HIV/HCV co-infection associated with increased risk of osteoporosis and fractures

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Co-infection with HIV and hepatitis C virus (HCV) is associated with increased risks of low bone mineral density (BMD) and fracture, investigators report in the online edition of AIDS. Results of 15 separate studies showed that people living with co-infection had a higher risk of osteoporosis than people with HIV-mono-infection, and that fracture incidence was higher among people with co-infection compared to both people with HIV-mono-infection and healthy controls. The authors believe their findings underline the importance of monitoring bone mineral density in all older people with co-infection.

“Our review found that HIV/HCV-co-infected individuals have a modestly increased risk of osteoporosis and fractures compared with HIV-mono-infected controls, and substantially higher risk than uninfected controls,” comment the researchers.

Chronic hepatitis C is associated with an increased risk of osteoporosis. HIV infection and antiretroviral therapy have also been associated with an increased risk of low bone mineral density and fractures. Large numbers of people are living with HIV and HCV co-infection. A team of US investigators therefore wanted to see if people with co-infection had an increased risk of osteoporosis and fractures compared to people with HIV-mono-infection and people with neither infection (healthy controls).



Bone disease characterised by a decrease in bone mineral density and bone mass, resulting in an increased risk of fracture (a broken bone).

bone mineral density (BMD)

The higher your bone mineral content, the denser your bones are. And the denser your bones, the stronger they are and the less likely they are to break. A bone density test uses X-rays to measure how many grams of calcium and other bone minerals are packed into a segment of bone. The bones that are most commonly tested are in the spine, hip and sometimes the forearm. 

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.

systematic review

A review of the findings of all studies which relate to a particular research question and which conform to pre-determined selection criteria. 


A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

They therefore conducted a systematic review and meta-analysis of studies published or presented at major conferences before 2013 that compared these outcomes between people with co-infection, people with HIV-mono-infection and healthy controls.

A total of 15 studies were eligible for inclusion: nine provided data on osteoporosis and six reported on fracture risk. The studies were conducted in the US, Europe and Taiwan. Four studies included women only and one included only men. Sample size varied from 22 post-menopausal women to approximately 37,000 people receiving care in the US.

Prevalence of osteoporosis in people with co-infection ranged from 5-45%. The pooled estimate was 22%. Co-infection was associated with a significantly increased risk of low bone mineral density compared to HIV mono-infection (OR = 1.63; 95% CI, 1.27-2.11). The risk was little altered after the authors excluded the study with post-menopausal women (overall prevalence= 20%; OR = 1.61; 95% CI, 1.23-2.12).

Co-infection was also associated with an increased fracture incidence. The risk was significantly increased when people with co-infection and people with HIV-mono-infection were compared (IRR = 1.77; 95% CI, 1.44-2.18). People with co-infected also had a significantly higher incidence of fragility fractures compared to people with HIV-mono-infection (IRR = 1.70; 95% CI, 1.18-2.43). Moreover, fracture incidence was substantially higher among people with co-infection when compared to people in the control group (IRR = 2.95; 95% CI, 2.17-4.01).

Factors independently associated with an increased risk of osteoporosis were HIV/HCV co-infection, older age, lower BMI (body mass index), post-menopausal status and longer duration of therapy with an HIV protease inhibitor. Smoking, low physical activity and methadone use were identified as risk factors in some studies.

Risk factors for fracture included co-infection, older age, smoking, white ethnicity, alcohol and substance abuse, diabetes and low BMI. Some studies also found that injecting drug use or opioid therapy, hormone replacement therapy or oral contraception, kidney function, menopause and peripheral neuropathy were also risk factors. In multivariate analysis, co-infection, older age, white ethnicity, alcohol and substance abuse, kidney function and diabetes all remained associated with a significant increase in the risk of fracture.

“This systematic review and meta-analysis suggests an increase in osteoporosis in HIV/HCV-co-infected individuals,” comment the authors. “HIV/HCV-co-infection is also associated with a pooled fracture IRR of 1.77 when compared with HIV mono-infection, with higher IRR values for traumatic fractures.”

They conclude their findings “confirm the importance of risk modification and DXA screening at age 50 for prevention of osteoporosis and fractures in HIV/HCV-co-infected individuals.”


Dong HV et al. Osteoporosis and fractures in HIV/hepatitis C virus coinfection: a systematic review and meta-analysis. AIDS 28, online edition. DOI: 10. 1097/QAD.0000000000000363, 2014.