Modest Fracture Risk in HIV-Infected Adults

April 25, 2013

By Megan Brooks

NEW YORK (Reuters Health) Apr 25 - HIV-infected adults are at modestly increased risk of fracture, researchers from Columbia University in New York City confirmed in a systematic review and meta-analysis.

In an email to Reuters Health, Dr. Michael T. Yin who worked on the study noted that "many studies have shown that bone density decreases over the first one to two years after starting antiretrovirals but then stabilizes. It is not known whether that short term decrease in bone density increases the risk of fracture. When patients take corticosteroids, their bone density decreases and fracture risk increases over the short term."

To investigate further, Dr. Yin and colleagues searched the literature and found 13 relevant studies on fractures in individuals with and without HIV infection. Nine studies reported all incident fractures and 10 reported incident fragility fractures.

With HIV infection, the pooled incidence rate ratio (IRR) was 1.58 for all fracture and 1.35 for fragility fracture.

In a report online now in the journal AIDS, the investigators say the test for statistical heterogeneity was not significant for the pooled estimate of all fractures; "therefore, the IRR for all fractures appears to be a valid estimate." However, the test for heterogeneity was significant for the pooled risk estimate for fragility fracture "and therefore this IRR should be interpreted with caution."

"It's been known for a while that HIV-infected patients are at increased risk for osteoporosis," Dr. Roger J. Bedimo, from the VA North Texas Health Care System and UT Southwestern Medical Center, Dallas, told Reuters Health. "The question had been whether this translated into increased risk of fragility fractures. With all the caveats of retrospective studies, the data reviewed by Yin et al confirms that this is indeed the case," said Dr. Bedimo, who wasn't involved in the study.

"A second question," he said, "is whether this risk is associated with antiretroviral therapy or not. Initiating antiretroviral therapy consistently leads to a further (but moderate) decline in bone density, but it's unclear whether the antiretroviral drugs increase the fracture risk itself. We've seen increased risk for some drugs but not others. Some data suggest that the fracture risk increases in the first couple of years after initiation of antiretroviral therapy."

Dr. Yin told Reuters Health the studies they reviewed suggest that fracture rates are "higher in the first two years of starting antiretrovirals than the later years (after two years). This could mean starting antiretroviral therapy is associated with a decrease in bone density and weakening of the bone. But this data could also mean that fracture rates are higher in the early phases of antiretroviral therapy because patients are more debilitated, thinner and more likely to fall and fracture. But with longer treatment, their health status improves and (they) are overall less likely to fall and break bones."

Dr. Yin and colleagues also report that smoking, white race, and older age were consistent predictors for fragility fractures. They found it particularly interesting that hepatitis C virus (HCV) was consistently identified as an independent risk factor for both fragility and non-fragility incident fractures. The increased risk of fracture was approximately 1.5-2 times greater in HIV/HCV co-infected than HIV mono-infected individuals.

"Although the mechanisms are not well understood, HIV/HCV coinfection appears to have a negative effect on bone strength and fracture risk. The relationship between HIV/HCV co-infection and fracture risk warrants further study," the investigators say.

While the overall increase in risk of fracture seems modest, "this can be expected to increase in the future as the HIV-infected population continues to age, and studies of risk reduction interventions are warranted," they conclude.

What's the best way to mitigate the risk of fractures in HIV patients? "The first answer would be increased awareness among providers," Dr. Bedimo said. "Guidelines for primary and secondary prevention of fracture in HIV-infected patients have been published."

It's also appropriate, he said, to "measure bone mineral density in every patient over the age of 50, post-menopausal or following fractures likely to be osteoporotic in nature (hip, wrist, vertebra). Use the information to calculate the fracture risk. There's an online tool for that: Decisions on supplementation (calcium, vitamin D) or other therapeutic interventions depend on the findings."

"It is very likely that some of the strongest predictors of increased fracture risk are low body mass index and co-infection with hepatitis C with or without significant liver disease. More attention might need to be paid to these patients. Ultimately there will need to be prospective studies looking at whether different antiretroviral treatment regimens with or without osteoporosis medications," Dr. Bedimo said.

The study was supported by investigator grants. Dr. Yin has served as a consultant for Gilead Sciences and Abbott Laboratories. No other potential conflicts of interest were noted.


AIDS 2013.