HIV/hepatitis C co-infection increases risk of hip fracture

Michael Carter
Published: 19 June 2012

Co-infection with HIV and hepatitis C is associated with an increased risk of hip fracture, US investigators report in Hepatology. Hepatitis C monoinfection also increased the risk of this type of fracture. The authors suggest that this elevation in the risk of fracture could be caused by the inflammatory effects of these infections, but they also think that social and lifestyle factors are likely to be important contributory factors.

“Additional research is needed to determine the mechanisms by which chronic HCV [hepatitis C virus] and HCV/HIC co-infection affect bone mineral density and fracture incidence,” write the authors.

Infection with hepatitis C has been associated with reduced bone mineral density. This is also the case for HIV infection, as well as for some antiretroviral drugs, most especially tenofovir (Viread, also in the combination pills Truvada, Atripla and Eviplera). However, the association between the reduced bone mineral density seen in the context of hepatitis C monoinfection and HIV/hepatitis C co-infection and fracture risk is unclear.

Investigators from the US therefore designed a large prospective study comparing the incidence and risk of hip fracture in over 3 million patients according to their HIV and hepatitis C infection status.

They selected hip fracture because of its association with reduced bone mineral density, and also because of its association with increased mortality risk.

Their study sample included 3,111,000 uninfected patients; 277,000 hepatitis C-monoinfected individuals; 96,000 patients with HIV monoinfection; and 37,000 individuals with HIV/hepatitis C co-infection. All received care between 1999 and 2005.

There were important differences in the characteristics of the participants with hepatitis C monoinfection and individuals with HIV monoinfection and HIV/hepatitis C co-infection.

The hepatitis C monoinfected participants were older, more likely to be women and were more commonly of white race. In addition, compared to patients with HIV monoinfection, those with hepatitis C monoinfection were significantly more likely to have medical conditions associated with an increased risk of low bone mineral density or falls. These included alcoholism, asthma, cardiovascular disease, diabetes, chronic kidney disease and rheumatoid arthritis.

Incidence of hip fracture was lowest among participants with neither infection (1.29 per 1000 patient-years). It increased in the context of HIV monoinfection (1.95 per 1000 patient-years) and hepatitis C monoinfection (2.69 per 1000 patient-years). It was highest of all in co-infected patients (3.06 per 1000 patient-years).

After adjusting for factors such as age, sex and the presence of other factors associated with osteoporosis or fall, the investigators found that co-infection was associated with an increased risk of fracture compared to hepatitis C monoinfection (HR = 1.38; 95% CI, 1.25-1.53).

Co-infected participants were also more likely to experience a hip fracture than people with HIV monoinfection (females, HR = 1.76; 95% CI, 1.44-2.16; males, HR = 1.36; 95% CI, 1.20-1.55). The risk of fracture was also higher in comparison to uninfected participants (females, HR = 2.65; 95% CI, 2.21-3.17; males, HR = 2.20; 95% CI, 1.97-2.47).

Hepatitis C monoinfection was associated with an increased risk of hip fracture compared to HIV-monoinfected and uninfected participants, especially for people aged between 19 and 39 (females, HR = 3.56; 95% CI, 2.93-4.32; males, HR = 2.40; 95% CI, 2.02-2.84).

“HCV/HIV co-infection was associated with increased rates of hip fracture compared to HCV-monoinfected, HIV-monoinfected, and HCV/HIV-uninfected persons,” comment the investigators. “HCV-monoinfected patients had an increased risk of hip fracture compared to uninfected individuals.”

The study did not show why this was the case. Nevertheless, the investigators believe it could be because of the inflammatory effects of HIV and hepatitis C. “The higher fracture rates observed among HCV/HIV-co-infected persons compared to HCV-monoinfected individuals might be due to the additive effects of HIV infection and antiretroviral therapy on bone mineral density.”

But the researchers also believe that other factors are likely to be important. “Illicit drug use, alcohol abuse, poor nutrition, and fragility among HCV-infected patients might also contribute to increased risk from trauma, irrespective of the impact of HCV infection on bone mineral density.”

The authors therefore suggest that “additional research is needed to determine the mechanisms by which chronic HCV and HCV/HIV co-infection affect bone mineral density and fracture incidence”.


Lo Re V et al. Risk of hip fracture associated with hepatitis C virus infection and hepatitis C/HIV coinfection. Hepatology, online edition. DOI: 10.0112/hep25866, 2012.

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