title: C-reactive protein and risk of fracture: a systematic review and dose-response meta-analysis of prospective cohort studies.
abstract: This study systematically reviews prospective cohort studies evaluating the relationship between C-reactive protein (CRP) concentrations and subsequent fracture risk. The positive association cannot completely explain the existing evidence, and further studies are needed to demonstrate the shape of the association.
  
  
  BACKGROUND
  We aimed to perform a systematic review and dose-response meta-analysis of published prospective studies evaluating associations of high-sensitivity CRP (hs-CRP) levels with fracture risk in general populations.
  
  
  METHODS
  We identified relevant studies by searching MEDLINE and EMBASE databases from their inception to May 20, 2014. We included published prospective studies evaluating the associations of hs-CRP levels with risk of fracture in general populations. Two reviewers working independently abstracted the data.
  
  
  RESULTS
  Eight prospective cohort studies involving 34,840 participants and 3,407 incident fracture events were eligible for the present analyses. A meta-analysis of six prospective studies showed that the overall risk for incident fracture in a comparison of individuals in the top tertile with those in the bottom tertile of baseline hs-CRP levels was 2.14 [95% confidence interval (CI) 1.51-3.05, I(2) = 62.3%]. The moderate heterogeneous disappeared when one study was excluded. However, the remaining two studies reported inconsistent results. One study with the biggest sample size showed a U-shaped association for CRP and fracture risk (the association was positive when CRP > 1 mg/L). Similarly, another study reported that per doubling of CRP was positive only when CRP > 3 mg/L.
  
  
  CONCLUSIONS
  In summary, the present analysis showed that the relationship between CRP concentrations and subsequent fracture risk is still inconsistent. The positive association cannot completely explain the existing evidence, and further larger prospective cohorts with more power are needed to demonstrate the shape of the association, especially for the relatively low CRP concentrations, such as less than 3 mg/L.
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, He Di Rd. #71, Nanning, 530021, People's Republic of China.
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Wu
authors.forename: J-L
authors.initials: JL
authors.lastname: He
authors.forename: R-Q
authors.initials: RQ
authors.lastname: Wei
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.forename: J
authors.initials: J
authors.lastname: Guan
authors.forename: Y-B
authors.initials: YB
authors.lastname: Lan
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D058866:Osteoporotic Fractures / Q000097:blood* / Q000453:epidemiology; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods
chemical_list: D018836:Inflammation Mediators; D002097:C-Reactive Protein
references.citation: Rheumatology (Oxford). 2000 Jan;39(1):85-9
references.pmid: 10662879
references.citation: Health Technol Assess. 2010 Feb;14(9):1-151, iii-iv
references.pmid: 20184812
references.citation: BMJ. 2012 Feb 03;344:e454
references.pmid: 22306478
references.citation: Immunol Rev. 2005 Dec;208:228-51
references.pmid: 16313352
references.citation: J Natl Med Assoc. 2005 Mar;97(3):329-33
references.pmid: 15779496
references.citation: Eur J Epidemiol. 2010 Sep;25(9):603-5
references.pmid: 20652370
references.citation: J Clin Endocrinol Metab. 2008 May;93(5):1952-8
references.pmid: 18285417
references.citation: JAMA. 1998 May 13;279(18):1477-82
references.pmid: 9600484
references.citation: JAMA. 2006 Sep 20;296(11):1353-5
references.pmid: 16985226
references.citation: Arthritis Rheum. 2012 Aug;64(8):2624-31
references.pmid: 22487938
references.citation: J Bone Miner Res. 2013 Jul;28(7):1688-98
references.pmid: 23456822
references.citation: Ann Intern Med. 2000 Nov 21;133(10):795-9
references.pmid: 11085842
references.citation: PLoS Med. 2006 Apr;3(4):e90
references.pmid: 16475872
references.citation: Osteoporos Int. 2005 Oct;16(10):1263-71
references.pmid: 15702263
references.citation: J Bone Miner Res. 2014 Feb;29(2):418-23
references.pmid: 23857741
references.citation: Arch Intern Med. 2006 Dec 11-25;166(22):2495-501
references.pmid: 17159016
references.citation: Clin Rheumatol. 2012 Nov;31(11):1529-35
references.pmid: 22706444
references.citation: Bone. 2013 Sep;56(1):67-72
references.pmid: 23702388
references.citation: BMJ. 1997 Sep 13;315(7109):629-34
references.pmid: 9310563
references.citation: Arq Bras Endocrinol Metabol. 2010 Mar;54(2):123-32
references.pmid: 20485900
references.citation: Nat Clin Pract Rheumatol. 2006 Oct;2(10):562-9
references.pmid: 17016482
references.citation: Am J Epidemiol. 1992 Jun 1;135(11):1301-9
references.pmid: 1626547
references.citation: J Clin Epidemiol. 2009 Oct;62(10):e1-34
references.pmid: 19631507
references.citation: Stat Med. 2002 Jun 30;21(12):1803; author reply 1804
references.pmid: 12111913
references.citation: JAMA. 2000 Apr 19;283(15):2008-12
references.pmid: 10789670
references.citation: Osteoporos Int. 2012 Jun;23(6):1683-90
references.pmid: 21927925
references.citation: Calcif Tissue Int. 2012 Jun;90(6):496-506
references.pmid: 22527204
references.citation: J Bone Miner Res. 1993 Oct;8(10):1211-7
references.pmid: 8256658
references.citation: Arch Intern Med. 2004 Feb 23;164(4):420-5
references.pmid: 14980993
references.citation: J Bone Miner Res. 2007 Jul;22(7):1088-95
references.pmid: 17419681
references.citation: Osteoporos Int. 2011 Jul;22(7):2145-50
references.pmid: 20936400
references.citation: Clin Endocrinol (Oxf). 2007 Jul;67(1):152-8
references.pmid: 17466002
references.citation: Osteoporos Int. 2000 Sep;11(8):714-20
references.pmid: 27517712
references.citation: Gastroenterology. 2003 Dec;125(6):1591-7
references.pmid: 14724810
references.citation: Ther Adv Musculoskelet Dis. 2012 Aug;4(4):245-7
references.pmid: 22859923
references.citation: Endocr Rev. 2008 Jun;29(4):441-64
references.pmid: 18451258
references.citation: Osteoporos Int. 2014 Apr;25(4):1247-54
references.pmid: 24337661
references.citation: BMC Musculoskelet Disord. 2012 Jul 23;13:125
references.pmid: 22824097
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120