The Differential Effects of Human Immunodeficiency Virus and Hepatitis C Virus on Bone Microarchitecture and Fracture Risk

Background Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected individuals have a significantly greater osteoporotic fracture risk than HIV-monoinfected persons, despite the fact that HIV/HCV coinfection has not been associated with lower bone mineral density (BMD) than HIV or HCV alone. To evaluate if changes in bone microarchitecture, measured by trabecular bone score (TBS), could explain these differences, we performed a prospective, cross-sectional cohort study of virologically suppressed HIV-infected subjects, untreated HCV-infected subjects, HIV/HCV-coinfected subjects, and uninfected controls. Methods We enrolled 532 male subjects: 57 HIV/HCV coinfected, 174 HIV infected, 123 HCV infected, and 178 controls. We conducted analysis of covariance comparing BMD and TBS between groups, controlling for age, race, body mass index, and smoking. We used linear regression to evaluate predictors of BMD and TBS and evaluated the effects of severity of HCV infection and tenofovir disoproxil fumarate use. Results Despite both infections being associated with decreased BMD, only HCV, but not HIV, was associated with lower TBS score. Also, HIV/HCV-coinfected subjects had lower TBS scores than HIV-monoinfected, HCV-monoinfected, and uninfected subjects. Neither the use of TDF or HCV viremia nor the severity of HCV liver disease was associated with lower TBS. Conclusions HCV infection is associated with microarchitectural changes at the lumbar spine as assessed by the low TBS score, suggesting that microstructural abnormalities underlie some of the higher fracture risk in HCV infection. TBS might improve fracture risk prediction in HCV infection.

[1]  R. Weber,et al.  Hepatitis C Infection and the Risk of Non-Liver-Related Morbidity and Mortality in HIV-Infected Persons in the Swiss HIV Cohort Study , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  Jacques P. Brown,et al.  A Meta‐Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX , 2016, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  P. Tebas,et al.  Mechanisms of bone disease in HIV and hepatitis C virus: impact of bone turnover, tenofovir exposure, sex steroids and severity of liver disease , 2016, AIDS.

[4]  M. Yin,et al.  Osteoporosis and fractures in HIV/hepatitis C virus coinfection: a systematic review and meta-analysis , 2014, AIDS.

[5]  Heinrich Resch,et al.  Trabecular Bone Score: A Noninvasive Analytical Method Based Upon the DXA Image , 2014, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  P. Tebas,et al.  Hepatitis C Co‐infection and Severity of Liver Disease as Risk Factors for Osteoporotic Fractures Among HIV‐Infected Patients , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[7]  D. Neau,et al.  Chronic Viral Hepatitis Is Associated With Low Bone Mineral Density in HIV-Infected Patients, ANRS CO 3 Aquitaine Cohort , 2013, Journal of acquired immune deficiency syndromes.

[8]  C. Sabin,et al.  Impact of switching from zidovudine to tenofovir disoproxil fumarate on bone mineral density and markers of bone metabolism in virologically suppressed HIV-1 infected patients; a substudy of the PREPARE study. , 2013, The Journal of clinical endocrinology and metabolism.

[9]  Jeannie S. Huang,et al.  Fractures after antiretroviral initiation , 2012, AIDS.

[10]  A. Localio,et al.  Risk of hip fracture associated with hepatitis c virus infection and hepatitis C/human immunodeficiency virus coinfection , 2012, Hepatology.

[11]  P. Tebas,et al.  Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents , 2012, AIDS.

[12]  S. Gange,et al.  Assessing mortality in women with hepatitis C virus and HIV using indirect markers of fibrosis , 2012, AIDS.

[13]  C. Larsen,et al.  Incidence of low and high-energy fractures in persons with and without HIV infection: a Danish population-based cohort study , 2012, AIDS.

[14]  Richard D Moore,et al.  Controlled HIV viral replication, not liver disease severity associated with low bone mineral density in HIV/HCV co-infection. , 2011, Journal of hepatology.

[15]  P. Sax,et al.  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. , 2011, The Journal of infectious diseases.

[16]  K. Buchacz,et al.  Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the US general population, 2000-2006. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  Joseph L. Goulet,et al.  Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans , 2011, PloS one.

[18]  Mary Young,et al.  Fracture incidence in HIV-infected women: results from the Women's Interagency HIV Study , 2010, AIDS.

[19]  H. Stellbrink,et al.  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. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  D. Cooper,et al.  Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-Lamivudine: a randomized, 96-week trial. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  A. Localio,et al.  Viral hepatitis is associated with reduced bone mineral density in HIV-infected women but not men , 2009, AIDS.

[22]  T. Brown,et al.  Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. , 2008, The Journal of clinical endocrinology and metabolism.

[23]  Mardge H. Cohen,et al.  The association of bone mineral density with HIV infection and antiretroviral treatment in women , 2007, Antiviral therapy.

[24]  H. Sørensen,et al.  Cause-Specific Excess Mortality in Siblings of Patients Co-Infected with HIV and Hepatitis C Virus , 2007, PloS one.

[25]  H. Sørensen,et al.  Mortality in siblings of patients coinfected with HIV and hepatitis C virus. , 2007, The Journal of infectious diseases.

[26]  T. Brown,et al.  Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review , 2006, AIDS.

[27]  R. Porcher,et al.  Diagnosis of vertebral fractures by vertebral fracture assessment. , 2006, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[28]  I. Schiefke,et al.  Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection. , 2005, World journal of gastroenterology.

[29]  W. Leslie,et al.  AGA technical review on osteoporosis in hepatic disorders. , 2003, Gastroenterology.

[30]  J. Kalbfleisch,et al.  A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C , 2003, Hepatology.

[31]  J. Kanis,et al.  Diagnosis of osteoporosis and assessment of fracture risk , 2002, The Lancet.

[32]  K. Yarasheski,et al.  Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy , 2000, AIDS.