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Low CD4 Count Linked to Bone Fractures


A large Australian study found HIV positive people with lower CD4 T-cell counts were at greater risk of fractures due to bone loss.

A growing body of evidence indicates that people with HIV are more likely to have low bone mineral density, though it is not clear whether this is related to HIV infection itself, resulting inflammation, antiretroviral drugs, or a combination of these and other factors. Bone loss (osteopenia, or the more severe osteoporosis) can lead to fragility fractures, that is, bone breaks not due to trauma.

As described in the April 23, 2011, advance online edition of Journal of Acquired Immune Deficiency Syndromes, Michelle Yong and colleagues looked at the incidence, prevalence, and risk factors for development of low-trauma fragility fractures in people with HIV.

In this case-control study the researchers retrospectively analyzed medical records from more than 2400 HIV positive patients seen at the Alfred Hospital in Melbourne between 1998 and 2009. Each person who sustained fracture(s) was matched with 2 control patients of the same sex, age, and duration of HIV infection. Most participants (89%) were men, most were white, and the mean age was about 50 years.


  • 61 patients sustained a total of 73 low-trauma fractures.
  • The overall fracture incidence rate was 0.53 per 100 person years, with a period prevalence of 3.34 per 100 patients.
  • More than half of the fractures occurred in patients under 50 years of age.
  • In a multivariate analysis controlling for other factors including age, race, and weight, independent risk factors for fragility fractures included:
  • CD4 cell count < 200 cells/mm3 (odds ratio [OR] 4.91, or nearly 5-fold higher risk);
  • Use of corticosteroid drugs (OR 8.96, or about 9 times higher risk);
  • Use of anti-epileptic medications (OR 8.88).
  • There were no significant associations, however, between fracture risk and detectable HIV viral load, ART use, or antiretroviral drug class.
  • 88% of patients who sustained fractures had established osteopenia (32 people) or osteoporosis (56 people).

"This is the largest clinical study to date of fragility fractures occurring in an HIV infected population," the investigators concluded. "The study found that risk of fracture was strongly associated with a low CD4 cell count, use of corticosteroids and anti-epileptic medications. There were no associations between fracture risk and viral load, use of, class, or duration of antiretroviral agent."

"This study is the first to report an association between low CD4 cell count and increased risk of fragility fracture," they elaborated in their discussion. Prior research has shown a link between bone problems and nadir or lowest-ever CD4 count before starting ART. This may also be the case for people who do not achieve good CD4 cell recovery after starting therapy.

"One possible mechanism may be that patients with poor immunological recovery have persistently up-regulated pro-inflammatory cytokines making them susceptible to fracture," the study authors hypothesized.

"Dysregulated bone metabolism has also been seen in patients with advanced HIV disease," they added, but "[t]his study did not demonstrate a corresponding increased risk of fracture with detectable viral load > 400 copies/mL suggesting that those at risk are not necessarily the same as those with untreated/poorly controlled HIV infection."

Just 44% of patients had received DEXA bone scans, "suggesting a lack of appreciation, or under investigation of bone disease by those managing HIV patients," they noted. "The number of patients tested for vitamin D levels would also be of interest as this is a potential reversible contributor of low bone mineral density."

Investigator affiliations: Department of Infectious Diseases, The Alfred Hospital, Melbourne, Australia; Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia.


MK Yong, JH Elliott, IJ Woolley, and JF Hoy. Low CD4 Count is Associated with an Increased Risk of Fragility Fracture in HIV-infected Patients. Journal of Acquired Immune Deficiency Syndromes (abstract). April 23, 2011 (Epub ahead of print).