title: HIV and bone metabolism.
abstract: The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone by osteoblasts. In young adult humans and animals this process is homeostatic with no net gain or loss of bone mass. With natural aging and exacerbated by numerous pathological conditions, bone removal exceeds bone formation, disrupting homeostasis and resulting in bone loss. Over time, skeletal decline reaches clinical significance with development of osteopenia and eventually osteoporosis, conditions that dramatically increase bone fragility and the risk of fracture. Bone fractures can be devastating with significant morbidity and mortality. Over the last decade, it has become clear that skeletal renewal is strongly influenced by the immune system, a consequence of deep integration and centralization of common cell types and cytokine mediators, which we have termed the "immuno-skeletal interface." Consequently, dysregulated skeletal renewal and bone loss is a common feature of inflammatory conditions associated with immune activation. Interestingly, bone loss is also associated with conditions of immunodeficiency, including infection by the human immunodeficiency virus (HIV) that leads to acquired immunodeficiency syndrome (AIDS). Disruptions to the immuno-skeletal interface drive skeletal deterioration contributing to a high rate of bone fracture in HIV infection. This review examines current knowledge concerning the prevalence and etiology of skeletal complications in HIV infection, the effect of antiretroviral therapies (ART) on the skeleton, and how disruption of the immuno-skeletal interface may underlie bone loss in HIV infection and ART.
authors: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, 30322, USA.
authors: Ighovwerha
authors: I
authors: Ofotokun
authors: M Neale
authors: MN
authors: Weitzmann
references: Mech Ageing Dev. 1998 May 15;102(2-3):131-47
references: 9720647
references: J Clin Invest. 2003 Apr;111(8):1221-30
references: 12697741
references: AIDS. 2007 Mar 12;21(5):617-23
references: 17314524
references: Expert Opin Investig Drugs. 2010 Sep;19(9):1087-98
references: 20707594
references: Ann N Y Acad Sci. 2006 May;1067:66-82
references: 16803972
references: Clin Infect Dis. 2011 Apr 15;52(8):1061-8
references: 21398272
references: HIV Clin Trials. 2007 May-Jun;8(3):164-72
references: 17621463
references: J Clin Invest. 2004 Jul;114(2):206-13
references: 15254587
references: J Bone Miner Res. 1998 Dec;13(12):1915-23
references: 9844110
references: New Microbiol. 2010 Apr;33(2):109-15
references: 20518272
references: J Acquir Immune Defic Syndr. 2003 Jun 1;33 Suppl 2:S68-75
references: 12853855
references: AIDS Res Hum Retroviruses. 2007 Feb;23(2):243-50
references: 17331030
references: Osteoporos Int. 2007 Oct;18(10):1345-53
references: 17665239
references: Nature. 1999 Jan 28;397(6717):315-23
references: 9950424
references: Cell. 1997 Apr 18;89(2):309-19
references: 9108485
references: Lab Invest. 2008 Feb;88(2):171-84
references: 18040268
references: Adv Exp Med Biol. 2010;658:77-94
references: 19950018
references: J Clin Endocrinol Metab. 2008 Sep;93(9):3499-504
references: 18593764
references: N Engl J Med. 1998 Mar 26;338(13):853-60
references: 9516219
references: Clin Infect Dis. 2003 Feb 15;36(4):482-90
references: 12567307
references: Pediatrics. 2006 Sep;118(3):e711-8
references: 16923923
references: Nature. 1997 Nov 13;390(6656):175-9
references: 9367155
references: Expert Opin Pharmacother. 2007 May;8(7):923-33
references: 17472538
references: AIDS. 2003 Sep 5;17(13):1917-23
references: 12960824
references: Bone. 2011 May 1;48(5):1133-9
references: 21276883
references: J Bone Miner Res. 1995 Jun;10(6):890-902
references: 7572313
references: AIDS. 2009 Jul 31;23(12):1519-29
references: 19531929
references: AIDS. 2006 Nov 14;20(17):2165-74
references: 17086056
references: Nat Rev Immunol. 2009 Apr;9(4):235-45
references: 19319142
references: J Orthop Res. 2002 Nov;20(6):1185-9
references: 12472227
references: PLoS One. 2011 Feb 16;6(2):e17217
references: 21359191
references: AIDS. 2010 Nov 13;24(17):2679-86
references: 20859192
references: Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13848-53
references: 20643942
references: Immunol Rev. 2005 Dec;208:207-27
references: 16313351
references: AIDS. 2009 May 15;23(8):1021-4
references: 19300202
references: Curr Opin Infect Dis. 2010 Feb;23(1):1-8
references: 20010102
references: JAMA. 2004 Jul 14;292(2):191-201
references: 15249568
references: Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9271-6
references: 11481487
references: HIV Med. 2008 Feb;9(2):89-95
references: 18093130
references: Curr Opin Endocrinol Diabetes Obes. 2010 Dec;17(6):523-9
references: 20844427
references: Lancet. 1998 Nov 28;352(9142):1725-30
references: 9848347
references: J Periodontol. 1996 Oct;67(10 Suppl):1076-84
references: 8910826
references: J Immunol. 2006 Jan 1;176(1):625-31
references: 16365458
references: J Immunol. 1998 Dec 1;161(11):6113-21
references: 9834095
references: Blood. 2002 May 15;99(10):3702-6
references: 11986226
references: Lancet. 2010 Jan 9;375(9709):123-31
references: 20004464
references: Arch Biochem Biophys. 2010 Nov 1;503(1):66-77
references: 20682280
references: Rev Endocr Metab Disord. 2010 Dec;11(4):237-51
references: 21234807
references: J Bone Miner Res. 2007 Mar;22(3):465-75
references: 17144789
references: Injury. 2006 Aug;37(8):698-704
references: 16815394
references: Endocr Rev. 1995 Feb;16(1):87-116
references: 7758434
references: AIDS. 2001 Jan 5;15(1):137-8
references: 11192861
references: J Exp Med. 2008 Aug 4;205(8):1797-805
references: 18625747
references: Ann Intern Med. 2007 Jan 16;146(2):87-95
references: 17227932
references: J Infect Dis. 2009 Dec 1;200(11):1746-54
references: 19874178
references: Endocrinology. 1999 Sep;140(9):4367-70
references: 10465311
references: Antimicrob Agents Chemother. 2004 May;48(5):1469-87
references: 15105094
references: AIDS. 2000 Mar 10;14(4):F63-7
references: 10770534
references: AIDS. 2010 Nov 27;24(18):2827-33
references: 21045635
references: Clin Infect Dis. 2006 Jan 1;42(1):108-14
references: 16323100
references: HIV Med. 2011 Mar;12(3):157-65
references: 20722752
references: J Clin Endocrinol Metab. 2007 Mar;92(3):955-62
references: 17164302
references: HIV Clin Trials. 2003 Sep-Oct;4(5):337-46
references: 14583850
references: Ann N Y Acad Sci. 2007 Nov;1116:360-75
references: 18083938
references: Clin Infect Dis. 2010 Oct 15;51(8):937-46
references: 20839968
references: AIDS. 2009 Apr 27;23(7):817-24
references: 19363330
references: Immunol Rev. 2005 Dec;208:154-68
references: 16313347
references: J Acquir Immune Defic Syndr. 2009 Aug 15;51(5):554-61
references: 19512937
references: Top HIV Med. 2009 Sep-Oct;17(4):118-23
references: 19890183
references: J Pediatr. 2008 Apr;152(4):582-4
references: 18346519
references: AIDS. 2010 Sep 24;24(15):2337-45
references: 20683316
references: J Am Geriatr Soc. 1997 Mar;45(3):281-7
references: 9063272
references: Endocr Rev. 2000 Apr;21(2):115-37
references: 10782361
references: Blood. 2007 May 1;109(9):3839-48
references: 17202317
references: Clin Infect Dis. 2010 Oct 15;51(8):963-72
references: 20828304