Low CD4 increases risk of fragility fractures for patients with HIV

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A low CD4 cell count is associated with an increased risk of fragility fractures in patients with HIV, an Australian study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes shows.

The retrospective, case-controlled study involved 2424 patients who received care at the Alfred Hospital, Melbourne, between 1998 and 2009.

After adjustment for potential confounders, only a CD4 cell count below 200 cells/mm3, use of corticosteroids, and treatment with anti-epileptic drugs were significantly associated with an increased risk of fragility fractures. There was no relationship between fractures and HIV therapy or the use of any individual anti-HIV drugs. Nor did  the level of viral load have a significant association.


retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

bone mineral density (BMD)

The higher your bone mineral content, the denser your bones are. And the denser your bones, the stronger they are and the less likely they are to break. A bone density test uses X-rays to measure how many grams of calcium and other bone minerals are packed into a segment of bone. The bones that are most commonly tested are in the spine, hip and sometimes the forearm. 


Bone disease characterised by a decrease in bone mineral density and bone mass, resulting in an increased risk of fracture (a broken bone).

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.


A condition in which bone mineral density is lower than normal, but less severe than osteoporosis.

“This is the first study to report an association between low CD4 cell count and increased risk of fragility fracture,” comment the investigators. “One possible mechanism may be that patients with poor immunological recovery have persistently upregulated proinflammatory cytokines which makes them susceptible to fracture.”

Low bone mineral density is increasingly recognised as a problem for patients with HIV. The exact causes are unclear, but may include the effects of HIV, immune suppression, low vitamin D levels, or the side-effects of antiretroviral drugs and other treatments.

The clinical significance of altered bone metabolism is also unclear. Studies examining fracture rates in HIV-positive patients have produced conflicting results.

To clarify these issues investigators in Australia undertook a retrospective study involving patients who received care in the era of combination antiretroviral therapy.

Data were gathered on the incidence and prevalence of fragility fractures.

In addition, patients who experienced fractures were matched with two controls of the same gender and similar age. This allowed the investigators to analyse the risk factors for fragility fractures.

A total of 94 fractures were recorded in 81 patients. This provided an incidence rate of 0.53 per 100 person years, and the overall prevalence of fractures during the eleven years of the study was a little over 3%.

However, the investigators excluded 21 fractures that were caused by high trauma events such as car crashes or assault. This left 73 low trauma or fragility fractures which were included in their analyses.

The mean age at the time of fracture was 50 years. Most of the fractures (58%) occurred in patients aged under 50, including 20% which occurred in individuals aged under 40. Most of the patients were male (89%), of Caucasian background (92%), and had been living with diagnosed HIV infection for a little over eleven years.

Common fracture sites were the vertebrae (25%), neck of the femur (21%) and wrist (18%).

Body mass index (BMI) was available for 68% of participants, and was lower for patients who experienced fractures than the controls (22.5 vs. 22 kg/m2, p = 0.001). Moreover, fracture patients were significantly more likely to be underweight, defined as under 20 kg/m2, than controls (27% vs. 11%).

Individuals who experienced a fracture had a significantly lower median CD4 cell count than control patients (283 vs. 448 cells/mm3, p = 0.0003). However, viral load was broadly comparable (112 vs. 50 copies/ml).

Results of DEXA scans were available for 56% of fracture patients and 30% of controls. These showed that 88% of fracture patients had low bone mineral density, with 32% having osteopenia and 56% osteoporosis. Low bone mineral density was also present in 55% of control patients (44% osteopenia; 11% osteoporosis).

After taking into consideration potentially confounding factors, the investigators found a significant relationship between a CD4 cell count below 200 cells/mm3 and increased risk of fracture (odds ratio [OR] = 4.91; 95% CI, 1.78-13.57, p = 0.002).

Treatment with a corticosteroid also increased the risk of fracture (OR = 8.96; 95% CI, 1.55-51.88, p = 0.014).  “Steroid therapy was commonly prescribed as adjuvant therapy in treating HIV specific illnesses,” explain the investigators.

There was also a significant relationship between treatment with anti-epileptics and fracture risk (OR = 8.88; 95% CI, 1.75-44.97, p = 0.008). The investigators note that these drugs “were frequently prescribed for indications such as peripheral neuropathy, mood disorders, chronic pain syndrome, and post-hepatic neuralgia.”

No relationship was detected between fracture risk and HIV therapy or treatment with any specific anti-HIV drug. However, the investigators caution, “it is possible that there were too few cases to determine a true association…and a larger study is required.”

They also note that the findings of their study are limited by the retrospective design.

Nevertheless they conclude that the risk of fracture “was independently associated with a low CD4 cell count, use of corticosteroids or anti-epileptic medications. There were no associations between fracture risk and use of, class or duration of antiretroviral agent.”


Yong MK et al. Low CD4 count is associated with an increased risk of fragility fracture in HIV-infected patients. J Acqir Immune Defic Synr, online edition: doi: 10.1097/QAI.0b013e31821ecf4c, 2011 (click here for the free abstract).