Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Osteoporosis International
Published in: Osteoporosis International 8/2017

01-08-2017 | Review

The association between serum uric acid level and the risk of fractures: a systematic review and meta-analysis

Authors: P. Yin, H. Lv, Y. Li, Y. Meng, L. Zhang, P. Tang

Published in: Osteoporosis International | Issue 8/2017

Login to get access

Abstract

Controversy has arisen in regarding the association between serum uric acid (UA) and fracture risk. Therefore, we conducted a systemic review and meta-analysis by pooling estimate of five prospective studies (29,110 participants). Results showed that an increased serum UA level is associated with a lower risk of fracture. Numerous studies have demonstrated that high serum UA is a relevant risk factor for a wide variety of diseases, whereas new understanding in serum uric acid follows recent reports demonstrating a protective role of UA in health status. However, the association between serum UA and fracture remains controversial. Therefore, we conduct a systemic review and meta-analysis to determine whether elevated UA level is a protective factor for fracture among prospective studies. We searched for studies published before May 6, 2016, using PubMed, Embase, and Cochrane databases, without any language restriction. The inclusion criteria were published studies investigating the association between UA and fractures. Two authors independently screened the retrieved articles in accordance to the predefined inclusion criteria. We pooled the study-specific relative risk estimates using a random-effect model for comparison of persons whose UA levels were in the top tertile with those in the bottom tertile. Factors that may predict these associations were evaluated in subgroup analysis and meta-regression. The five included prospective studies included 29,110 participants. In random-effect models that included all five included studies, the summary hazard ratios (HRs) (top vs bottom tertiles) were 079 (95% CI, 0.69 to 0.89), without evidence of heterogeneity (P for heterogeneity = 0.458; I 2 = 0%). Similar results were shown when pooling estimate of three higher-quality studies (HR 0.80 95% CI, 0.69 to 0.93). The association between UA and fracture remained in sensitivity and subgroup analyses. An increased serum UA level is shown to be associated with a lower risk of fracture, albeit additional large, high-quality prospective studies or a meta-analysis of individual data are still needed to verify the association.
Appendix
Available only for authorised users
Literature
1.
2.
Kellogg EW, Fridovich I (1977) Liposome oxidation and erythrocyte lysis by enzymically generated superoxide and hydrogen peroxide. J Biol Chem 252(19):6721–6728PubMed
3.
4.
Waring SW, Webb DJ, Maxwell SR (2001) Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol 38(3):365–371CrossRefPubMed
5.
6.
Paganoni S, Zhang M, Quiroz Zarate A, Jaffa M, Yu H, Cudkowicz ME et al (2012) Uric acid levels predict survival in men with amyotrophic lateral sclerosis. J Neurol 259(9):1923–1928CrossRefPubMedPubMedCentral
7.
Holme I, Aastveit 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):558–570CrossRefPubMed
8.
Oda E, Kawai R, Sukumaran V, Watanabe K (2009) Uric acid is positively associated with metabolic syndrome but negatively associated with diabetes in Japanese men. Internal medicine (Tokyo, Japan) 48(20):1785–1791CrossRef
9.
Ames BN, Cathcart R, Schwiers E, Hochstein P (1981) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A 78(11):6858–6862CrossRefPubMedPubMedCentral
10.
Sautin YY, Johnson RJ (2008) Uric acid: the oxidant-antioxidant paradox. Nucleosides, nucleotides & nucleic acids 27(6):608–619CrossRef
11.
Landmesser U, Spiekermann S, Dikalov S, Tatge H, Wilke R, Kohler C et al (2002) Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine-oxidase and extracellular superoxide dismutase. Circulation 106(24):3073–3078CrossRefPubMed
12.
13.
Sanchez-Rodriguez MA, Ruiz-Ramos M, Correa-Munoz E, Mendoza-Nunez VM (2007) Oxidative stress as a risk factor for osteoporosis in elderly Mexicans as characterized by antioxidant enzymes. BMC Musculoskelet Disord 8:124CrossRefPubMedPubMedCentral
14.
Basu S, Michaelsson K, Olofsson H, Johansson S, Melhus H (2001) Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun 288(1):275–279CrossRefPubMed
15.
Mody N, Parhami F, Sarafian TA, Demer LL (2001) Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 31(4):509–519CrossRefPubMed
16.
Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y (2009) Oxidative stress in bone remodelling and disease. Trends Mol Med 15(10):468–477CrossRefPubMed
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. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 30(6):992–999CrossRef
18.
Ahn SH, Lee SH, Kim BJ, Lim KH, Bae SJ, Kim EH et al (2013) Higher serum uric acid is associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in healthy postmenopausal women. Osteoporosis international. a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 24(12):2961–2970CrossRef
19.
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. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 26(5):955–964CrossRef
20.
Lane NE, Parimi N, Lui LY, Wise BL, Yao W, Lay YA et al (2014) Association of serum uric acid and incident nonspine fractures in elderly men: the Osteoporotic Fractures in Men (MrOS) study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 29(7):1701–1707CrossRef
21.
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. Osteoporosis international. a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 25(7):1837–1844CrossRef
22.
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):1113–1122CrossRefPubMed
23.
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. Metab Clin Exp 64(3):438–446CrossRefPubMed
24.
Veronese N, Bolzetta F, De Rui M, Maggi S, Noale M, Zambon S et al (2015) Serum uric acid and incident osteoporotic fractures in old people: the PRO.V.A study. Bone 79:183–189CrossRefPubMed
25.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012CrossRefPubMed
26.
Rodondi N, Aujesky D, Vittinghoff E, Cornuz J, Bauer DC (2006) Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis. Am J Med 119(7):541–551CrossRefPubMed
27.
Egger M, Smith GD, Schneider M (2008) Systematic reviews of observational studies. Systematic reviews in health care. BMJ Publishing Group:211–227
28.
Wirth CD, Blum MR, da Costa BR, Baumgartner C, Collet TH, Medici M et al (2014) Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis. Ann Intern Med 161(3):189–199CrossRefPubMedPubMedCentral
29.
Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC et al (2014) Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ (Clinical research ed) 348:g1903
30.
Danesh J, Collins R, Appleby P, Peto R (1998) Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 279(18):1477–1482CrossRefPubMed
31.
Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L et al (2014) Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med 160(6):398–406CrossRefPubMed
32.
33.
Lee JS, Buzkova P, Fink HA, Vu J, Carbone L, Chen Z et al (2010) Subclinical thyroid dysfunction and incident hip fracture in older adults. Arch Intern Med 170(21):1876–1883CrossRefPubMedPubMedCentral
34.
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558CrossRefPubMed
35.
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 315(7109):629–634CrossRef
36.
Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101CrossRefPubMed
37.
Makovey J, Macara M, Chen JS, Hayward CS, March L, Seibel MJ et al (2013) Serum uric acid plays a protective role for bone loss in peri- and postmenopausal women: a longitudinal study. Bone 52(1):400–406CrossRefPubMed
38.
Dalbeth N, Gamble GD, Horne A, Reid IR (2016) Relationship between changes in serum urate and bone mineral density during treatment with thiazide diuretics: secondary analysis from a randomized controlled trial. Calcif Tissue Int 98(5):474–478CrossRefPubMed
39.
Xiong A, Yao Q, He J, Fu W, Yu J, Zhang Z (2016) No causal effect of serum urate on bone-related outcomes among a population of postmenopausal women and elderly men of Chinese Han ethnicity-a Mendelian randomization study. Osteoporosis international. a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 27(3):1031–1039CrossRef
40.
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(5):e0154692CrossRefPubMedPubMedCentral
41.
Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA (2005) Uric acid and oxidative stress. Curr Pharm Des 11(32):4145–4151CrossRefPubMed
42.
Waring WS, Webb DJ, Maxwell SR (2001) Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol 38(3):365–371CrossRefPubMed
43.
Almeida M, Han L, Martin-Millan M, O’Brien CA, Manolagas SC (2007) Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J Biol Chem 282(37):27298–27305CrossRefPubMed
44.
Ostman B, Michaelsson K, Helmersson J, Byberg L, Gedeborg R, Melhus H et al (2009) Oxidative stress and bone mineral density in elderly men: antioxidant activity of alpha-tocopherol. Free Radic Biol Med 47(5):668–673CrossRefPubMed
45.
Gao X, O’Reilly EJ, Schwarzschild MA, Ascherio A (2016) Prospective study of plasma urate and risk of Parkinson disease in men and women. Neurology 86(6):520–526CrossRefPubMedPubMedCentral
46.
Chen H, Mosley TH, Alonso A, Huang X (2009) Plasma urate and Parkinson’s disease in the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol 169(9):1064–1069CrossRefPubMedPubMedCentral
47.
Khanna D, Khanna PP, Fitzgerald JD, Singh MK, Bae S, Neogi T et al (2012) 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis care & research 64(10):1447–1461CrossRef
48.
Lems WF (2015) Fracture risk estimation may facilitate the treatment gap in osteoporosis. Ann Rheum Dis 74(11):1943–1945CrossRefPubMed
49.
Altman DG (2001) Systematic reviews of evaluations of prognostic variables. BMJ (Clinical research ed) 323(7306):224–228CrossRef
50.
Sterne JA, Egger M, Smith GD (2001) Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ (Clinical research ed) 323(7304):101–105CrossRef
Metadata
Title
The association between serum uric acid level and the risk of fractures: a systematic review and meta-analysis
Authors
P. Yin
H. Lv
Y. Li
Y. Meng
L. Zhang
P. Tang
Publication date
01-08-2017
Publisher
Springer London
Published in
Osteoporosis International / Issue 8/2017
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-017-4059-3

Other articles of this Issue 8/2017

Osteoporosis International 8/2017 Go to the issue

Original Article

Examining the treatment gap and risk of subsequent fractures among females with a fragility fracture in the US Medicare population

Review

Spinal radiographs in those with back pain—when are they appropriate to diagnose vertebral fractures?

Original Article

Sex-related variations in cortical and trabecular bone of the femoral neck in an elderly Chinese population

Original Article

Dietary acid load, trabecular bone integrity, and mineral density in an ageing population: the Rotterdam study

Original Article

A multicenter retrospective study of the risk factors associated with medication-related osteonecrosis of the jaw after tooth extraction in patients receiving oral bisphosphonate therapy: can primary wound closure and a drug holiday really prevent MRONJ?

Original Article

The role of adipokines as prognostic factors of one-year mortality in hip fracture patients