(Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk; a systematic review of the association between cardiovascular disease and osteoporosis.
BACKGROUND
Both cardiovascular disease and osteoporosis are important causes of morbidity and mortality in the elderly. The co-occurrence of cardiovascular disease and osteoporosis prompted us to review the evidence of an association between cardiovascular (CV) disease and osteoporosis and potential shared common pathophysiological mechanisms.


METHODS
A systematic literature search (Medline, Pubmed and Embase) was conducted to identify all clinical studies that investigated the association between cardiovascular disease and osteoporosis. Relevant studies were screened for quality according to guidelines as proposed by the Dutch Cochrane Centre and evidence was summarized.


RESULTS
Seventy studies were included in this review. Due to a large heterogeneity in study population, design and outcome measures a formal meta-analysis was not possible. Six of the highest ranked studies (mean n = 2,000) showed that individuals with prevalent subclinical CV disease had higher risk for increased bone loss and fractures during follow-up compared to persons without CV disease (range of reported risk: hazard ratio (HR) 1.5; odds ratio (OR) 2.3 to 3.0). The largest study (n = 31,936) reported a more than four times higher risk in women and more than six times higher risk in men. There is moderate evidence that individuals with low bone mass had higher CV mortality rates and incident CV events than subjects with normal bone mass (risk rates 1.2 to 1.4). Although the shared common pathophysiological mechanisms are not fully elucidated, the most important factors that might explain this association appear to be, besides age, estrogen deficiency and inflammation.


CONCLUSIONS
The current evidence indicates that individuals with prevalent subclinical CV disease are at increased risk for bone loss and subsequent fractures. Presently no firm conclusions can be drawn as to what extent low bone mineral density might be associated with increased cardiovascular risk.
Department of Rheumatology, VU Medical Centre, De Boelelaan 1117, 1081 NV Amsterdam, The Netherlands.
Debby
D
den Uyl
Mike T
MT
Nurmohamed
Lilian Hd
LH
van Tuyl
Hennie G
HG
Raterman
Willem F
WF
Lems
D015519:Bone Density; D002318:Cardiovascular Diseases / Q000150:complications* / Q000453:epidemiology; D005260:Female; D050723:Fractures, Bone / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000150:complications* / Q000453:epidemiology; D012307:Risk Factors
Circulation. 1999 Nov 23;100(21):2168-76
10571976
Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E125-32
15367398
Ann Intern Med. 2002 Sep 17;137(6):529-41
12230356
Circulation. 2009 May 5;119(17):2305-12
19380619
Circulation. 2000 Oct 24;102(17):2087-93
11044425
Nature. 2003 May 15;423(6937):337-42
12748652
Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9445-9
12082181
Cerebrovasc Dis. 2007;24(5):418-25
17878722
J Clin Endocrinol Metab. 2003 Mar;88(3):1024-8
12629080
Stroke. 2003 May;34(5):e20-2
12663880
Am J Cardiol. 2008 Apr 15;101(8):1103-4
18394441
Arch Intern Med. 2008 Jun 9;168(11):1174-80
18541825
Ann N Y Acad Sci. 2007 Nov;1117:40-50
18056036
Am J Epidemiol. 2007 Nov 15;166(10):1191-7
17709329
Biochem Biophys Res Commun. 1998 Sep 29;250(3):776-81
9784422
Genes Dev. 1998 May 1;12(9):1260-8
9573043
Cell. 1997 Apr 18;89(2):309-19
9108485
Circ Res. 2004 Oct 15;95(8):773-9
15388638
Circ Cardiovasc Genet. 2010 Feb;3(1):15-21
20160191
Circ J. 2007 Jul;71(7):1095-8
17587717
Immunology. 2001 Jul;103(3):255-61
11454054
J Bone Miner Metab. 2009;27(1):89-94
19057840
J Biol Chem. 2000 Jul 14;275(28):20959-62
10811631
Calcif Tissue Int. 1998 Mar;62(3):209-13
9501953
Eur Heart J. 2001 Dec;22(24):2243-52
11728144
Eur J Endocrinol. 2001 Mar;144(3):257-61
11248745
Calcif Tissue Int. 2007 Oct;81(4):333
17876493
Am J Cardiol. 2005 Oct 15;96(8):1059-63
16214438
J Bone Miner Metab. 2006;24(2):125-31
16502119
Biochem Biophys Res Commun. 2002 Apr 26;293(1):13-7
12054556
Osteoporos Int. 2005 Dec;16(12):1933-8
16079958
J Biol Chem. 2000 Jun 30;275(26):20197-203
10766759
Osteoporos Int. 2005 Dec;16(12):2053-62
16249840
Calcif Tissue Int. 2001 May;68(5):271-6
11683533
Ann Epidemiol. 2007 Nov;17(11):841-6
17728148
Am J Cardiol. 1995 Feb 23;75(6):88B-91B
7863982
Osteoporos Int. 2007 Mar;18(3):251-9
17151836
J Clin Invest. 2000 Nov;106(10):1203-4
11086020
Biochem Biophys Res Commun. 2004 Jul 23;320(2):424-7
15219845
Bone. 2004 Mar;34(3):557-61
15003803
Biochem Biophys Res Commun. 2009 Jul 10;384(4):501-5
19426706
J Bone Miner Res. 1996 Dec;11(12):1841-9
8970884
Am J Cardiol. 2004 Jul 15;94(2):266-9
15246921
Bone Miner. 1992 Nov;19(2):185-94
1422314
Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1161-70
15155384
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):387-92
15225806
J Bone Miner Res. 2007 Sep;22(9):1449-54
17542685
Am J Epidemiol. 2004 Mar 15;159(6):589-95
15003963
Am J Med. 2003 Aug 15;115(3):196-202
12935826
Arch Gerontol Geriatr. 2006 Sep-Oct;43(2):285-8
16426688
Osteoporos Int. 2009 Feb;20(2):257-64
18512114
Osteoporos Int. 2009 Jan;20(1):53-60
18496639
Osteoporos Int. 2008 Aug;19(8):1161-6
18180973
Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2589-96
17932314
J Bone Joint Surg Am. 1966 Sep;48(6):1138-44
5917700
Circulation. 1998 Sep 29;98(13):1302-6
9751679
Circulation. 2007 Jan 30;115(4):459-67
17242284
Int J Cardiol. 2008 Dec 17;131(1):66-9
18222554
Osteoporos Int. 2008 Jan;19(1):49-56
17676381
Metabolism. 2008 Mar;57(3):321-5
18249202
Osteoporos Int. 2007 Jul;18(7):999-1008
17285350
Maturitas. 2006 Oct 20;55(3):212-8
16621356
Jpn J Pharmacol. 1993 Apr;61(4):283-9
8320874
Hypertens Res. 2009 Dec;32(12):1060-6
19816504
Osteoporos Int. 2005 Jan;16(1):64-70
15167987
J Bone Miner Res. 2008 Jan;23(1):95-102
17892380
Calcif Tissue Int. 2006 Oct;79(4):207-13
17048067
J Clin Endocrinol Metab. 2003 Jun;88(6):2573-8
12788857
Bone. 2002 Jul;31(1):43-50
12110411
J Clin Invest. 1993 Apr;91(4):1800-9
8473518
Nature. 1997 Mar 6;386(6620):78-81
9052783
Circ Res. 2006 Nov 10;99(10):1044-59
17095733
N Engl J Med. 1995 Feb 2;332(5):305-11
7816067
J Bone Miner Res. 2005 Nov;20(11):1912-20
16234963
Int J Cardiol. 2005 Oct 20;105(1):90-5
16207551
Calcif Tissue Int. 2006 Apr;78(4):195-202
16604285
Calcif Tissue Int. 2008 Aug;83(2):112-20
18612580
Osteoporos Int. 2007 Oct;18(10):1355-62
17492247
Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1998-2003
11742876
Cell. 1998 Apr 17;93(2):165-76
9568710
J Am Coll Cardiol. 2009 Dec 1;54(23):2129-38
19942084
N Engl J Med. 1999 Jan 14;340(2):115-26
9887164
Endocr Rev. 2002 Feb;23(1):90-119
11844745
Hypertens Res. 2008 Jun;31(6):1191-7
18716368
Calcif Tissue Int. 2008 Jun;82(6):411-7
18496724
J Nucl Cardiol. 2003 Mar-Apr;10(2):177-83
12673183
Ann Intern Med. 2006 Aug 15;145(4):255-64
16908916
Am J Med. 1999 May;106(5):506-12
10335721
Calcif Tissue Int. 2001 Jul;69(1):20-4
11685429
J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27
20338492
Osteoporos Int. 2011 Apr;22(4):1199-209
20533025
JAMA. 2009 Oct 21;302(15):1666-73
19843901
Lancet. 1996 Mar 16;347(9003):714-8
8602000
Mol Cell Biochem. 2007 Jan;295(1-2):45-52
16841180
Osteoporos Int. 1999;9(1):55-64
10367030
Calcif Tissue Int. 2002 Jun;70(6):443-9
11976772
Osteoporos Int. 2004 May;15(5):389-95
14661073
J Am Geriatr Soc. 1997 Feb;45(2):140-5
9033510
Osteoporos Int. 2001;12(4):259-65
11420774
Eur J Clin Invest. 2008 Apr;38(4):211-7
18279396
BMC Public Health. 2009 Oct 14;9:388
19828021
Calcif Tissue Int. 2006 Aug;79(2):102-11
16927045
Lancet. 1991 Aug 10;338(8763):355-8
1677708
Am J Cardiol. 2006 May 15;97(10):1427-8
16679077
Calcif Tissue Int. 2004 Feb;74(2):136-42
14668965
Arterioscler Thromb Vasc Biol. 2000 Aug;20(8):1926-31
10938013
J Thromb Haemost. 2003 Jan;1(1):178-85
12871556
Circ Res. 2002 Jul 12;91(1):9-16
12114316
Am J Epidemiol. 2004 Sep 15;160(6):549-56
15353415
J Clin Endocrinol Metab. 2002 Mar;87(3):1062-7
11889163
J Bone Miner Res. 2002 Jul;17(7):1245-55
12096838
J Womens Health (Larchmt). 2006 Apr;15(3):261-70
16620185
Ann Intern Med. 1994 Nov 1;121(9):641-7
7944071
J Exp Med. 2000 Aug 21;192(4):463-74
10952716
J Clin Invest. 1994 May;93(5):2106-13
8182141
Curr Opin Lipidol. 2001 Oct;12(5):555-60
11561176
JAMA. 1986 Nov 28;256(20):2835-8
3773200
Vasc Health Risk Manag. 2009;5(1):185-97
19436645
Biochem Biophys Res Commun. 2000 Sep 24;276(2):767-72
11027545
Bone. 2003 Jun;32(6):711-7
12810179
J Clin Endocrinol Metab. 2008 Oct;93(10):3927-35
18682515
J Am Coll Cardiol. 2008 Feb 12;51(6):627-33
18261681
J Clin Endocrinol Metab. 2004 Aug;89(8):3764-8
15292302
Atherosclerosis. 2006 Sep;188(1):196-202
16316658
Circ Res. 2006 Jul 21;99(2):156-64
16794190
J Am Geriatr Soc. 2004 Sep;52(9):1543-8
15341559
Calcif Tissue Int. 2007 Dec;81(6):430-41
17992559
N Engl J Med. 2005 Apr 21;352(16):1685-95
15843671
Calcif Tissue Int. 2006 Dec;79(6):431-42
17171500
Endocr Rev. 2004 Aug;25(4):629-72
15294885
Circulation. 2000 Mar 7;101(9):948-54
10704159
Rev Endocr Metab Disord. 2006 Jun;7(1-2):33-9
16960757
Calcif Tissue Int. 2004 Jan;74(1):12-7
14508624
Osteoporos Int. 2009 Dec;20(12):2071-8
19308300
J Biol Chem. 2001 Jun 8;276(23):20659-72
11274143
J Intern Med. 2006 Jun;259(6):598-605
16704561
Calcif Tissue Int. 2004 Oct;75(4):292-8
15549643
J Bone Miner Res. 2008 Oct;23(10):1601-12
18466072
J Am Geriatr Soc. 2004 Oct;52(10):1662-7
15450042
Am J Med. 1999 Mar;106(3):273-8
10190374
Circ Res. 2002 Oct 4;91(7):570-6
12364384
Calcif Tissue Int. 2007 Apr;80(4):244-50
17431532
Menopause. 2005 Nov-Dec;12(6):691-8
16278612
Calcif Tissue Int. 1998 Sep;63(3):190-6
9701621
Stroke. 1993 Jul;24(7):940-6
8322393
Stroke. 2009 Oct;40(10):3281-5
19661475
Atherosclerosis. 2003 Oct;170(2):333-7
14612215
QJM. 2005 Jul;98(7):467-84
15955801
Circulation. 2008 Jan 29;117(4):503-11
18180395
J Bone Miner Res. 2002 Oct;17(10):1744-51
12369777
Arterioscler Thromb Vasc Biol. 2001 Oct;21(10):1610-6
11597934
Mech Ageing Dev. 2005 Dec;126(12):1274-83
16144705
N Engl J Med. 2000 Mar 23;342(12):836-43
10733371
J Bone Miner Res. 2006 Dec;21(12):1839-46
17002567
J Clin Endocrinol Metab. 2007 Jun;92(6):2363-9
17374704
J Clin Endocrinol Metab. 2004 Sep;89(9):4246-53
15356016
Calcif Tissue Int. 2003 Jul;73(1):15-20
14506949
J Clin Invest. 1994 Jun;93(6):2393-402
8200973
Bone. 2002 Jun;30(6):849-52
12052452
Thromb Res. 2009 Nov;124(5):619-24
19660787
Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):e6-10
14670933
Stroke. 1998 Jul;29(7):1373-7
9660389
Stroke. 2001 Jan;32(1):47-51
11136913
J Gerontol A Biol Sci Med Sci. 2006 Feb;61(2):196-203
16510866
Menopause. 2009 Sep-Oct;16(5):937-43
19387416
Science. 2007 Mar 2;315(5816):1278-82
17332414
Osteoporos Int. 2005 Feb;16(2):184-90
15197541
Endocr Rev. 2001 Aug;22(4):477-501
11493580
Circ J. 2007 Oct;71(10):1555-9
17895551
Am J Epidemiol. 2009 Jan 15;169(2):186-94
19064643
Curr Med Res Opin. 2005 Sep;21(9):1355-61
16197653
J Womens Health (Larchmt). 2008 Apr;17(3):479-90
18345994
Free Radic Biol Med. 2001 Aug 15;31(4):509-19
11498284
Calcif Tissue Int. 2007 May;80(5):301-6
17505774