Low Bone Mineral Density, Fragility Fracture Risk Increased in HIV Patients

Barbara Boughton

February 23, 2010

February 23, 2010 (San Francisco, California) — Three new studies have highlighted the increased risk for low bone mineral density (BMD) and fragility fractures in those with HIV, researchers announced here at the 17th Conference on Retroviruses and Opportunistic Infections (CROI).

It appears that the increased risk for low BMD is associated with commonly used therapies for HIV. In addition, the risk for fractures might be linked to low CD4 counts and HIV-positive status, investigators told meeting attendees.

In a late-breaking clinical trial presentation, Grace McComsey, MD, from Case Western Reserve University in Cleveland, Ohio, and colleagues studied the effects of 4 different HIV regimens on limb fat and BMD in 269 subjects with HIV. The median age of the study cohort was 38 years.

The AIDS Clinical Trials Group (ACGT) A5224s trial, a substudy of ACTG A5202, is a prospective randomized partially blinded phase 3 trial of abacavir/lamivudine or tenofovir/emtricitabine, combined with either efavirenz or atazanavir/ritonavir, for treatment-naive HIV-positive patients.

Patients were followed for 96 weeks. Results indicated that in all 4 groups, BMD decreased significantly; the most significant changes were seen in the first year of treatment.

Results indicated that those treated with tenofovir/emtricitabine had a significantly larger decline in lumbar spine and overall BMD than those treated with abacavir/lamivudine. Patients who received atazanavir/ritonavir had more significant losses in lumbar spine but not in hip BMD than those who received efavirenz.

"This is important information for clinicians, especially those who treat peri- or postmenopausal women with HIV because it can help them tailor medication regimens," Dr. McComsey told Medscape HIV/AIDS.

In a second study presented at CROI, researchers found an increased risk for fragility fractures in relatively young HIV patients (age range, 25 to 54 years), compared with the general population.

The researchers analyzed data from 5826 HIV patients from the HIV Outpatient Study, an open prospective study that began in 1993 and includes patients from 10 clinics in 8 American cities. Fracture rates between 2002 and 2008 were compared with those recorded during the same time period in the National Hospital Discharge Survey, which includes data from urgent care, emergency care, and inpatient settings.

The researchers found that fracture rates were 4.3 times higher in HIV patients than in the general population, and fragility fractures were also more common. Rates of fracture in HIV patients increased over time.

Among HIV patients, a CD4 count of less than 200 cell/mm3 (hazard ratio [HR], 1.60), comorbid diabetes (HR, 1.62), hepatitis C infection (HR, 1.61), and substance abuse (HR, 1.52) were independently associated with increased fracture risk.

"Future studies need to assess the contribution of both HIV and viremia, as well as antiretroviral therapy, to fracture risk, and the association of bone mineral density to fracture risk among HIV-infected adults," said Christine Dao, MPH, an epidemiologist at the Centers for Disease Control and Prevention in Atlanta, Georgia, and lead author of the study.

A third study presented at CROI of male veterans also found an increased risk for fragility fractures in those with HIV, although the increased risk was "modest," according to lead researcher Julie Womack, PhD, from the Veterans Administration Connecticut Healthcare System in West Haven.

In that study, the researchers analyzed data from the Veterans Aging Cohort Study, a prospective observational cohort, in which HIV-infected men were matched with uninfected veterans from 1997 to 2009.

During the 8-year follow-up, the researchers found an increased prevalence of fragility hip fractures in HIV-infected men, compared with uninfected men. The mean age at fracture was 55 years.

When the researchers evaluated the incidence of hip and vertebral fractures in both the infected and uninfected groups, they found that the increased risk (HR) for fragility fractures among HIV-infected men was 1.53. But when the researchers adjusted for established risk factors for fragility fractures, the increased risk dropped to 1.38.

"While the effect of HIV on fragility fracture risk is modest, it's significant and independent of other variables," Dr. Womack told Medscape HIV/AIDS.

HIV infection in veterans older than 50 years was particularly likely to contribute to increased risk (HR, 1.37; 95% confidence interval, 1.06 - 1.78), she said.

Risk factors other than HIV status were more likely to be linked to increased fracture risk, Dr. Womack said. These factors include cachexia, cerebrovascular disease, race, alcohol use disorder, and older age.

Among those with HIV, the only additional factor associated with increased fragility fracture risk was decreased CD4 count. The researchers' results did not indicate that medications used to treat HIV were associated with increased risk.

Dr. Womack and her fellow researchers concluded that dual-energy x-ray absorptiometry (DXA) scans might not be indicated for patients whose only risk factor is HIV. However, DXA scans might be important for HIV-infected individuals who have multiple clinical risk factors for fragility fractures, such as a history of stroke or cachexia, she said.

"Other studies have shown that fragility fractures are more common in people with HIV," said Dr. McComsey. "Even though the reported increase in fracture risk in the veterans' study was modest, it is increased. And this is a population of men who are at an age when they shouldn't be at increased risk for fractures," she added.

Dr. McComsey, Dr. Womack, and Ms. Dao have disclosed no relevant financial relationships.

17th Conference on Retroviruses and Opportunistic Infections (CROI): Late-breaker abstract 106LB, abstract 128, and abstract 129. Presented February 18, 2010.

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