Low bone mineral density common in HIV-positive men

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A large proportion of HIV-positive men have low bone mineral density, Australian researchers report in the December 1st edition of the Journal of Infectious Diseases. Treatment with a boosted protease inhibitor was identified as a risk factor, and the investigators suggest that their results point to tenofovir also causing changes in the bone metabolism. The risk of fractures was sufficiently high in 16% of patients to warrant treatment.

There has been considerable debate about the causes of low bone mineral density in patients with HIV. The virus itself has been identified as a risk factor, but so too has treatment with antiretroviral drugs. Most of the men in the study had well controlled HIV disease, prompting the investigators to comment “it is difficult to conclude that HIV replication and disease severity are important contributors to the observed low bone mineral density in our population.”

The study involved 153 HIV-positive adults who received routine HIV care at St Vincent’s Hospital, Sydney, in 2007. Most (98%) were men, the median age being 48 years. Viral load was undetectable in 83% of patients and median CD4 cell count was normal, being over 500 cells/mm3.

Glossary

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. 

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

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.

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

osteoporosis

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

Information was gathered by the investigators on well-established risk factors for bone problems in patients with HIV, such as body weight, body mass index, smoking and duration of HIV infection.

Investigators therefore gathered information on current and past antiretroviral therapy. Treatment with boosted protease inhibitors and tenofovir (Viread, also in the combination pills Truvada and Atripla) have also been associated with low bone mineral density. Furthermore, tenofovir treatment has been implicated in kidney dysfunction, which can affect the bone metabolism.

Bone mineral density was assessed using DEXA scans.

Low bone mineral density was present in 42% of patients, with 4% having osteoporosis.

Kidney dysfunction was diagnosed in 7% of patients. This was associated with longer duration of HIV infection (p < 0.006), longer duration of treatment with tenofovir (p = 0.019), therapy with a boosted protease inhibitor (p = 0.009) and lower body mass index (p = 0.046).

The investigators then explored risk factors for low bone density. They found that the following were protective against this: higher body mass index, higher testosterone levels, and higher creatinine clearance.

However, treatment with a boosted protease inhibitor was significantly associated with low bone density (p = 0.006).

After controlling for potential confounding factors, the investigators found that higher testosterone remained protective against low bone mineral density (p = 0.027), whereas therapy with a boosted protease inhibitor was still associated with lower bone density (p = 0.011).

The investigators were surprised by their finding that tenofovir did not cause reductions in bone density. They suggest that a possible explanation for this could be the relatively short duration of treatment with the drug (average, two years). Moreover, they found that there were subtle changes in the bone metabolism of patients taking tenofovir, suggesting that therapy with the drug could result in bone loss.

Finally, the researchers looked at the potential implications of low bone mineral density for their patients. They used an established tool to estimate the ten year fracture risk (World Health Organization FRAX equation).

Overall, the ten year risk for the whole cohort was 1.2% for a hip fracture and 5% for a fracture related to osteoporosis.

Moreover, 16% had a ten year risk of fracture above 7.5%, the threshold at which treatment with bisphosphonate is considered cost effective.

“We found a high prevalence of low bone mineral density in HIV-infected adults receiving combination antiretroviral therapy, particularly in those receiving a boosted protease inhibitor”, conclude the investigators. They add “the use of a tool such as the WHO FRAX tool warrants further validation in studies in HIV-infected patients.”

References

Calmy A et al. Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study. J Infect Dis 200: 1746-54, 2009.