Infection with hepatitis C virus (HCV) and HIV causes inflammation, a natural response by the immune system as it seeks to deal with invading germs. However, sometimes the sheer number of germs overwhelms the immune system or at other times the germs are able to subvert the immune system's response to infection. In such cases, the germs spread and infection takes hold. This can be the case with viral infections and when such an infection becomes established in the body, it becomes a chronic infection.
Even in cases of chronic viral infections the immune system tries to fight the infection, but inflammation that may have been useful in the initial stages of exposure becomes a problem if it is sustained over the long-term.
The immune system and its cells are widely distributed throughout the body and found within many organ-systems such as the following:
brain
bones
cardiovascular system
liver
lungs
kidneys
A chronic viral infection with its associated inflammation of the immune system is likely to cause inflammation-related problems for these organ-systems.
HCV and Bones
The inflammation caused by chronic HCV infection affects the liver, causing this organ to become dysfunctional and injured. HCV can also cause other problems; for instance, some studies have found thinner-than-normal bones in some HCV-positive people.
Some researchers think that this problem of bone thinning in HCV infection arises in part because of complications of liver injury and chronic liver inflammation. An injured and inflamed liver could result in reduced levels of the hormones estrogen and testosterone. These hormones play an important role in maintaining the health of bones. Also, a dysfunctional liver may not be able to convert vitamin D to its active form. This may affect the body's ability to absorb and retain nutrients such as calcium and phosphorus, which are needed to build bones.
HIV and Bones
Potent combination anti-HIV therapy (commonly called ART or HAART) can also temporarily decrease the thickness of bones (called bone mineral density) in the first few years of use. However, after this, bone mineral density tends to stabilize. The reason for the initially decreased bone mineral density under ART is not yet clear. But the benefits of ART continue to greatly outweigh the risks.
Focus on the Hips
A team of researchers in the U.S. has grown concerned about the strength of bones in the hips of people with HCV, HIV or both viral infections. Among HIV-negative people, when hip bones/joints become broken their survival subsequently decreases. Moreover, the U.S. researchers noted:
"Hip fractures cause significant pain and disability and typically require an emergency department visit, hospitalization, surgery and rehabilitation stay, resulting in substantial healthcare costs."
The U.S. research team (based at the University of Pennsylvania) conducted a massive study of three million people, both with and without different viral infections. They found that people co-infected with HIV and HCV were at greatest risk of hip fracture compared to participants with HCV infection alone (monoinfection) or to people who had neither infection.
This study underscores the need to understand why thinning bones, particularly in the hips, occur in people with HIV, HCV or both. Furthermore, ways to improve the bone health of people with chronic viral infections are needed.
Study Details
Researchers at hospitals in Philadelphia and Boston collaborated on a massive cohort study, analysing health related-information collected from adults using the U.S. Medicaid program in the following states:
California
Florida
New York
Ohio
Pennsylvania
The research team compared data assembled on each person with HCV monoinfection, HIV monoinfection and both infections (co-infection) and compared them to health-related data collected from up to 10 randomly selected people without viral infections.
The researchers analysed data collected from more than three million people distributed as follows:
HCV monoinfection: 276,901 participants
HIV monoinfection: 95,827 participants
HIV-HCV co-infection: 36,950 participants
uninfected people: 2,744,075 participants
On average, participants were in their early 40s, and 60% were men and 40% women. They were monitored for up to seven years.
Results -- Other Conditions and Medicines
The study team found that it was relatively common for HCV-positive people to have been diagnosed with conditions that were either associated with severely thin bones (osteoporosis) or a risk of falling, including the following:
alcoholism
asthma
cardiovascular disease
type II diabetes
kidney disease
excessive levels of parathyroid hormone
rheumatoid arthritis
They also found that participants with HCV monoinfection were more likely than other groups in the study to have received medicines associated with thinning bones, including the following drugs:
corticosteroids
a group of acid-reducing agents called proton pump inhibitors
Results -- Comparing Fracture Risks Between People With and Without HCV
Overall, HCV-positive people had a 47% increased risk of hip fracture compared to uninfected people. However, it is important to note that this risk varied, in some cases, by factors such as age and gender among HCV-positive people, as follows:
Age: More than 70 years
No increased risk of hip fractures due to HCV monoinfection were seen.Age: Less than 70 years
There was an increased risk for hip fracture due to HCV monoinfection.Age: 18 to 39 years
There was nearly a four-fold increased risk for hip fracture among women and slightly more than a two-fold increased risk for men.
Results -- Comparing Fracture Risks Between Co-Infected and Uninfected People
Overall, ART-treated participants had a greater risk for hip fracture (about two-fold) compared to uninfected people. In general, for co-infected men and women fracture risk rose with age.
Results -- Comparing Fracture Risks Between Co-Infected People and People With HIV Monoinfection
Overall, ART-using co-infected participants had a greater risk for hip fracture than ART-using participants with HIV monoinfection. This increased risk differed by gender, with co-infected ART-using women having a 76% increased risk and co-infected ART-using men having a 36% increased risk for hip fracture.
Results -- Comparing Fracture Risks Between Co-Infected People and People With HCV Monoinfection
Among all HIV-HCV co-infected people, there was a 38% increased risk for hip fracture compared to HCV-monoinfected people.
Key Findings
1. HIV-HCV co-infected people who use ART have increased risk for hip fractures compared to the following groups of people:
HCV monoinfection
HIV moninfection + use of ART
people who have neither HIV nor HCV
2. HCV-monoinfected people have increased risk for hip fracture compared to people without HCV (or HIV) who are under the age of 70.
Viral Infections and Bones
Researchers are not certain why there was an increased risk for hip fractures among HCV-positive people. We have already mentioned the potential impact of chronic inflammation and liver injury on bone health. However, more research needs to be done to fully understand the general impact of chronic HCV infection on bone health.
Other Factors That Could Have Affected Bone Health
The research team noted that certain factors that are relatively common among some HCV-positive people could also play a role in the loss of bone mineral density, including the following:
use of street drugs
smoking
excessive intake of alcohol
poor nutrition
length of time infected with HCV or HIV
Their data set did not include these missing factors and that is one weakness that may have affected the study's conclusions.
Focus on HIV and Its Treatment
Other studies have found that HIV-positive people (and even some people at high risk for HIV infection) tend to have reduced bone mineral density. The reason(s) for this are not clear. Chronic HIV infection also causes inflammation that is only partially reduced with treatment. Less-than-optimal levels of vitamin D are also relatively common in HIV-positive people. Deficiencies of testosterone, reduced muscle mass and perhaps other factors could play a role in thinning bones as well.
The researchers attempted to assess the impact on bone health of anti-HIV drugs that were prescribed for participants' initial treatment. However, due to built-in limitations of the study's retrospective design, researchers cannot draw firm conclusions about the long-term impact of such drugs on the risk of hip fracture.
Size and Strengths
The study is unusual because of its immense size, and this is a great strength. That the researchers compared different groups of people with and without different viral infections is another strength. The study's findings are generally sound -- there is an increased risk for hip fractures among people with HCV infection, including people who are co-infected with HCV and HIV. A previous French study has also found an increased risk for fractures among co-infected people.
Now other research teams need to investigate precisely why HCV is associated with reduced bone mineral density and explore interventions that can improve bone health in people with HCV monoinfection as well as those with HCV-HIV co-infection.
Resources
TreatmentUpdate 189 -- issues related to bone health
"Boning Up on Bone Health" -- The Positive Side
"Good to the Bone" -- The Positive Side
References
Lo Re V 3rd, Volk J, Newcomb CW, et al. Risk of hip fracture associated with hepatitis C virus infection and hepatitis C/human immunodeficiency virus coinfection. Hepatology. 2012 Nov;56(5):1688-98.
Li Vecchi V, Soresi M, Giannitrapani L, et al. Dairy calcium intake and lifestyle risk factors for bone loss in HIV-infected and uninfected Mediterranean subjects. BMC Infectious Diseases. 2012 Aug 15;12:192.
Walker Harris V, Sutcliffe CG, et al. Hip bone geometry in HIV/HCV-co-infected men and healthy controls. Osteoporosis International. 2012 Jun;23(6):1779-87.
Collin F, Duval X, Le Moing V, et al. Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults. AIDS. 2009 May 15;23(8):1021-4.
Grijsen ML, Vrouenraets SM, Wit FW, et al. Low bone mineral density in men who have sex with men regardless of HIV status. Journal of Infectious Diseases. 2012; in press.