, Hoylaerts MF, Millán JL (2004) Residues determining the binding specificity of uncompetitive inhibitors to tissue-nonspecific alkaline phosphatase. J Bone Miner Res 19(11):1862–72PubMedCrossRef
7.
go back to reference Valtonen P, Laitinen T, Lyyra-Laitinen T, Raitakari OT, Juonala M, Viikari JS, Heiskanen N, Vanninen E, Punnonen K, Heinonen S (2008) Serum L-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation. Circ J 72(11):1879–84PubMedCrossRef Valtonen P, Laitinen T, Lyyra-Laitinen T, Raitakari OT, Juonala M, Viikari JS, Heiskanen N, Vanninen E, Punnonen K, Heinonen S (2008) Serum L-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation. Circ J 72(11):1879–84PubMedCrossRef
8.
go back to reference Saura M, Tarin C, Zaragoza C (2010) Recent insights into the implication of nitric oxide in osteoblast differentiation and proliferation during bone development. ScientificWorldJournal 10:624–32PubMedCrossRef Saura M, Tarin C, Zaragoza C (2010) Recent insights into the implication of nitric oxide in osteoblast differentiation and proliferation during bone development. ScientificWorldJournal 10:624–32PubMedCrossRef
10.
go back to reference März W, Meinitzer A, Drechsler C, Pilz S, Krane V, Kleber ME, Fischer J, Winkelmann BR, Böhm BO, Ritz E, Wanner C (2010) Homoarginine, cardiovascular risk, and mortality. Circulation 122(10):967–75PubMedCrossRef März W, Meinitzer A, Drechsler C, Pilz S, Krane V, Kleber ME, Fischer J, Winkelmann BR, Böhm BO, Ritz E, Wanner C (2010) Homoarginine, cardiovascular risk, and mortality. Circulation 122(10):967–75PubMedCrossRef
11.
go back to reference Pilz S, Tomaschitz A, Meinitzer A, Drechsler C, Ritz E, Krane V, Wanner C, Böhm BO, März W (2011) Low serum homoarginine is a novel risk factor for fatal strokes in patients undergoing coronary angiography. Stroke 42(4):1132–4PubMedCrossRef Pilz S, Tomaschitz A, Meinitzer A, Drechsler C, Ritz E, Krane V, Wanner C, Böhm BO, März W (2011) Low serum homoarginine is a novel risk factor for fatal strokes in patients undergoing coronary angiography. Stroke 42(4):1132–4PubMedCrossRef
12.
go back to reference Pilz S, Meinitzer A, Tomaschitz A, Drechsler C, Ritz E, Krane V, Wanner C, Boehm BO, März W (2011) Low homoarginine concentration is a novel risk factor for heart disease. Heart 97(15):1222–7PubMedCrossRef Pilz S, Meinitzer A, Tomaschitz A, Drechsler C, Ritz E, Krane V, Wanner C, Boehm BO, März W (2011) Low homoarginine concentration is a novel risk factor for heart disease. Heart 97(15):1222–7PubMedCrossRef
13.
go back to reference Drechsler C, Meinitzer A, Pilz S, Krane V, Tomaschitz A, Ritz E, März W, Wanner C (2011) Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients. Eur J Heart Fail 13(8):852–9PubMedCrossRef Drechsler C, Meinitzer A, Pilz S, Krane V, Tomaschitz A, Ritz E, März W, Wanner C (2011) Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients. Eur J Heart Fail 13(8):852–9PubMedCrossRef
14.
go back to reference Köttgen A, Glazer NL, Dehghan A, Hwang SJ, Katz R, Li M, Li M, Yang Q, Gudnason V, Launer LJ, Harris TB, Smith AV, Arking DE, Astor BC, Boerwinkle E, Ehret GB, Ruczinski I, Scharpf RB, Chen YD, de Boer IH, Haritunians T, Lumley T, Sarnak M, Siscovick D, Benjamin EJ, Levy D, Upadhyay A, Aulchenko YS, Hofman A, Rivadeneira F, Uitterlinden AG, van Duijn CM, Chasman DI, Paré G, Ridker PM, Kao WH, Witteman JC, Coresh J, Shlipak MG, Fox CS (2009) Multiple loci associated with indices of renal function and chronic kidney disease. Nat Genet 41(6):712–717PubMedCrossRef Köttgen A, Glazer NL, Dehghan A, Hwang SJ, Katz R, Li M, Li M, Yang Q, Gudnason V, Launer LJ, Harris TB, Smith AV, Arking DE, Astor BC, Boerwinkle E, Ehret GB, Ruczinski I, Scharpf RB, Chen YD, de Boer IH, Haritunians T, Lumley T, Sarnak M, Siscovick D, Benjamin EJ, Levy D, Upadhyay A, Aulchenko YS, Hofman A, Rivadeneira F, Uitterlinden AG, van Duijn CM, Chasman DI, Paré G, Ridker PM, Kao WH, Witteman JC, Coresh J, Shlipak MG, Fox CS (2009) Multiple loci associated with indices of renal function and chronic kidney disease. Nat Genet 41(6):712–717PubMedCrossRef
15.
go back to reference Cullen ME, Yuen AH, Felkin LE, Smolenski RT, Hall JL, Grindle S, Miller LW, Birks EJ, Yacoub MH, Barton PJ (2006) Myocardial expression of the arginine:glycine amidinotransferase gene is elevated in heart failure and normalized after recovery: potential implications for local creatine synthesis. Circulation 114(1 Suppl):16–20 Cullen ME, Yuen AH, Felkin LE, Smolenski RT, Hall JL, Grindle S, Miller LW, Birks EJ, Yacoub MH, Barton PJ (2006) Myocardial expression of the arginine:glycine amidinotransferase gene is elevated in heart failure and normalized after recovery: potential implications for local creatine synthesis. Circulation 114(1 Suppl):16–20
16.
go back to reference Dobnig H, Piswanger-Sölkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Sieberer C, Fahrleitner-Pammer A (2006) Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 91(9):3355–63PubMedCrossRef Dobnig H, Piswanger-Sölkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Sieberer C, Fahrleitner-Pammer A (2006) Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 91(9):3355–63PubMedCrossRef
17.
go back to reference Dobnig H, Piswanger-Sölkner JC, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Riedmüller G, Brueck C, Fahrleitner-Pammer A (2007) Hip and nonvertebral fracture prediction in nursing home patients: role of bone ultrasound and bone marker measurements. J Clin Endocrinol Metab 92(5):1678–86PubMedCrossRef Dobnig H, Piswanger-Sölkner JC, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Riedmüller G, Brueck C, Fahrleitner-Pammer A (2007) Hip and nonvertebral fracture prediction in nursing home patients: role of bone ultrasound and bone marker measurements. J Clin Endocrinol Metab 92(5):1678–86PubMedCrossRef
18.
go back to reference Meinitzer A, Puchinger M, Winklhofer-Roob BM, Rock E, Ribalta J, Roob JM, Sundl I, Halwachs-Baumann G, März W (2007) Reference values for plasma concentrations of asymmetrical dimethylarginine (ADMA) and other arginine metabolites in men after validation of a chromatographic method. Clin Chim Acta 384(1–2):141–8PubMedCrossRef Meinitzer A, Puchinger M, Winklhofer-Roob BM, Rock E, Ribalta J, Roob JM, Sundl I, Halwachs-Baumann G, März W (2007) Reference values for plasma concentrations of asymmetrical dimethylarginine (ADMA) and other arginine metabolites in men after validation of a chromatographic method. Clin Chim Acta 384(1–2):141–8PubMedCrossRef
19.
go back to reference Hauk JM, Hosey RG (2006) Nitric oxide therapy: fact or fiction? Curr Sports Med Rep 5(4):199–202PubMed Hauk JM, Hosey RG (2006) Nitric oxide therapy: fact or fiction? Curr Sports Med Rep 5(4):199–202PubMed
20.
go back to reference Rao SLN (2011) A look at the brighter facets of β-N-oxalyl-l-α, β-diaminopropionic acid, homoarginine and the grass pea. Food Chem Toxicol 49(3):620–2PubMedCrossRef Rao SLN (2011) A look at the brighter facets of β-N-oxalyl-l-α, β-diaminopropionic acid, homoarginine and the grass pea. Food Chem Toxicol 49(3):620–2PubMedCrossRef
Metadata
Title
Associations of homoarginine with bone metabolism and density, muscle strength and mortality: cross-sectional and prospective data from 506 female nursing home patients
Authors
S. Pilz
A. Meinitzer
A. Tomaschitz
K. Kienreich
H. Dobnig
M. Schwarz
D. Wagner
C. Drechsler
C. Piswanger-Sölkner
W. März
A. Fahrleitner-Pammer
Publication date
01-01-2013
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 1/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-012-1950-9

Other articles of this Issue 1/2013

Osteoporosis International 1/2013 Go to the issue