Low Bone Mass Greater in HIV-Infected Males

Researchers from Children’s Hospital Los Angeles set out to determine why rates of low bone mass seem to be greater in HIV-infected males than in females. The team, led by Grace Aldrovandi, M.D., chief of the Division of Infectious Diseases, studied 11 biomarkers associated with inflammation, bone loss and/or bone formation in about 450 individuals to try to determine causes of this differential bone loss.

As indicated in the March 10, 2016 news release, “Bone loss in HIV infection is due to immune dysregulation, chronic inflammation and antiretroviral therapy, as well as increased bone turnover from the HIV-infection itself. In HIV-infected adults, the combined rates of osteopenia and osteoporosis are as high as 90 percent in men and 60 percent in women, with related fractures 60 percent higher than in the general population.”

“…the researchers discovered that HIV-infected adolescent males had increased levels of sCD14—a marker of macrophage activation. Macrophages are a type of white blood cell critical to the innate immune system. In the bone, macrophages take the form of osteoclasts—the cells responsible for the resorptive processes associated with continuous bone remodeling. Soluble CD14 levels were inversely correlated with measures of bone mineral content and density, suggesting macrophage activation as a possible mechanism for such bone loss.”

“Despite higher levels of general inflammation in HIV-infected females, HIV-positive males in our study showed both lower bone mass and higher sCD14 levels. This is perhaps because estrogen is protective against some of the inflammation seen in chronic HIV, as estrogen represses macrophage function, ” said Dr. Aldrovandi, who is also a professor of pediatrics at the Keck School of Medicine of the University of Southern California.

Dr. Aldrovandi told OTW, “In adults, combined rates of osteopenia and osteoporosis are as high as 90% in men and 60% in women. In large clinical trials of HIV-infected children and adolescents, we noticed that low bone mineral density (BMD) is more pronounced in boys than girls and the difference increases as the adolescent goes through puberty. Additionally, puberty is the time that bone mass normally peaks, so understanding why HIV-infected boys and adolescents develop low bone mineral density is critical so that interventions or therapies can be developed.

“We found two important biomarkers that were elevated more in boys than girls. One of the biomarkers, a biomarker of macrophage activation, was inversely correlated with BMD. In other words, the more macrophage activation a patient had, the more likely they were to have low BMD. This makes sense, in the bone, cells called osteoclasts are derived from macrophages, and osteoclasts are responsible for breaking down bone. Normal growth includes breaking down and laying down bone, but the macrophage activation seen in HIV may tip the scales in favor of more breakdown. So, it appears that macrophage activation is one mechanism responsible for HIV-associated bone loss.”

“We would like to find interventions to decrease macrophage activation in HIV-infected youth and hopefully normalize their BMD.”