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
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
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
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
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”.