Study Finds Lower Than Expected Bone Density Loss in Regular PrEP Users

A slight loss in bone mineral density (BMD) can occur with the use of tenofovir‐containing pre-exposure prophylaxis (PrEP) for HIV prevention. Although this bone density loss is reversible with PrEP discontinuation, a new study has examined the relationship between PrEP adherence and BMD loss.

Daily PrEP use is key to preventing HIV in high-risk individuals, though factors such as sexual risk behavior and partnership type can lead to varying PrEP adherence. In a study published online in the journal AIDS Research and Human Retroviruses, investigators analyzed data from a bone and metabolic sub-study of an open‐label PrEP demonstration project conducted among MSM and transgender women. The paper notes that declines in BMD have been varied in prior PrEP demonstration projects, which may be related to variations in adherence, and that no previous study has proven that intermittent PrEP use decreases the risk of bone loss or renal‐related toxicity.

“As a clinician, what I really want to know is what the expected toxicity of a treatment might be if someone took the treatment every day. In randomized controlled trials of PrEP, adherence was actually quite variable,” study author Matthew Spinelli, MD, told Contagion®. “To overcome this issue, we leveraged adherence benchmarks established for tenofovir-diphosphate in dried blood spots to model what impact PrEP would have on bone density with near-perfect daily adherence.”

There were 290 participants enrolled in the bone and metabolic sub-study from 7 sites in Cape Town, South Africa; Chiang Mai, Thailand; Lima, Peru; Rio de Janeiro, Brazil; and San Francisco and Chicago. Participants in the sub-study underwent dual X‐ray absorptiometry to determine BMD at the hip and lumbar spine at enrollment and every 24 weeks until the end of their study participation. Investigators found a monotonic decrease in BMD with higher weekly PrEP adherence, observing a drop in spine BMD of only approximately 1% and a 0.5% decrease in hip BMD among PrEP users with very high adherence over a median of 24 weeks.

“Because we specifically sought to model the impact on bone density in those with daily adherence, we worried that we might find higher than previously reported bone density declines,” explained Spinelli. “Instead we found quite subtle impact of daily PrEP use on bone density in this sub-study, which was reassuring.”

For those with high risk of bone fracture, such as older adults, who are planning on initiating prolonged daily PrEP, the study authors recommend considering alternate PrEP strategies, such as tenofovir alafenamide‐based PrEP once available. In addition, they write that dose‐limiting strategies such as intermittent PrEP use could potentially reduce the risk of bone density loss, although additional research is needed to compare toxicity in daily versus intermittent PrEP use. Based on the study’s findings of only modest BMD declines seen even with very high PrEP adherence, the differences are likely only clinically significant only for individuals at highest risk of bone toxicity.

On whether supplements may help PrEP users offset the bone toxicities of HIV prophylaxis drugs, Spinelli says it’s a question worth researching. “PrEP users, at least in my experience, are not given a recommendation for calcium and vitamin D prior to starting PrEP. This is an idea that deserves additional study in a randomized controlled trial.”