PrEP and bone loss in young men

Here’s a piece from Wednesday by Liz Highleyman at hivandhepatitis.com discussing some new findings about PrEP and bone loss among young men. A presentation at the 15th European AIDS Conference (taking place this week in Barcelona) revealed that “young men participating in a pre-exposure prophylaxis (PrEP) demonstration project experienced modest but significant bone loss after starting Truvada.”

Sounds kind of serious, but is this something to be hugely worried about? Is it bad news for advocates of PrEP? Well, no, not really.

Declines in bone mineral density (BMD) are associated with the use of anti-retroviral therapy (ART) to treat HIV infection, including with tenofovir, one of the drugs in the combination pill Truvada that’s used in PrEP. Since little was known about the effect of Truvada on BMD in HIV-negative people when research on PrEP began, researchers have been looking at this issue for many years now.

A paper published earlier this year analysed data from the iPrEx study (the study which first established that PrEP works) and found that taking Truvada was associated with a small but signficant decrease in BMD.

As in this current story, the bone loss was characterised as “significant” which sounds kind of scary, right? But that doesn’t mean that it was clinically significant—that it had any significant health impacts. Rather it means that it was statistically significant. It was a difference that was not the result of chance but a real and measurable change.

That’s important to be clear about because a lot of people see a word like “significant” and assume it means the former instead of the latter. Some people will see a report like this and begin to worry that it means that using PrEP is likely to lead to serious problems with your bones.

In fact, the small decline in BMD was not associated with any serious problems. There was no increase in fractures (the main concern with bone loss) and when Truvada was discontinued the decline largely reversed and BMD returned to previous levels.

The researchers also noted that the “relatively small bone loss associated with [Truvada] is offset by the prevention of HIV infection, which requires combination [antiretroviral therapy] that is associated with relatively greater loss of BMD.” They suggested that people using PrEP should receive information about ways to improve bone health generally, such as doing weight-bearing exercise and making sure they get adequate dietary vitamin D and calcium.

So what does the new report add to this? What’s new here is that the men in this study were young, between ages 18 and 22. Young people typically reach peak bone mass at age 20, so many of the men in this study should have been showing increases in their BMD, not decreases. In the words of the researchers: “Although the BMD losses were generally modest, their occurrence before attainment of peak bone mass in young men who already have low bone mass may increase their risk of fragility in adulthood.”

Because it would take years to observe, there’s no way to know exactly what the long-term impact might be. We may never really be able to firmly link any long-term effects on BMD to the use of Truvada by younger men. So does this mean that young men should not use Truvada as PrEP?

Not necessarily. For one thing, as the researchers in the paper cited above pointed out, the benefit of preventing HIV infection might be worth the risk of a small decline in BMD, particularly since infection with HIV and treatment is associated with even greater losses in BMD.

It does suggest that providers who prescribe PrEP for younger people should pay close attention to bone health. It seems likely that some additional monitoring may be warranted for this age group and will eventually become part of an updated protocol. Certainly people with an existing risk for bone-related problems (young or old) should be aware of this possible side effect of taking Truvada.

One notable finding of this study was that BMD levels were below normal levels in many participants at the start of the study, before they began using Truvada. Apart from any effects of the Truvada those participants would clearly benefit from additional measures (e.g., vitamin D, calcium, exercise) to address that deficiency.

That points out one of the additional benefits of PrEP: it can be a point of entry for people who might otherwise not be getting regular medical care. Overall it might well be of greater benefit for young people at risk of HIV to be using PrEP, remaining HIV-negative, and be monitored for these possible side effects than to be at higher risk of HIV and not be in care at all.

A final aside: PrEP is sometimes described as “the Pill for HIV” and this is another instance where that comparison seems apt. Well, almost. Actually here the comparison is to “the shot” or Depo-Prevera, an injectable contraceptive which can also cause BMD loss. As with PrEP, the impact of the effect on BMD is sometimes exaggerated, and for many women the benefits of this form of contraception outweigh the risks.

I think PrEP should be available as an option for anyone who needs it, but it’s not going to be the right choice for everyone. The important thing is that people are able to make an informed decision based on the facts, that they understand the risks and benefits of whatever prevention approach they choose. The success of PrEP in large part depends on people having confidence in its effectiveness. Just as we emphasise the benefits, we need to frankly acknowledge the limitations and risks of its use as well. That’s not a threat to PrEP’s success, it’s a crucial part of it.

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