Women with HIV co-infected with hepatitis B or C have increased risk of bone problems

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HIV-positive women who are co-infected with hepatitis B or hepatitis C have lower bone mineral density than HIV-positive women who do not have these co-infections, Italian investigators report in the October edition of AIDS.

This difference was not, however, present in men, with bone mineral density being broadly comparable between HIV and hepatitis co-infected men and HIV mono-infected men.

The investigators are calling for further studies to “elucidate the mechanism for low bone mineral density in coinfected women.”

Glossary

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. 

confounding

Confounding exists if the true association between one factor (Factor A) and an outcome is obscured because there is a second factor (Factor B) which is associated with both Factor A and the outcome. Confounding is often a problem in observational studies when the characteristics of people in one group differ from the characteristics of people in another group. When confounding factors are known they can be measured and controlled for (see ‘multivariable analysis’), but some confounding factors are likely to be unknown or unmeasured. This can lead to biased results. Confounding is not usually a problem in randomised controlled trials. 

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

prognosis

The prospect of survival and/or recovery from a disease as anticipated from the usual course of that disease or indicated by the characteristics of the patient.

dual energy x-ray absorptiometry scan (DXA or DEXA)

A test that uses low-dose x-rays to measure bone mineral density, including calcium content, in a section of bone. They are used to detect osteoporosis and predict the risk of bone fracture. 

Antiretroviral therapy has brought about significant improvements in the prognosis of HIV-infected individuals and there is now optimism that such treatment will provide patients with HIV with the opportunity to live a normal lifespan.

However, studies have consistently shown that co-infection with hepatitis B, hepatitis C, is associated with higher rates of serious illness and death in patients with HIV.

Unsurprisingly, most of the research into the impact of hepatitis co-infection in individuals with HIV has focused on liver disease. However, both hepatitis B and C can cause other serious health complications, one of which is reduced bone mineral density.

Investigators from Modena, Italy, therefore conducted a cross-sectional (or 'snap-shot') study to determine the prevalence and risk factors for reduced bone mineral density in patients with HIV who also had co-infection with hepatitis B or C.

Bone mineral density was assessed using DEXA scans of two sites, the lumbar spine and the femoral neck. The investigators calculated the age and sex-specific Z score – the difference in bone mineral density from that expected for an individuals age and sex – and a Z score of at least –2.0 was taken as indicating significantly lower-than-expected bone density.

Blood samples were also obtained to assess HIV viral load, CD4 cell count and to measure metabolic parameters than can affect bone mineral density.

Conducted between 2004 and 2007, the study involved 1237 patients. Antibodies to hepatitis B were detected in 85 (9%) individuals and antibodies to hepatitis C in 572 (47%).

A significant relationship was found between hepatitis co-infected, sex and bone mineral density in both the lumbar spine (p = 0.002) and femoral neck (p = 0.04). Therefore, the investigators analysed all their results according to sex.

Men had generally lower Z scores than women for the lumbar spine (–0.5 vs + 0.06, p Z scores than HIV mono-infected women for bone mineral density in this region (–0.15 vs + 0.29, p

By contrast, there were no significant differences in bone mineral density in the lumbar spine region between co-infected and mono-infected men.

Next the investigators looked differences in femoral neck bone mineral density Z scores. Once again, co-infected women had lower Z scores than mono-infected women, even after adjusting for possible confounding factors (difference, –0.26, p = 0.02).

However, femoral neck bone density Z scores were comparable for co-infected and mono-infected men.

The investigators also conducted analyses to see if the risk of low bone mineral density differed for individuals co-infected with HIV and hepatitis C and those only infected with HIV.

Twice as many women as men (8% vs 4%, p Z score of –0.2 or less.

Furthermore, low lumbar spine bone mineral density was more common in co-infected patients than mono-infected individuals (9% vs 6%).

After adjustment for factors such as use of antiretroviral therapy, smoking, and levels of physical activity, the investigators found that the risk of low bone mineral density in this region was higher for co-infected women than co-infected men.

Low bone mineral density in the femoral neck was slightly more prevalent amongst women than men (8% vs 7%). Z scores of –0.2 or less were also more common in co-infected patients (9% vs 7%), but this difference was not significant.

After adjustment for confounding factors, the investigators once again found that the risk of reduced bone mineral density in this region was increased for co-infected women but not co-infected men. But the association was weak and did not achieve significance.

Finally, the investigators looked at lumbar spine and femoral neck scores together. This showed that low Z scores in these sites were more common in women than men (14% vs 9%, p Z scores in these regions persisted for women (adjusted OR, 2.89, 95% CI, 1.31 to 6.29), but not for co-infected men.

Focusing on individuals co-infected with hepatitis C, they found that bone mineral density Z scores were significantly lower in both sites for co-infected women (adjusted OR, 2.99; 95% CI, 1.33 to 6.74), but once again this was not the case for co-infected men.

“We found that viral hepatitis increased the risk of low bone mineral density among HIV-infected patients”, comment the investigators. They note that the reasons why this association was significant in co-infected women “remain unclear”, but they state that much is still unclear about the impact of hepatitis B or C co-infection on bone metabolism.

“Future studies should evaluate fracture rates and examine risk factors and potential mechanisms for low bone mass among HIV/viral hepatitis-coinfected patients,” conclude the authors.

References

Lo Re V et al. Viral hepatitis is associated with reduced bone mineral density in HIV-infected women but not men. AIDS 23: 2191-98, 2009.