title: Prevention of bone mineral density loss in patients with rheumatoid arthritis treated with anti-TNFalpha therapy.
abstract: This review focuses on recent advances in the effect of anti-TNFalpha therapy on bone metabolism and bone mineral density (BMD) in rheumatoid arthritis (RA). RA is a chronic disease characterized by inflammation of the synovial joint, cartilage degradation, and subsequent bone destruction. Bone damage is often manifested as erosions, localized juxta-articular bone loss, or generalized bone loss. Thus, blockade of TNFa not only serves to block inflammation, but also halts the erosive nature of RA and generalized/localized juxta-articular bone loss. Here, we review recent findings showing that anti-TNFa therapy is also effective on halting systemic bone loss. In vitro, TNFa reduces osteoblast activity and increases osteoclast activity through RANKL-RANK pathway. In arthritis animal models, an imbalance between bone formation and resorption is observed. In humans, this coupling of destruction is restored by anti-TNFalpha therapy early on, but only for a few months. Thus, anti-TNFalpha prevents the BMD loss in RA patients. In summary, TNFa blockade is not only able to prevent joint destruction, but it is also able to prevent bone loss in RA patients. Future studies are needed to address if TNFa blockers have an effect on bone fractures.
authors.affiliation: Clinical Immunology Unit, Departments of Immunology and Rheumatology, University of Lyon, and Unité Mixte Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Hérriot, Lyon, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Marotte
authors.forename: Pierre
authors.initials: P
authors.lastname: Miossec
references.citation: Ann Rheum Dis. 2005 Feb;64(2):336-7
references.pmid: 15647447
references.citation: Inflammation. 1992 Dec;16(6):587-601
references.pmid: 1459694
references.citation: Bone. 1999 Apr;24(4):381-5
references.pmid: 10221550
references.citation: Biochem Biophys Res Commun. 1998 Sep 29;250(3):776-81
references.pmid: 9784422
references.citation: Genes Dev. 1998 May 1;12(9):1260-8
references.pmid: 9573043
references.citation: Ann N Y Acad Sci. 2002 Jun;966:502-7
references.pmid: 12114311
references.citation: Arthritis Rheum. 2001 Jun;44(6):1254-60
references.pmid: 11407683
references.citation: J Biol Chem. 1997 Mar 28;272(13):8109-12
references.pmid: 9079619
references.citation: J Biol Chem. 1998 Jun 5;273(23):14363-7
references.pmid: 9603945
references.citation: J Clin Invest. 2002 Nov;110(10):1419-27
references.pmid: 12438440
references.citation: Br J Rheumatol. 1997 Jun;36(6):643-50
references.pmid: 9236673
references.citation: J Bone Miner Res. 1993 Jun;8(6):659-68
references.pmid: 8328307
references.citation: Bone. 2000 Apr;26(4):367-73
references.pmid: 10719280
references.citation: N Engl J Med. 1999 Jan 28;340(4):253-9
references.pmid: 9920948
references.citation: Am J Pathol. 2002 Oct;161(4):1419-27
references.pmid: 12368214
references.citation: Osteoporos Int. 2001;12(2):117-23
references.pmid: 11303711
references.citation: Ann Rheum Dis. 2006 Nov;65(11):1495-9
references.pmid: 16606653
references.citation: Curr Opin Rheumatol. 2004 Jul;16(4):428-34
references.pmid: 15201607
references.citation: Arthritis Rheum. 2001 Feb;44(2):253-9
references.pmid: 11229454
references.citation: J Bone Miner Metab. 2001;19(2):76-83
references.pmid: 11281163
references.citation: Rheumatol Int. 1984;4(1):1-8
references.pmid: 6718949
references.citation: N Engl J Med. 2006 Feb 23;354(8):821-31
references.pmid: 16495394
references.citation: J Clin Invest. 2003 Mar;111(6):821-31
references.pmid: 12639988
references.citation: J Rheumatol. 2003 Dec;30(12):2590-6
references.pmid: 14719199
references.citation: Ann Rheum Dis. 2001 May;60(5):521-2
references.pmid: 11302878
references.citation: Rheumatology (Oxford). 2005 Dec;44(12):1546-8
references.pmid: 16263785
references.citation: Arthritis Rheum. 2004 May;50(5):1400-11
references.pmid: 15146409
references.citation: Lymphokine Cytokine Res. 1991 Apr;10(1-2):15-21
references.pmid: 1873357
references.citation: Arthritis Rheum. 2005 Apr;52(4):1020-30
references.pmid: 15818697
references.citation: Arthritis Rheum. 2005 Aug;52(8):2307-12
references.pmid: 16052586
references.citation: Bone. 2002 Feb;30(2):428-35
references.pmid: 11856653
references.citation: Arthritis Rheum. 2002 Jun;46(6):1443-50
references.pmid: 12115173
references.citation: Arthritis Rheum. 2003 Oct;48(10):2996-7
references.pmid: 14558111
references.citation: Ann Rheum Dis. 2008 Jun;67(6):823-8
references.pmid: 17644545
references.citation: Arthritis Rheum. 2002 Mar;46(3):785-92
references.pmid: 11920416
references.citation: Ann Rheum Dis. 2008 Mar;67(3):353-7
references.pmid: 17644538
references.citation: Am J Pathol. 2001 Nov;159(5):1689-99
references.pmid: 11696430
references.citation: Rheumatology (Oxford). 2006 Jun;45(6):761-4
references.pmid: 16436492
references.citation: Ann Rheum Dis. 1995 Jan;54(1):49-52
references.pmid: 7880122
references.citation: Biochem Biophys Res Commun. 2000 Sep 7;275(3):768-75
references.pmid: 10973797
references.citation: J Bone Miner Res. 2000 Jul;15(7):1321-9
references.pmid: 10893680
references.citation: Arthritis Rheum. 2002 Jul;46(7):1744-53
references.pmid: 12124857
references.citation: Arthritis Res. 2000;2(1):33-7
references.pmid: 11094416
references.citation: Bone. 2004 Nov;35(5):1200-7
references.pmid: 15542046
references.citation: Arthritis Rheum. 2000 Oct;43(10):2178-88
references.pmid: 11037877
references.citation: Arthritis Rheum. 1993 Nov;36(11):1510-6
references.pmid: 8240428
references.citation: J Immunol. 1999 Aug 1;163(3):1521-8
references.pmid: 10415055
references.citation: J Bone Miner Res. 1996 Jun;11(6):707-30
references.pmid: 8725168
references.citation: Ann Rheum Dis. 1993 Jan;52(1):21-6
references.pmid: 8427509
references.citation: Best Pract Res Clin Rheumatol. 2001 Mar;15(1):105-23
references.pmid: 11358418
references.citation: Nature. 1999 Nov 18;402(6759):304-9
references.pmid: 10580503
references.citation: Arthritis Rheum. 2002 Jul;46(7):1720-8
references.pmid: 12124854
references.citation: J Bone Miner Res. 2003 May;18(5):859-67
references.pmid: 12733725
references.citation: Arthritis Rheum. 2006 Oct;54(10):3104-12
references.pmid: 17009229
references.citation: J Biol Chem. 2002 Jan 25;277(4):2695-701
references.pmid: 11723115
references.citation: Bone. 1997 Jul;21(1):17-21
references.pmid: 9213003
references.citation: Br J Rheumatol. 1994 Mar;33(3):224-30
references.pmid: 8156283
references.citation: Blood. 1998 May 15;91(10):3574-81
references.pmid: 9572991
references.citation: Best Pract Res Clin Rheumatol. 2003 Oct;17(5):729-52
references.pmid: 12915155
references.citation: Rev Rhum Engl Ed. 1997 Mar;64(3):153-9
references.pmid: 9090763
references.citation: Endocrinology. 2000 Nov;141(11):3956-64
references.pmid: 11089525
references.citation: J Clin Invest. 2000 Nov;106(10):1229-37
references.pmid: 11086024
references.citation: Nature. 1986 Feb 6-12;319(6053):516-8
references.pmid: 3511389
references.citation: Br J Rheumatol. 1994 Jun;33(6):541-5
references.pmid: 8205401
references.citation: Lancet. 1994 Jul 2;344(8914):23-7
references.pmid: 7912297
references.citation: Ann Rheum Dis. 2004 Jan;63(1):15-22
references.pmid: 14672886
references.citation: Clin Exp Rheumatol. 2000 Nov-Dec;18(6):683-90
references.pmid: 11138329
references.citation: Z Rheumatol. 2000;59 Suppl 1:33-8
references.pmid: 10769433
references.citation: J Exp Med. 2000 Aug 21;192(4):463-74
references.pmid: 10952716
references.citation: Arthritis Rheum. 2000 Feb;43(2):250-8
references.pmid: 10693863
references.citation: J Immunol. 1999 Nov 1;163(9):5049-55
references.pmid: 10528210
references.citation: Endocrinology. 1997 Sep;138(9):3849-58
references.pmid: 9275074
references.citation: J Clin Invest. 1997 Apr 1;99(7):1699-703
references.pmid: 9120014
references.citation: J Biol Chem. 2001 Jun 8;276(23):20659-72
references.pmid: 11274143
references.citation: J Bone Miner Res. 1999 Sep;14(9):1478-85
references.pmid: 10469275
references.citation: Lancet. 1999 Dec 4;354(9194):1932-9
references.pmid: 10622295
references.citation: Am J Pathol. 1998 Apr;152(4):943-51
references.pmid: 9546355
references.citation: Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii84-6
references.pmid: 12379632
references.citation: J Bone Miner Res. 1998 May;13(5):793-802
references.pmid: 9610743
references.citation: Osteoporos Int. 1993;3 Suppl 1:106-7
references.pmid: 8461533
references.citation: Ann Rheum Dis. 1995 Oct;54(10):801-6
references.pmid: 7492217
references.citation: Arthritis Res Ther. 2005;7(1):R149-55
references.pmid: 15642135
references.citation: Am J Gastroenterol. 2005 Sep;100(9):2031-5
references.pmid: 16128948
references.citation: J Bone Miner Res. 2001 Feb;16(2):348-60
references.pmid: 11204435
references.citation: Arthritis Res Ther. 2007;9(3):R61
references.pmid: 17597527
references.citation: BMJ. 1993 Feb 27;306(6877):558
references.pmid: 8461772
references.citation: Immunol Today. 2000 Oct;21(10):495-502
references.pmid: 11071528
references.citation: Ann Rheum Dis. 2005 Aug;64(8):1137-40
references.pmid: 15642695
references.citation: Arthritis Rheum. 2000 Nov;43(11):2523-30
references.pmid: 11083276
references.citation: J Rheumatol. 1999 Jun;26(6):1250-6
references.pmid: 10381038
references.citation: Arthritis Rheum. 2000 Feb;43(2):259-69
references.pmid: 10693864
references.citation: N Engl J Med. 2000 Nov 30;343(22):1594-602
references.pmid: 11096166
references.citation: Arthritis Rheum. 1987 Jul;30(7):721-8
references.pmid: 3619959
references.citation: Ann Rheum Dis. 2003 Apr;62(4):347-9
references.pmid: 12634235