06:54am Tuesday 21 November 2017

HIV Components Drive Bone Breakdown, Even without Active Infection

News Article ImageThe intersection of aging and HIV infection appears to have a destructive impact on bone health. Researchers at Emory University School of Medicine have shown in an animal model that the presence of HIV proteins, even without a replicating virus, leads to alterations in cells that break down bone.

Trabecular bone in wild-type (WT) and HIV-1 transgenic rat femurs, seen by CT scanning. View enlarged image.

The team’s results were published this week online in the Early Edition of the Proceedings of the National Academy of Sciences.

“We found that HIV proteins, by themselves, can alter the output of hormones that affect the balance between bone formation and bone breakdown leading to bone loss,” says senior author M. Neale Weitzmann, MD, assistant professor of endocrinology at Emory University School of Medicine. “This information could help doctors decide the best way to stave off osteoporosis and bone fractures, which are becoming increasingly common in individuals living with HIV infection.”

Collaborating authors are David Guidot, MD, director of the Division of Pulmonary, Allergy and Critical Care Medicine at Emory and director of the Emory Alcohol and Lung Biology Center; and Igho Ofotokun, MD, assistant professor of medicine (infectious diseases).

The Emory team studied rats that have an HIV virus that cannot replicate incorporated into their DNA. The virus does not kill white blood cells directly as it does in human patients, but parts of the virus appear in the rats’ blood, and appear to distort the function of immune cells.

Compared to normal rats, the HIV-transgenic rats’ bone mineral density (determined by X-rays) in the femur was reduced by 36 percent, while the proportion of bone in the trabecular (spongy) areas of their femurs was reduced by 32 percent.

Some of the reduction in bone mass may be because the HIV-transgenic rats weigh 21 percent less, but they also have more osteoclasts– cells that originate in the bone marrow that break down bone. The authors found that in the HIV-transgenic rats, B cells (a variety of immune cells) produce more of certain hormones that promote osteoclast differentiation. For instance, their B cells produce more RANKL, a key osteoclast promoting factor and the target of an anti-osteoporosis drug called denosumab, and less osteoprotegerin, an osteoclast inhibitor, Weitzmann says.

Previous studies have shown that viral infection drives changes in the balance of the types of B cells present in HIV-infected people. Weitzmann says the next step in the team’s research will be to examine B cell subpopulations in HIV-infected people, and to measure their output of hormones involved in bone growth and breakdown.

The research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Allergy and Infectious Diseases and the Department of Veterans Affairs.

Reference:
T. Vikulina et al. Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats. PNAS Early Edition (2010).

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The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children’s Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital.  The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.


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