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The Association of Aromatic Amino Acids with Incident Hip Fracture, aBMD, and Body Composition from the Cardiovascular Health Study

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Abstract

In 5187 persons from the Cardiovascular Health Study, there was no significant association of dietary intakes of aromatic amino acids (AAA) with areal BMD of the hip or body composition. However, those who had the lowest dietary intakes of AAA were at increased risk for incident hip fractures. Prior studies of the association of protein intake with osteoporosis are conflicting and have not directly examined the relationship of aromatic amino acids (AAA) with fractures, areal bone mineral density (aBMD), and body composition. We sought to determine the relationship of dietary intakes of AAA with osteoporosis parameters in elderly men and women. 5187 men and women aged ≥ 65 years from the Cardiovascular Health Study (CHS) with dietary intakes of AAA (tryptophan, phenylalanine, tyrosine) estimated by food frequency questionnaire (FFQ) were included. We examined the relationship between a one-time estimate of daily dietary AAA intake with risk of incident hip fractures over a median of 13.2 years of fracture follow-up. A subset (n = 1336) who had dual energy X-ray absorptiometry (DXA) performed were included in a cross-sectional analysis of the association of dietary AAA intake with aBMD of the total hip and measurements of body composition. In multivariable models adjusted for demographic and clinical variables, medication use, and diet, higher dietary AAA intake was not significantly associated with incident hip fractures. All hazard ratios (HR) were less than one (tryptophan, HR 0.14, 95% CI 0.01 to 1.89; phenylalanine, HR 0.60, 95% CI 0.23 to 1.55; tyrosine, HR 0.59, 95% CI 0.27 to 1.32), but confidence intervals were wide and included no difference. However, in post hoc analyses, the lowest quartile of intake for each AAA was associated with an increased risk for hip fracture compared to higher quartiles (p ≤ 0.047 for all). Dietary AAA intakes were not significantly associated with total hip aBMD or any measurements of body composition. Overall, there was no significant association of dietary AAA intake with hip fractures, aBMD of the hip, or body composition. However, there may be a subset of elderly individuals with low dietary intakes of AAA who are at increased for hip fractures.

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References

  1. Fiatarone Singh MA (2014) Exercise, nutrition and managing hip fracture in older persons. Curr Opin Clin Nutr Metab Care 17(1):12–24

    CAS  PubMed  Google Scholar 

  2. Surdykowski AK, Kenny AM, Insogna KL, Kerstetter JE (2010) Optimizing bone health in older adults: the importance of dietary protein. Aging Health 6(3):345–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Holmes MD, Pollak MN, Willett WC, Hankinson SE (2002) Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol Biomark Prev 11(9):852–861

    CAS  Google Scholar 

  4. Conigrave AD, Brown EM, Rizzoli R (2008) Dietary protein and bone health: roles of amino acid-sensing receptors in the control of calcium metabolism and bone homeostasis. Annu Rev Nutr 28:131–155

    Article  CAS  PubMed  Google Scholar 

  5. Robinson SM, Reginster JY, Rizzoli R, Shaw SC, Kanis JA, Bautmans I et al (2018) Does nutrition play a role in the prevention and management of sarcopenia? Clin Nutr (Edinburgh, Scotland). 37(4):1121–1132

    Article  CAS  Google Scholar 

  6. Rizzoli R, Biver E, Bonjour JP, Coxam V, Goltzman D, Kanis JA et al (2018) Benefits and safety of dietary protein for bone health-an expert consensus paper endorsed by the European Society for Clinical and Economical Aspects of Osteopororosis, Osteoarthritis, and Musculoskeletal Diseases and by the International Osteoporosis Foundation. Osteoporos Int 29(9):1933–1948

    Article  CAS  PubMed  Google Scholar 

  7. Langsetmo L, Shikany JM, Cawthon PM, Cauley JA, Taylor BC, Vo TN et al (2017) The association between protein intake by source and osteoporotic fracture in older men: a prospective cohort study. J Bone Miner Res 32(3):592–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kim MH, Lee JS, Johnson MA (2015) Poor socioeconomic and nutritional status are associated with osteoporosis in korean postmenopausal women: data from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES) 2009. J Am Coll Nutr 34(5):400–407

    Article  CAS  PubMed  Google Scholar 

  9. Isanejad M, Mursu J, Sirola J, Kroger H, Rikkonen T, Tuppurainen M et al (2015) Association of protein intake with the change of lean mass among elderly women: the Osteoporosis Risk Factor and Prevention - Fracture Prevention Study (OSTPRE-FPS). J Nutr Sci 4:e41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shariati-Bafghi SE, Nosrat-Mirshekarlou E, Karamati M, Rashidkhani B (2014) Higher dietary acidity is associated with lower bone mineral density in postmenopausal iranian women, independent of dietary calcium intake. Int J Vitam Nutr Res 84(3–4):206–217

    Article  CAS  PubMed  Google Scholar 

  11. Thorpe MP, Jacobson EH, Layman DK, He X, Kris-Etherton PM, Evans EM (2008) A diet high in protein, dairy, and calcium attenuates bone loss over twelve months of weight loss and maintenance relative to a conventional high-carbohydrate diet in adults. J Nutr 138(6):1096–1100

    Article  CAS  PubMed  Google Scholar 

  12. Kukuljan S, Nowson CA, Bass SL, Sanders K, Nicholson GC, Seibel MJ et al (2009) Effects of a multi-component exercise program and calcium-vitamin-D3-fortified milk on bone mineral density in older men: a randomised controlled trial. Osteoporos Int 20(7):1241–1251

    Article  CAS  PubMed  Google Scholar 

  13. Sukumar D, Ambia-Sobhan H, Zurfluh R, Schlussel Y, Stahl TJ, Gordon CL et al (2011) Areal and volumetric bone mineral density and geometry at two levels of protein intake during caloric restriction: a randomized, controlled trial. J Bone Miner Res 26(6):1339–1348

    Article  CAS  PubMed  Google Scholar 

  14. Tirosh A, de Souza RJ, Sacks F, Bray GA, Smith SR, LeBoff MS (2015) Sex differences in the effects of weight loss diets on bone mineral density and body composition: POUNDS LOST trial. J Clin Endocrinol Metab 100(6):2463–2471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jesudason D, Nordin BC, Keogh J, Clifton P (2013) Comparison of 2 weight-loss diets of different protein content on bone health: a randomized trial. Am J Clin Nutr 98(5):1343–1352

    Article  CAS  PubMed  Google Scholar 

  16. Kerstetter JE, Bihuniak JD, Brindisi J, Sullivan RR, Mangano KM, Larocque S et al (2015) The effect of a whey protein supplement on bone mass in older caucasian adults. J Clin Endocrinol Metab 100(6):2214–2222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schurch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP (1998) Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 128(10):801–809

    Article  CAS  PubMed  Google Scholar 

  18. Jennings A, MacGregor A, Spector T, Cassidy A (2016) Amino acid intakes are associated with bone mineral density and prevalence of low bone mass in women: evidence from discordant monozygotic twins. J Bone Miner Res 31(2):326–335

    Article  CAS  PubMed  Google Scholar 

  19. Zhao Q, Shen H, Su KJ, Zhang JG, Tian Q, Zhao LJ et al (2018) Metabolomic profiles associated with bone mineral density in US Caucasian women. Nutr Metab 15:57

    Article  CAS  Google Scholar 

  20. You YS, Lin CY, Liang HJ, Lee SH, Tsai KS, Chiou JM et al (2014) Association between the metabolome and low bone mineral density in Taiwanese women determined by (1)H NMR spectroscopy. J Bone Miner Res 29(1):212–222

    Article  CAS  PubMed  Google Scholar 

  21. Refaey ME, Zhong Q, Ding KH, Shi XM, Xu J, Bollag WB et al (2014) Impact of dietary aromatic amino acids on osteoclastic activity. Calcif Tissue Int 95(2):174–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ding KH, Cain M, Davis M, Bergson C, McGee-Lawrence M, Perkins C et al (2018) Amino acids as signaling molecules modulating bone turnover. Bone 115:15–24

    Article  CAS  PubMed  Google Scholar 

  23. Sibilia V, Pagani F, Lattuada N, Greco A, Guidobono F (2009) Linking chronic tryptophan deficiency with impaired bone metabolism and reduced bone accrual in growing rats. J Cell Biochem 107(5):890–898

    Article  CAS  PubMed  Google Scholar 

  24. Conigrave AD, Mun HC, Lok HC (2007) Aromatic L-amino acids activate the calcium-sensing receptor. J Nutr 137(6 Suppl 1):1524S–1527S (discussion 48S)

    Article  CAS  PubMed  Google Scholar 

  25. Michalowska M, Znorko B, Kaminski T, Oksztulska-Kolanek E, Pawlak D (2015) New insights into tryptophan and its metabolites in the regulation of bone metabolism. J Physiol Pharmacol 66(6):779–791

    CAS  PubMed  Google Scholar 

  26. El Refaey M, Watkins CP, Kennedy EJ, Chang A, Zhong Q, Ding KH et al (2015) Oxidation of the aromatic amino acids tryptophan and tyrosine disrupts their anabolic effects on bone marrow mesenchymal stem cells. Mol Cell Endocrinol 410:87–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tessari P, Lante A, Mosca G (2016) Essential amino acids: master regulators of nutrition and environmental footprint? Sci Rep 6:26074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fernstrom JD, Fernstrom MH (2007) Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr 137(6 Suppl 1):1539S-47S (discussion 48S)

    Google Scholar 

  29. Koura HM, Abdallah Ismail N, Kamel AF, Ahmed AM, Saad-Hussein A, Effat LK (2011) A long-term study of bone mineral density in patients with phenylketonuria under diet therapy. Arch Med Sci 7(3):493–500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Carbone LD, Buzkova P, Fink HA, Raiford M, Le B, Isales CM et al (2019) Association of dietary niacin intake with incident hip fracture, BMD, and body composition: the cardiovascular health study. J Bone Miner Res. https://doi.org/10.1002/jbmr.3639

    Article  PubMed  PubMed Central  Google Scholar 

  31. Karsenty G, Yadav VK (2011) Regulation of bone mass by serotonin: molecular biology and therapeutic implications. Annu Rev Med 62:323–331

    Article  CAS  PubMed  Google Scholar 

  32. Fried LP, Borhani NO, Enright P, Furberg CD, Gardin JM, Kronmal RA et al (1991) The cardiovascular health study: design and rationale. Ann Epidemiol 1(3):263–276

    Article  CAS  PubMed  Google Scholar 

  33. Kumanyika S, Tell GS, Fried L, Martel JK, Chinchilli VM (1996) Picture-sort method for administering a food frequency questionnaire to older adults. J Am Diet Assoc 96(2):137–144

    Article  CAS  PubMed  Google Scholar 

  34. Robbins J, Hirsch C, Whitmer R, Cauley J, Harris T (2001) The association of bone mineral density and depression in an older population. J Am Geriatr Soc 49(6):732–736

    Article  CAS  PubMed  Google Scholar 

  35. Mitchell D, Haan MN, Steinberg FM, Visser M (2003) Body composition in the elderly: the influence of nutritional factors and physical activity. J Nutr Health Aging 7(3):130–139

    CAS  PubMed  Google Scholar 

  36. Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R et al (2003) Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26(11):3160–3167

    Article  PubMed  Google Scholar 

  37. Barzilay JI, Blaum C, Moore T, Xue QL, Hirsch CH, Walston JD et al (2007) Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med 167(7):635–641

    Article  PubMed  Google Scholar 

  38. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol Series A 56(3):M146–M156

    Article  CAS  Google Scholar 

  39. Macy EM, Hayes TE, Tracy RP (1997) Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications. Clin Chem 43(1):52–58

    CAS  PubMed  Google Scholar 

  40. Cushman M, Cornell ES, Howard PR, Bovill EG, Tracy RP (1995) Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem 41(2):264–270

    CAS  PubMed  Google Scholar 

  41. Aday LA, Andersen RM (1981) Equity of access to medical care: a conceptual and empirical overview. Med Care 19(12):4–27

    Article  CAS  PubMed  Google Scholar 

  42. Dawson-Hughes B, Harris SS, Rasmussen HM, Dallal GE (2007) Comparative effects of oral aromatic and branched-chain amino acids on urine calcium excretion in humans. Osteoporos Int 18(7):955–961

    Article  CAS  PubMed  Google Scholar 

  43. Pernow Y, Thoren M, Saaf M, Fernholm R, Anderstam B, Hauge EM et al (2010) Associations between amino acids and bone mineral density in men with idiopathic osteoporosis. Bone 47(5):959–965

    Article  CAS  PubMed  Google Scholar 

  44. Pencharz PB, Hsu JW, Ball RO (2007) Aromatic amino acid requirements in healthy human subjects. J Nutr 137(6 Suppl 1):1576S–1578S (discussion 97S-98S)

    Article  CAS  PubMed  Google Scholar 

  45. Iguacel I, Miguel-Berges ML, Gomez-Bruton A, Moreno LA, Julian C (2019) Veganism, vegetarianism, bone mineral density, and fracture risk: a systematic review and meta-analysis. Nutr Rev 77(1):1–18

    Article  PubMed  Google Scholar 

  46. Vidal C, Li W, Santner-Nanan B, Lim CK, Guillemin GJ, Ball HJ et al (2015) The kynurenine pathway of tryptophan degradation is activated during osteoblastogenesis. Stem Cells (Dayton, Ohio) 33(1):111–121

    Article  CAS  Google Scholar 

  47. Refaey ME, McGee-Lawrence ME, Fulzele S, Kennedy EJ, Bollag WB, Elsalanty M et al (2017) Kynurenine, a tryptophan metabolite that accumulates with age, induces bone loss. J Bone Miner Res 32(11):2182–2193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Apalset EM, Gjesdal CG, Ueland PM, Midttun O, Ulvik A, Eide GE et al (2014) Interferon (IFN)-gamma-mediated inflammation and the kynurenine pathway in relation to bone mineral density: the Hordaland Health Study. Clin Exp Immunol 176(3):452–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Apalset EM, Gjesdal CG, Ueland PM, Oyen J, Meyer K, Midttun O et al (2014) Interferon gamma (IFN-gamma)-mediated inflammation and the kynurenine pathway in relation to risk of hip fractures: the Hordaland Health Study. Osteoporos Int 25(8):2067–2075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Drs. Carbone, Bůžková, Fink, Isales, Le, Shikany, Coughlin, and Robbins participated in the analysis/interpretation of the data, drafting and/or critical analysis of the manuscript and approved the final version of the submitted manuscript. Mattie Raiford participated in drafting the manuscript, approved the final version, and assisted with interpretation of the data. Drs. Carbone, Bůžková, and Robbins accept responsibility for the integrity of the data analysis. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and Grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.

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Authors and Affiliations

  1. Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, USA

    Brian Le, Mattie Raiford, Steven S. Coughlin & Laura D. Carbone

  2. Department of Medicine, Medical College of Georgia, Augusta University (formerly Georgia Regents University and Georgia Health Sciences University), Augusta, GA, USA

    Brian Le, Mattie Raiford & Carlos M. Isales

  3. Department of Biostatistics, University of Washington, Seattle, WA, USA

    Petra Bůžková

  4. Department of Medicine, University of California – Davis, Sacramento, CA, USA

    John A. Robbins

  5. Geriatric Research Education & Clinical Center, Veterans Affairs Health Care System, Minneapolis, MN, USA

    Howard A. Fink

  6. Center for Chronic Disease Outcomes Research, Veterans Affairs Health Care System, Minneapolis, MN, USA

    Howard A. Fink

  7. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Howard A. Fink

  8. Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA

    Howard A. Fink

  9. Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    James M. Shikany

  10. Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Steven S. Coughlin

  11. Department of Medicine, J. Harold Harrison MD Distinguished University Chair in Rheumatology, Medical College of Georgia, Augusta University (formerly Georgia Regents University and Georgia Health Sciences University), Augusta, GA, USA

    Laura D. Carbone

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  1. Brian Le
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Correspondence to Laura D. Carbone.

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Brian Le, Petra Bůžková, John Robbins, Howard Fink, Mattie Raiford, Carlos Isales, James Shikany, Steven Coughlin, and Laura Carbone have no conflict of interest.

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The study was approved by the Institutional Review Board (IRB) at each site. All participants gave written informed consent.

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Le, B., Bůžková, P., Robbins, J.A. et al. The Association of Aromatic Amino Acids with Incident Hip Fracture, aBMD, and Body Composition from the Cardiovascular Health Study. Calcif Tissue Int 105, 161–172 (2019). https://doi.org/10.1007/s00223-019-00562-9

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