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Association between serum uric acid and bone health in adolescents

  • F. Karimi
  • M. H. Dabbaghmanesh
  • G. R. OmraniEmail author
Original Article
  • 57 Downloads

Abstract

Summary

Previous studies are suggestive of the protective role of uric acid on bone in the middle-aged and elderly. Whether this association exists in younger individuals has not been examined. This investigation showed a significant positive association between serum uric acid and bone parameters among Iranian adolescents.

Introduction

Uric acid (UA) might be linked to bone health, but it is unclear whether its effects on bone are limited to certain population subgroups. This study is aimed at investigating the correlation between serum uric acid levels and bone mineral density (BMD) in Iranian adolescents.

Methods

This cross-sectional study was conducted on 413 (221 girls and 192 boys) Iranian adolescents aged 9–19 years. An analysis of anthropometric, biochemical parameters and bone density was performed on the participants. Measurements included serum uric acid, calcium, phosphorus, alkaline phosphatase, albumin, and vitamin D. They were divided according to their serum UA into the low UA group who had UA ≤ 6 mg/dL and the high UA group with UA > 6 mg/dL. BMD and bone mineral content (BMC) were measured in the total body, lumbar spine, and left femoral neck, using dual energy X-ray absorptiometry (DXA), and bone mineral apparent density (BMAD) was calculated.

Results

A Pearson correlation analysis revealed a significant correlation between UA and bone parameters. In multiple regression analyses adjusted for potential confounders, serum UA was proven to be associated with BMD and BMC at all sites. There was no association between UA, serum calcium, and vitamin D concentrations.

Conclusion

Our study, as the first research on adolescents, demonstrated a higher bone density in those who had higher UA levels.

Keywords

Adolescent Bone mineral apparent density Bone mineral content Bone mineral density Uric acid 

Notes

Acknowledgments

The authors would like to thank all the colleagues working on the project, especially the staff of the Endocrinology and Metabolism Research Center of Shiraz University of Medical Sciences, for their cooperation. The authors also wish to thank Mr. H. Argasi at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his assistance in editing this manuscript.

Funding

This work was financially supported by the research Vice Chancellor of Shiraz University of Medical Sciences (grant number 9591).

Compliance with ethical standards

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflicts of interest

None.

References

  1. 1.
    Michael AL (2012) Assessing bone health in children and adolescents. Indian J Endocrinol Metab 16(Suppl 2):S205–S212.  https://doi.org/10.4103/2230-8210.104040 Google Scholar
  2. 2.
    Ashouri E, Meimandi EM, Saki F, Dabbaghmanesh MH, Omrani GR, Bakhshayeshkaram M (2015) The impact of LRP5 polymorphism (rs556442) on calcium homeostasis, bone mineral density, and body composition in Iranian children. J Bone Miner Metab 33(6):651–657.  https://doi.org/10.1007/s00774-014-0624-4 CrossRefGoogle Scholar
  3. 3.
    Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM et al (2004) Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 314:197–207CrossRefGoogle Scholar
  4. 4.
    Lee YJ, Hong JY, Kim SC, Joo JK, Na YJ, Lee KS (2015) The association between oxidative stress and bone mineral density according to menopausal status of Korean women. Obstet Gynecol Sci 58(1):46–52.  https://doi.org/10.5468/ogs.2015.58.1.46 CrossRefGoogle Scholar
  5. 5.
    Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL (2009) Inverse association of carotenoid intakes with 4-y change in bone mineral density in elderly men and women: the Framingham Osteoporosis Study. Am J Clin Nutr 89(1):416–424.  https://doi.org/10.3945/ajcn.2008.26388 CrossRefGoogle Scholar
  6. 6.
    Nabipour I, Sambrook PN, Blyth FM, Janu MR, Waite LM, Naganathan V et al (2011) Serum uric acid is associated with bone health in older men: a cross-sectional population-based study. J Bone Miner Res Off J Am Soc Bone Miner Res 26(5):955–964.  https://doi.org/10.1002/jbmr.286 CrossRefGoogle Scholar
  7. 7.
    Ishii S, Miyao M, Mizuno Y, Tanaka-Ishikawa M, Akishita M, Ouchi Y (2014) Association between serum uric acid and lumbar spine bone mineral density in peri- and postmenopausal Japanese women. Osteoporos Int 25(3):1099–1105.  https://doi.org/10.1007/s00198-013-2571-7 CrossRefGoogle Scholar
  8. 8.
    Kim BJ, Baek S, Ahn SH, Kim SH, Jo MW, Bae SJ et al (2014) Higher serum uric acid as a protective factor against incident osteoporotic fractures in Korean men: a longitudinal study using the National Claim Registry. Osteoporos Int 25(7):1837–1844.  https://doi.org/10.1007/s00198-014-2697-2 CrossRefGoogle Scholar
  9. 9.
    Chen W, Roncal-Jimenez C, Lanaspa M, Gerard S, Chonchol M, Johnson RJ et al (2014) Uric acid suppresses 1 alpha hydroxylase in vitro and in vivo. Metabolism 63:150–160.  https://doi.org/10.1016/j.metabol.2013.09.018 CrossRefGoogle Scholar
  10. 10.
    Jeddi M, Roosta MJ, Dabbaghmanesh MH, Ranjbar Omrani G, Ayatollahi SM, Bagheri Z et al (2013) Normative data and percentile curves of bone mineral density in healthy Iranian children aged 9–18 years. Arch Osteoporosis 8:114.  https://doi.org/10.1007/s11657-012-0114-z CrossRefGoogle Scholar
  11. 11.
    Jeddi M, Dabbaghmanesh MH, Ranjbar Omrani G, Ayatollahi SM, Bagheri Z, Bakhshayeshkaram M (2014) Body composition reference percentiles of healthy Iranian children and adolescents in southern Iran. Arch Iran Med 17(10):661–669Google Scholar
  12. 12.
    Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320(7244):1240–1243CrossRefGoogle Scholar
  13. 13.
    Kohrt WM, Bloomfield SA, Little KD, Nelson ME, Yingling VR, American College of Sports M (2004) American College of Sports Medicine Position Stand: physical activity and bone health. Med Sci Sports Exerc 36(11):1985–1996CrossRefGoogle Scholar
  14. 14.
    Carter DR, Bouxsein ML, Marcus R (1992) New approaches for interpreting projected bone densitometry data. J Bone Miner Res 7(2):137–145.  https://doi.org/10.1002/jbmr.5650070204 CrossRefGoogle Scholar
  15. 15.
    Holme I, Aasteveit AH, Hammar N, Jungner I, Walldius G (2009) Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417,734 men and women in the Apolipoprotein Mortality RISk study (AMORIS). J Intern Med 266(6):558–570.  https://doi.org/10.1111/j.1365-2796.2009.02133.x CrossRefGoogle Scholar
  16. 16.
    Mehta T, Buzkova P, Sarnak MJ, Chonchol M, Cauley JA, Wallace E et al (2015) Serum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study. Metabolism 64(3):438–446.  https://doi.org/10.1016/j.metabol.2014.11.006 CrossRefGoogle Scholar
  17. 17.
    Zhang D, Bobulescu IA, Maalouf NM, Adams-Huet B, Poindexter J, Park S et al (2015) Relationship between serum uric acid and bone mineral density in the general population and in rats with experimental hyperuricemia. J Bone Miner Res 30(6):992–999.  https://doi.org/10.1002/jbmr.2430 CrossRefGoogle Scholar
  18. 18.
    Dong XW, Tian HY, He J, Wang C, Qiu R, Chen YM (2016) Elevated serum uric acid is associated with greater bone mineral density and skeletal muscle mass in middle-aged and older adults. PLoS One. 11(15):e0154692.  https://doi.org/10.1371/journal.pone.0154692 CrossRefGoogle Scholar
  19. 19.
    Takir M, Solak Y, Erek A, Köstek O, Oral A, ElçiOğlu ÖC et al (2016) Association between elevated serum uric acid and vitamin D insufficiency among the middle-aged and elderly population. Turk Neph Dial Transpl 25(2):182–186CrossRefGoogle Scholar
  20. 20.
    Chen L, Peng Y, Fang F, Chen J, Pan L, You L (2015) Correlation of serum uric acid with bone mineral density and fragility fracture in patients with primary osteoporosis: a single-center retrospective study of 253 cases. Int J Clin Exp Med 8(4):6291–6294Google Scholar
  21. 21.
    Thakkinstian A, Anothaisintawee T, Chailurkit L, Ratanachaiwong W, Yamwong S, Sritara P et al (2015) Potential causal associations between vitamin D and uric acid: bidirectional mediation analysis. Sci Rep 5:14528.  https://doi.org/10.1038/srep14528 CrossRefGoogle Scholar
  22. 22.
    Hsu CH, Patel SR, Young EW, Vanholder R (1991) Effects of purine derivatives on calcitriol metabolism in rats. Am J Physiol 260:F596–F601.  https://doi.org/10.1152/ajprenal.1991.260.4.F596 Google Scholar
  23. 23.
    Adams JS, Hewison M (2010) Update in vitamin D. J Clin Endocrinol Metab 95(2):471–478.  https://doi.org/10.1210/jc.2009-1773 CrossRefGoogle Scholar
  24. 24.
    Le Couteur DG, Everitt A, Lebel M (2009) The aging liver. Geriatr Aging 12:319–322Google Scholar
  25. 25.
    Paik JM, Farwell WR, Taylor EN (2012) Demographic, dietary, and serum factors and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int. 23(6):1727–1736.  https://doi.org/10.1007/s00198-011-1776-x CrossRefGoogle Scholar
  26. 26.
    So A, Thorens B (2010) Uric acid transport and disease. J Clin Invest 120(6):1791–1799.  https://doi.org/10.1172/JCI42344 CrossRefGoogle Scholar
  27. 27.
    Laspa E, Bastepe M, Ju¨ppner H, Tsatsoulis A (2004) Phenotypic and molecular genetic aspects of pseudohypoparathyroidism type Ib in a Greek kindred: evidence for enhanced uric acid excretion due to parathyroid hormone resistance. J Clin Endocrinol Metab 89(12):5942–5947.  https://doi.org/10.1210/jc.2004-0249 CrossRefGoogle Scholar
  28. 28.
    Miller PD, Schwartz EN, Chen P, Misurski DA, Krege JH (2007) Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment. Osteoporos Int 18(1):59–68.  https://doi.org/10.1007/s00198-006-0189-8 CrossRefGoogle Scholar
  29. 29.
    Ishay A, Herer P, Luboshitzky R (2011) Effects of successful parathyroidectomy on metabolic cardiovascular risk factors in patients with severe primary hyperparathyroidism. Endocr Pract 17:584–590.  https://doi.org/10.4158/EP10321.OR CrossRefGoogle Scholar
  30. 30.
    Kawata T, Imanishi Y, Kobayashi K, Miki T, Arnold A, Inaba M et al (2007) Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. J Am Soc Nephrol 18:2683–2688.  https://doi.org/10.1681/ASN.2006070783 CrossRefGoogle Scholar
  31. 31.
    Bacchetta J, Cochat P, Salusky IB, Wesseling-Perry K (2012) Uric acid and IGF1 as possible determinants of FGF23 metabolism in children with normal renal function. Pediatr Nephrol 27(7):1131–1138.  https://doi.org/10.1007/s00467-012-2110-3 CrossRefGoogle Scholar
  32. 32.
    Gutierrez OM, Wolf M, Taylor EN (2011) Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study. Clin J Am Soc Nephro 16:2871–2878.  https://doi.org/10.2215/CJN.02740311 CrossRefGoogle Scholar
  33. 33.
    Valdemarsson S, Lindblom P, Bergenfelz A (1998) Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment. J Intern Med 244:241–249.  https://doi.org/10.1046/j.1365-2796.1998.00366.x CrossRefGoogle Scholar
  34. 34.
    Ishizaka N, Ishizaka Y, Toda A, Tani M, Koike K, Yamakado M et al (2010) Changes in waist circumference and body mass index in relation to changes in serum uric acid in Japanese individuals. J Rheumatol 37(2):410–416.  https://doi.org/10.3899/jrheum.09073 CrossRefGoogle Scholar
  35. 35.
    Wang H, Wang L, Xie R, Dai W, Gao C, Shen P et al (2014) Association of serum uric acid with body mass index: a cross sectional study from Jiangsu Province, China. Iranian J Publ Health 43(11):1503–1509Google Scholar
  36. 36.
    Miranda JA, Almeida GG, Martins RIL, Cunha MB, Belo VA, Santos JET et al (2015) The role of uric acid in the insulin resistance in children and adolescents with obesity. Rev Paul Pediatr 33(4):431–436.  https://doi.org/10.1016/j.rppede.2015.08.005 CrossRefGoogle Scholar
  37. 37.
    Tsushima Y, Nishizawa H, Tochino Y, Nakatsuji H, Sekimoto R, Nagao H et al (2013) Uric acid secretion from adipose tissue and its increase in obesity. J Biol Chem 288(38):27138–27149.  https://doi.org/10.1074/M113.485094
  38. 38.
    Cheung KJ, Tzameli I, Pissios P, Rovira I, Gavrilova O, Ohtsubo T et al (2007) Xanthine oxidoreductase is a regulator of adipogenesis and PPARγ activity. Cell Metab 5:115–128.  https://doi.org/10.1016/j.cmet.2007.01.005 CrossRefGoogle Scholar
  39. 39.
    Tamba S, Nishizawa H, Funahashi T, Okauchi Y, Ogawa T, Noguchi M et al (2008) Relationship between the serum uric acid level, visceral fat accumulation and serum adiponectin concentration in Japanese men. Intern. Med 47:1175–1180.  https://doi.org/10.2169/internalmedicine.47.0603 CrossRefGoogle Scholar
  40. 40.
    Yamashita S, Matsuzawa Y, Tokunaga K, Fujioka S, Tarui S (1986) Studies on the impaired metabolism of uric acid in obese subjects. Marked reduction of renal urate excretion and its improvement by a low-calorie diet. Int J Obes 10:255–264Google Scholar
  41. 41.
    Cervellati C, Bonaccorsi G, Cremonini E, Romani A, Fila E, Castaldini MC et al (2014) Oxidative stress and bone resorption interplay as a possible trigger for postmenopausal osteoporosis. Biomed Res Int 2014:569563.  https://doi.org/10.1155/2014/569563 Google Scholar
  42. 42.
    Muka T, de Jonge EA, de Jong JC, Uitterlinden AG, Hofman A, Dehghan A et al (2016) The influence of serum uric acid on bone mineral density, hip geometry, and fracture risk: the Rotterdam Study. J Clin Endocrinol Metab 101(3):1113–1122.  https://doi.org/10.1210/jc.2015-2446 CrossRefGoogle Scholar
  43. 43.
    Cauley JA, Fullman RL, Stone KL, Zemuda JM, Bauer DC, Connor EB et al (2005) Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int 16:1525–1537.  https://doi.org/10.1007/soo198-005-1866-8 CrossRefGoogle Scholar
  44. 44.
    Nath SD, Voruganti VS, Arar NH, Thameem F, Lopez-Alvarenga JC, Bauer R et al (2007) Genome scan for determinants of serum uric acid variability. J Am Soc Nephrol 18(12):3156–3163.  https://doi.org/10.1681/ASN.2007040426 CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  1. 1.Endocrinology and Metabolism Research CenterShiraz University of Medical SciencesShirazIran

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