March/April 2016 

Large study looks at risk factors for bone problems in HIV

Multiple studies have found that HIV-positive people are at increased risk for developing osteopenia and osteoporosis (thinner-than-normal bones) and, in rare cases, osteonecrosis (the degeneration and death of bones, particularly joints). These complications increase the risk for fractures.

Researchers with a large database called EuroSIDA reviewed the health-related data that they had accumulated since 2004. They focused on 11,820 HIV-positive participants who had been monitored for an average of seven years. When it came to fractures and osteonecrosis, the following had occurred:

  • 416 people developed 619 new fractures
  • 73 people developed 89 new instances of osteonecrosis

Common locations of fractures were as follows:

  • arms
  • ribs
  • feet

An immunological link

In general, the risk of a fracture was greatest among participants with a CD4+ count of 200 cells/mm3 or less. Fracture risk was much lower among people with a CD4+ count between 501 and 750 cells/mm3 and lowest among people whose CD4+ count was greater than 750 cells/mm3.

There was no similar trend between CD4+ cell counts and the risk of osteonecrosis.

Risk factors for fractures

Among the 619 new fractures, the risk factors that researchers uncovered were as follows:

  • older age
  • less-than-ideal body weight
  • injecting street drugs
  • hepatitis C virus co-infection
  • prior diagnosis of osteonecrosis and fractures
  • recent (in the past 12 months) diagnosis of cancer unrelated to AIDS
  • recent (in the past 12 months) diagnosis of cardiovascular disease

People who entered the EuroSIDA study with relatively high CD4+ cell counts and people of colour had a significantly reduced risk for developing osteoporosis-related fractures.

Risk factors for osteonecrosis

Among the 89 new instances of osteonecrosis, some of the risk factors that researchers found were as follows:

  • prior diagnosis of osteonecrosis
  • prior fractures
  • prior AIDS
  • prior AIDS-related cancer

As with the previous analysis of fractures, the EuroSIDA researchers found that people of colour had a reduced risk for osteonecrosis.

The possible role of tenofovir

The current and widely used formulation of tenofovir (tenofovir disoproxil fumarate, TDF) which is in Truvada and several other medicines has been associated with an increased risk for bone problems.

A new formulation of tenofovir called TAF (tenofovir alafenamide) is gradually being introduced in high-income countries. It appears to be safer for bones (and kidneys).

In the EuroSIDA study, if participants used tenofovir, it would have been the older formulation.

Overall, researchers found that people who had been exposed to tenofovir had an increased risk for bone fractures. This risk was elevated in the first year of use. If people continued to use the drug, the risk of developing a fracture remained elevated but stable; that is, it did not significantly increase further.

Bear in mind

There are many factors that reduce the density of bone (and/or increase the risk for bone-related problems), such as the following:

  • tobacco smoking
  • excessive intake of alcohol
  • use of corticosteroids

These factors were not analysed in the present study, perhaps because researchers did not have sufficient information on them.

EuroSIDA is an observational study and so it cannot prove a link between “cause and effect.” That is, the study cannot prove that what it identified as a risk factor did indeed cause the problems it was assessing. However, other studies have found broadly similar findings to the EuroSIDA study and so the results from this study are likely correct.

The researchers presented their findings at the Conference on Retroviruses and Opportunistic Infections. They barely had 10 minutes to do so (this time limit is often standard at most high-level international scientific conferences) and did not explain the context of some of their findings. For instance, the link between osteonecrosis and the diagnosis of a life-threatening infection or cancer that is the hallmark of AIDS may have arisen because patients with these conditions sometimes experience intense inflammatory reactions that require potent doses of anti-inflammatory drugs, such as corticosteroids. These drugs have been previously linked to the development of thinning bones. It is also possible that if patients were sufficiently ill to develop AIDS, they may have had untreated HIV infection for a long time. During that time they could have had malabsorption, been underweight and experienced excessive activation and inflammation of their immune system. In theory, all of these factors could have affected their bone density over time.

The link between fractures and a recent diagnosis of cardiovascular disease is interesting and should be further explored in other analyses.

—Sean R. Hosein


Borges AH, Hoy J, Florence E, et al. Antiretrovirals, fractures, and osteonecrosis in a large European HIV cohort. Conference on Retroviruses and Opportunistic Infections, 22-25 February 2016, Boston, MA. Abstract 46.