Italian Study Links Hepatitis B or C Coinfection with Bone Loss in HIV Positive Women but not Men

HIV positive women -- but not men -- with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection were more likely to have reduced bone mineral density than women with HIV alone, according to a study published in the October 23, 2009 issue of AIDS.

By Liz Highleyman

Bone loss (osteopenia, or its more severe form, osteoporosis) is common among people with HIV. To date, it is not fully understood whether this is due to HIV infection itself, antiretroviral therapy (ART), systemic inflammation, the normal aging process as HIV positive people live longer, or some combination of these and possibly other factors. Low bone mineral density can lead to fractures and has been linked to increased mortality.

Like HIV, hepatitis C has been linked to bone loss in some prior studies; less is known about the effect of hepatitis B, or the combined effects of HIV and viral hepatitis, on bone health.

Vincent Lo Re from the University of Pennsylvania School of Medicine and colleagues sought to determine whether viral hepatitis is an independent risk factor for low BMD in HIV positive individuals.

This cross-sectional study included 1237 HIV patients enrolled in the Modena HIV Metabolic Clinic Cohort in Italy. Of these participants, 625 were coinfected with HBV (85 patients, 9%) or HCV (572 patients, 47%); 5% had both hepatitis viruses.

As a group, coinfected participants had lower body mass index, longer median duration of HIV infection, and lower current and nadir (lowest-ever) CD4 cell counts. In addition, the coinfected patients were less likely to be physically active, more likely to smoke cigarettes, and had lower serum 25-hydroxyvitamin D levels -- all risk factors for bone loss -- but were less likely to drink alcohol.

The researchers used dual-energy X-ray absorptiometry (DEXA) scans to measure bone density of the lumbar spine and femoral neck (the narrow part of the femur, or thigh bone, where it connects to the pelvis at the hip joint). They also collected data on clinical symptoms, HBV and HCV status, and biomarkers of bone metabolism. Multivariate regression analysis was used to assess the association between viral hepatitis and low BMD, defined as a Z-score of -2.0 or less at the lumbar spine, femoral neck, or both.

Results

	Mean BMD Z-scores were significantly lower among HIV positive women with viral hepatitis compared with HIV monoinfected women at both sites:
	- Lumbar spine: -0.15 vs +0.29; difference -0.44 (P < 0.001); - Femoral neck: -0.64 versus -0.39; difference -0.25 (P = 0.009).
	However, no significant differences in mean BMD Z-scores were observed between HIV/HBV or HIV/HCV coinfected men and HIV monoinfected men at either site.
	After adjusting for age, body weight, physical activity, smoking, duration of HIV infection, and ART use, viral hepatitis was independently associated with low BMD among women (adjusted odds ratio [OR] 2.87) but not among men (adjusted OR 1.19).
	Coinfected women had a lower median concentration of parathyroid hormone -- which promotes release of calcium from bone -- compared with HIV monoinfected women (60.1 vs 68.1 pg/mL, respectively; P = 0.02).
	However, median levels of 2 other substances that play a role in bone metabolism -- 25-hydroxyvitamin D (19.1 vs 19.6 ng/mL; P = 0.6) and osteocalcin (3.0 vs 3.2 ng/mL; P = 0.8) -- were similar in coinfected and monoinfected women.
	Among men, too, coinfected patients had lower parathyroid hormone concentrations but similar 25-hydroxyvitamin D and octeocalcin levels compared with HIV monoinfected men.

Based on these findings, the study authors concluded, "Viral hepatitis was associated with a higher risk of low BMD among HIV-infected women but not men."

It is not clear what mechanism(s) could explain a link between HBV or HCV coinfection in women but not men. Prior research has shown that HIV positive men, and men with HCV monoinfection, experience faster and greater bone loss than healthy men without either of these infections. In this study, men had significantly lower overall mean Z-scores than women at the lumbar spine (-0.50 vs +0.06) and the femoral neck (-0.68 vs -0.52), though they did not show the same association with viral hepatitis.

"To elucidate the mechanisms for low BMD in coinfected women, future studies should evaluate serum levels of cytokines, markers of bone resorption, insulin-like growth factor-1, osteoprotegerin, estradiol, testosterone, follicle-stimulating hormone, and sex hormone-binding globulin," the researchers recommended.

Division of Infectious Diseases, Department of Medicine, and Center for Clinical Epidemiology & Biostatistics, and Division of Nephrology, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA; Infectious Diseases Clinic and Unit of Endocrinology and Metabolism, University of Modena and Reggio Emilia, Modena, Italy.

10/20/09

Reference
V Lo Re, G Guaraldi, M Leonard, and others. Viral hepatitis is associated with reduced bone mineral density in HIV-infected women but not men. AIDS 23(16): 2191-2198. October 23, 2009. (Abstract).