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Published in: Osteoporosis International 1/2017

01-01-2017 | Original Article

Factors associated with fractures in HIV-infected persons: which factors matter?

Authors: L. Gedmintas, E. A. Wright, Y. Dong, E. Lehmann, J. N. Katz, D. H. Solomon, E. Losina

Published in: Osteoporosis International | Issue 1/2017

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Abstract

Summary

This study aims to determine what factors are associated with increased risk of fracture among patients with HIV, in particular whether an important medication used to treat HIV, tenofovir, is associated with fracture. Our study found that while co-infection with hepatitis C and markers of HIV severity were associated with fracture, tenofovir was not.

Introduction

Growing evidence suggests that tenofovir disoproxil fumarate decreases bone density among patients with HIV, but there are conflicting reports as to whether this decrease in bone density translates to higher fracture risk. We aimed to determine what factors were associated with an increased risk of fracture for patients with HIV, in particular whether tenofovir is associated with elevated fracture risk.

Methods

We conducted a retrospective cohort study at two tertiary care hospitals in Boston, MA, between 2001 and 2012 to determine whether tenofovir use is associated with elevated all-site fracture risk, as compared to other antiretroviral medications. We also examined other potential factors associated with fracture among patients with HIV.

Results

We identified 1981 HIV-infected patients who had at some point used tenofovir and 682 patients who had not. The mean age was 43 years, and 72 % were male. The hepatitis C co-infection rate was 28 %, about 40 % had nadir CD4 count <200, and about 40 % had a history of an AIDS-defining illness. We did not find an association between risk of fracture and tenofovir disoproxil fumarate (TDF) (adjusted RR (aRR) 0.8, 95 % CI 0.6–1.1). However, co-infection with hepatitis C did increase risk of fracture (aRR 1.6, 95 % CI 1.1–2.3), as did nadir CD4 count <200 (aRR 3.1, 95 % CI 1.9–5.0) and history of AIDS-defining illness (aRR 1.6, 95 % CI 1.1–2.2).

Conclusion

There was no association found between fracture and tenofovir use, but there were associations between co-infection with hepatitis C and markers of advanced HIV disease and fracture.
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Literature
1.
go back to reference Brown TT, Qaqish RB (2006) Antiretroviral therapy and the prevalence of osteopeania and osteoporosis: a meta-analytic review. AIDS 20(17):2165–2174CrossRefPubMed Brown TT, Qaqish RB (2006) Antiretroviral therapy and the prevalence of osteopeania and osteoporosis: a meta-analytic review. AIDS 20(17):2165–2174CrossRefPubMed
2.
go back to reference Triant VA, Brown TT, Lee H, Grinspoon SK (2008) Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 93(9):3499–3504CrossRefPubMedPubMedCentral Triant VA, Brown TT, Lee H, Grinspoon SK (2008) Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 93(9):3499–3504CrossRefPubMedPubMedCentral
3.
go back to reference Womack JA, Goulet JL, Gibert C et al (2011) Increased risk of fragility fractures among HIV infected compared to uninfected male veterans. PLoS ONE 6(2), e17217CrossRefPubMedPubMedCentral Womack JA, Goulet JL, Gibert C et al (2011) Increased risk of fragility fractures among HIV infected compared to uninfected male veterans. PLoS ONE 6(2), e17217CrossRefPubMedPubMedCentral
4.
go back to reference Young B, Dao CN, Buchacz K, Baker R, Brooks JT (2011) Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the US general population, 2000-2006. Clin Infect Dis 52(8):1061–1068CrossRefPubMed Young B, Dao CN, Buchacz K, Baker R, Brooks JT (2011) Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the US general population, 2000-2006. Clin Infect Dis 52(8):1061–1068CrossRefPubMed
5.
go back to reference Hansen AB, Gerstoft J, Kronborg G et al (2012) Incidence of low and high-energy fractures in persons with and without HIV infection: a Danish population-based cohort study. AIDS 26(3):285–293CrossRefPubMed Hansen AB, Gerstoft J, Kronborg G et al (2012) Incidence of low and high-energy fractures in persons with and without HIV infection: a Danish population-based cohort study. AIDS 26(3):285–293CrossRefPubMed
6.
go back to reference Guerri-Fernandez R, Vestergaard P, Carbonell C et al (2013) HIV infection is strongly associated with hip fracture risk, independently of age, gender, and comorbidities: a population-based cohort study. J Bone Miner Res 28(6):1259–1263CrossRefPubMed Guerri-Fernandez R, Vestergaard P, Carbonell C et al (2013) HIV infection is strongly associated with hip fracture risk, independently of age, gender, and comorbidities: a population-based cohort study. J Bone Miner Res 28(6):1259–1263CrossRefPubMed
7.
go back to reference Horvath KJ, Eastman M, Prosser R, Goodroad B, Worthington L (2012) Addressing smoking during medical visits: patients with human immunodeficiency virus. Am J Prev Med 43(5 Suppl 3):S214–S221CrossRefPubMed Horvath KJ, Eastman M, Prosser R, Goodroad B, Worthington L (2012) Addressing smoking during medical visits: patients with human immunodeficiency virus. Am J Prev Med 43(5 Suppl 3):S214–S221CrossRefPubMed
8.
go back to reference Tesoriero JM, Gieryic SM, Carrascal A, Lavigne HE (2010) Smoking among HIV positive New Yorkers: prevalence, frequency, and opportunities for cessation. AIDS Behav 14(4):824–835CrossRefPubMed Tesoriero JM, Gieryic SM, Carrascal A, Lavigne HE (2010) Smoking among HIV positive New Yorkers: prevalence, frequency, and opportunities for cessation. AIDS Behav 14(4):824–835CrossRefPubMed
9.
go back to reference Sherman KE, Rouster SD, Chung RT, Rajicic N (2002) Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis 34(6):831–837CrossRefPubMed Sherman KE, Rouster SD, Chung RT, Rajicic N (2002) Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis 34(6):831–837CrossRefPubMed
10.
go back to reference Lau B, Sharrett AR, Kingsley LA et al (2006) C-reactive protein is a marker for human immunodeficiency virus disease progression. Arch Intern Med 166(1):64–70CrossRefPubMed Lau B, Sharrett AR, Kingsley LA et al (2006) C-reactive protein is a marker for human immunodeficiency virus disease progression. Arch Intern Med 166(1):64–70CrossRefPubMed
12.
go back to reference Schett G, Kiechl S, Weger S et al (2006) High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med 166(22):2495–2501CrossRefPubMed Schett G, Kiechl S, Weger S et al (2006) High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med 166(22):2495–2501CrossRefPubMed
13.
go back to reference Vikulina T, Fan X, Yamaguchi M et al (2010) Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats. Proc Natl Acad Sci U S A 107(31):13848–13853CrossRefPubMedPubMedCentral Vikulina T, Fan X, Yamaguchi M et al (2010) Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats. Proc Natl Acad Sci U S A 107(31):13848–13853CrossRefPubMedPubMedCentral
14.
go back to reference Bonjoch A, Figueras M, Estany C et al (2010) High prevalence of and progression to low bone mineral density in HIV-infected patients: a longitudinal cohort study. AIDS 24(18):2827–2833CrossRefPubMed Bonjoch A, Figueras M, Estany C et al (2010) High prevalence of and progression to low bone mineral density in HIV-infected patients: a longitudinal cohort study. AIDS 24(18):2827–2833CrossRefPubMed
15.
go back to reference Calmy A, Fux CA, Norris R et al (2009) Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study. J Infect Dis 200(11):1746–1754CrossRefPubMed Calmy A, Fux CA, Norris R et al (2009) Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study. J Infect Dis 200(11):1746–1754CrossRefPubMed
16.
go back to reference Duvivier C, Kolta S, Assoumou L et al (2009) Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS 23(7):817–824CrossRefPubMed Duvivier C, Kolta S, Assoumou L et al (2009) Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS 23(7):817–824CrossRefPubMed
17.
go back to reference McComsey GA, Kitch D, Daar ES et al (2011) Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis 203(12):1791–1801CrossRefPubMedPubMedCentral McComsey GA, Kitch D, Daar ES et al (2011) Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis 203(12):1791–1801CrossRefPubMedPubMedCentral
18.
go back to reference Stellbrink HJ, Orkin C, Arribas JR et al (2010) Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis 51(8):963–972CrossRefPubMed Stellbrink HJ, Orkin C, Arribas JR et al (2010) Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis 51(8):963–972CrossRefPubMed
19.
go back to reference Mundy LM, Youk AO, McComsey GA, Bowlin SJ (2012) Overall benefit of antiretroviral treatment on the risk of fracture in HIV: nested case-control analysis in a health-insured population. AIDS 26(9):1073–1082CrossRefPubMed Mundy LM, Youk AO, McComsey GA, Bowlin SJ (2012) Overall benefit of antiretroviral treatment on the risk of fracture in HIV: nested case-control analysis in a health-insured population. AIDS 26(9):1073–1082CrossRefPubMed
20.
go back to reference Bedimo R, Maalouf NM, Zhang S, Drechsler H, Tebas P (2012) Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents. AIDS 26(7):825–831CrossRefPubMed Bedimo R, Maalouf NM, Zhang S, Drechsler H, Tebas P (2012) Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents. AIDS 26(7):825–831CrossRefPubMed
21.
go back to reference Yin MT, Shi Q, Hoover DR et al (2010) Fracture incidence in HIV-infected women: results from the Women’s Interagency HIV Study. AIDS 24(17):2679–2686CrossRefPubMedPubMedCentral Yin MT, Shi Q, Hoover DR et al (2010) Fracture incidence in HIV-infected women: results from the Women’s Interagency HIV Study. AIDS 24(17):2679–2686CrossRefPubMedPubMedCentral
22.
go back to reference Yong MK, Elliott JH, Woolley IJ, Hoy JF (2011) Low CD4 count is associated with an increased risk of fragility fracture in HIV-infected patients. J Acquir Immune Defic Syndr 57(3):205–210CrossRefPubMed Yong MK, Elliott JH, Woolley IJ, Hoy JF (2011) Low CD4 count is associated with an increased risk of fragility fracture in HIV-infected patients. J Acquir Immune Defic Syndr 57(3):205–210CrossRefPubMed
23.
go back to reference Gedmintas L, Wright EA, Losina E, Katz JN, Solomon DH (2014) Comparative risk of fracture in men and women with HIV. J Clin Endocrinol Metab 99(2):486–490CrossRefPubMed Gedmintas L, Wright EA, Losina E, Katz JN, Solomon DH (2014) Comparative risk of fracture in men and women with HIV. J Clin Endocrinol Metab 99(2):486–490CrossRefPubMed
24.
go back to reference Solomon DH, Mercer E, Kavanaugh A (2012) Observational studies on the risk of cancer associated with tumor necrosis factor inhibitors in rheumatoid arthritis: a review of their methodologies and results. Arthritis Rheum 64(1):21–32CrossRefPubMedPubMedCentral Solomon DH, Mercer E, Kavanaugh A (2012) Observational studies on the risk of cancer associated with tumor necrosis factor inhibitors in rheumatoid arthritis: a review of their methodologies and results. Arthritis Rheum 64(1):21–32CrossRefPubMedPubMedCentral
25.
go back to reference Winthrop KL, Baddley JW, Chen L et al (2013) Association between the initiation of anti-tumor necrosis factor therapy and the risk of herpes zoster. JAMA 309(9):887–895CrossRefPubMedPubMedCentral Winthrop KL, Baddley JW, Chen L et al (2013) Association between the initiation of anti-tumor necrosis factor therapy and the risk of herpes zoster. JAMA 309(9):887–895CrossRefPubMedPubMedCentral
26.
go back to reference Black DM, Reiss TF, Nevitt MC, Cauley J, Karpf D, Cummings SR (1993) Design of the Fracture Intervention Trial. Osteoporos Int 3(Suppl 3):S29–S39CrossRefPubMed Black DM, Reiss TF, Nevitt MC, Cauley J, Karpf D, Cummings SR (1993) Design of the Fracture Intervention Trial. Osteoporos Int 3(Suppl 3):S29–S39CrossRefPubMed
27.
go back to reference Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services: Panel on Antiretroviral Guidelines for Adults and Adolescents Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services: Panel on Antiretroviral Guidelines for Adults and Adolescents
28.
go back to reference Casado JL, Santiuste C, Vazquez M, Baon S, Rosillo M, Gomez A, Perez-Elias MJ, Cabellero C, Rey JM, Moreno S (2016) Bone mineral density decline according to renal tubular dysfunction and phosphaturia in tenofovir-exposed HIV-infected patients. AIDS 30(9):1423–1431CrossRefPubMed Casado JL, Santiuste C, Vazquez M, Baon S, Rosillo M, Gomez A, Perez-Elias MJ, Cabellero C, Rey JM, Moreno S (2016) Bone mineral density decline according to renal tubular dysfunction and phosphaturia in tenofovir-exposed HIV-infected patients. AIDS 30(9):1423–1431CrossRefPubMed
29.
go back to reference Sax PE, Wohl D, Yin MT et al (2015) Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet 385(9987):2606–2615CrossRefPubMed Sax PE, Wohl D, Yin MT et al (2015) Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet 385(9987):2606–2615CrossRefPubMed
30.
go back to reference Dong HV, Cortes YI, Shiau S, Yin MT (2014) Osteoporosis and fractures in HIV/hepatitis C virus coinfection: a systematic review and meta-analysis. AIDS 28(14):2119–2131CrossRefPubMedPubMedCentral Dong HV, Cortes YI, Shiau S, Yin MT (2014) Osteoporosis and fractures in HIV/hepatitis C virus coinfection: a systematic review and meta-analysis. AIDS 28(14):2119–2131CrossRefPubMedPubMedCentral
31.
go back to reference Cutrell J, Zhang S, Drechsler H, Tebas P, Maalouf N, Bedimo R (2015) Evaluation and management of fracture risk in HIV patients in the VA system. International AIDS Society; Vancouver, Canada Cutrell J, Zhang S, Drechsler H, Tebas P, Maalouf N, Bedimo R (2015) Evaluation and management of fracture risk in HIV patients in the VA system. International AIDS Society; Vancouver, Canada
Metadata
Title
Factors associated with fractures in HIV-infected persons: which factors matter?
Authors
L. Gedmintas
E. A. Wright
Y. Dong
E. Lehmann
J. N. Katz
D. H. Solomon
E. Losina
Publication date
01-01-2017
Publisher
Springer London
Published in
Osteoporosis International / Issue 1/2017
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-016-3704-6

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