Zoledronic Acid Maintains Bone Density in ART Users
People with HIV infection are at risk for thinner-than-normal bones and fractures. This risk for decreased bone density can arise because of multiple factors, some of which may be related to the impact of HIV on the immune system. Other factors are personal and may be related to at least the following issues:
- excessive alcohol intake
- tobacco smoking
- injecting street drugs
- use of corticosteroids
Studies have found that bone density tends to decrease by an average of 1% to 4% in the first year after ART is initiated. Bone density then tends to stabilize. The reason for this decrease in bone density is not clear.
Researchers in Atlanta, Georgia, conducted a small but well-designed clinical trial to assess the impact of a single infusion of the drug zoledronic acid (also known as zoledronate and sold under several brand names including Aclasta, Reclast and Zometa) on bone density in people initiating ART. The researchers found that a single infusion of zoledronic acid prevented ART-induced bone loss for one year (the duration of the study).
Researchers screened 343 potential volunteers before selecting 63 who were randomly assigned to receive one of the following interventions:
- ART + a single infusion of zoledronic acid -- 34 people
- ART + a single infusion of placebo (fake zoledronic acid) -- 29 people
The average profile of participants upon entering the study was as follows:
- age -- 39 years
- 79% men, 21% women
- most (80%) participants were black
- at least 70% of participants were smokers (a risk factor for osteoporosis)
Researchers did not recruit pregnant women or anyone with bone disease, vitamin D deficiency or stomach ulcers.
All participants received the following once-daily ART: atazanavir (Reyataz) + Truvada (tenofovir + FTC).
A Note on Assessment of Bone Health
Technicians analysed blood samples from participants for many proteins, but in particular for the following two proteins (or markers), which they used in part to assess bone health:
- CTx -- c-terminal telopeptide of collagen. Elevated levels of this substance suggest that bones are being torn down (the technical term for this is resorption)
- osteocalcin -- elevated levels of this protein suggest that bones are being built up
These blood tests are mainly used in research studies.
Technicians in the study also assessed bone health by having participants undergo low-dose X-ray scans called DEXA (dual-energy X-ray absorptiometry). Such scans are routinely used in clinics.
The study is expected to last 144 weeks and we now present preliminary findings.
Compared to placebo, levels of CTx fell significantly in zoledronic acid users by the following amounts at the following times:
- 73% decrease at week 12
- 65% decrease at week 24
Although the degree of decline in CTx was not as large at 48 weeks, it was still significantly greater than what was seen in people who received placebo.
Overall, this finding suggests that bone density was likely increasing in zoledronic acid users and decreasing in placebo users.
According to the results of DEXA scans of people who used zoledronic acid, bone mineral density rose by 8% in the spine at week 12, increased to 11% at week 24 and remained relatively stable by week 48. Similar trends were seen with DEXA scans of the hips.
In contrast, among placebo users bone mineral density fell by 2% at week 12, by 4% at week 24 and decreased slightly more at week 48.
Although the study was small, because of the relatively large effects captured by assessments, some sub-analyses were possible. Researchers found that zoledronic acid's beneficial effects were not affected by the following factors:
- age (comparing people under 40 with older people)
- viral load
- the presence of osteopenia at the start of the study
However, researchers did note that among placebo users men were more likely to have bone thinning than women. Among people who used zoledronic acid, men seemed to be less likely to lose bone to resorption.
No significant differences in side effects were reported between people who received zoledronic acid and those who received placebo. The researchers suggested that the drug was well tolerated.
Researchers elsewhere have tested zoledronic acid to stabilize bone density in HIV-positive people. You can find links to these other studies in the bone health resources section.
Ofotokun I, Titanji K, Vunnava A, et al. A single dose of zoledronic acid prevents antiretroviral-induced bone loss. Conference on Retroviruses and Opportunistic Infections, 22-25 February 2016, Boston, MA. Abstract 47.