Just one dose of zoledronic acid given at the start of antiretroviral therapy (ART) may prevent ART-associated bone loss during the first 48 weeks of therapy, according to a study published online May 18 in Clinical Infectious Diseases.
The first 48 weeks of ART represent a critical time for bone loss and may provide a window of opportunity for prophylaxis. Zoledronic acid is a long-acting intravenous medication that slows bone resorption.
"[W]e demonstrated that ART-induced bone loss can be successfully prevented with an anti-resorptive," first author Ighovwerha Ofotokun, MD, from Emory University School of Medicine, Atlanta, Georgia, and colleagues write. "Specifically, the heightened bone resorption following ART initiation was completely blunted by [zoledronic acid,] resulting in durable [bone mineral density (BMD)] preservation at fracture-prone sites that lasted through 48 weeks."
Improved care for people with HIV/AIDS has lengthened the life spans of these patients, making the long-term complications of HIV infection an important issue. Both HIV infection and all types of ART have been linked to bone loss and increased fracture rates.
Past studies by these authors linked bone loss to the pronounced T-cell recovery that usually occurs at the initiation of ART. One study, performed in mice, suggested that zoledronic acid could prevent ART-associated bone loss.
For the current phase 2, double-blind placebo trial, the researchers recruited patients from the Grady Infectious Disease Program Clinic in Atlanta, Georgia, between January 2010 and January 2015. They enrolled 63 adult HIV-positive patients who did not have osteoporosis, were new to ART, and were starting on atazanavir/ritonavir+tenofovir/emtricitabine. Researchers randomly assigned participants to either a single dose of 5 mg zoledronic acid on the same day of ART initiation (n = 34) or placebo (n = 29). They assessed bone turnover markers and BMD at weeks 0, 12, 24, and 48.
Results showed that zoledronic acid had positive effects on bone resorption, which started as early as 12 weeks (73% reduction; P < .001) and continued through week 24 (65% reduction; P < .001) and up to week 48 (57% reduction; P < .001).
At 12 weeks, participants who received zoledronic acid had 8% higher BMD in the lumbar spine compared with placebo (P = .003). At weeks 24 and 48, BMD in the lumbar spine stayed at least 11% higher with zoledronic acid compared with placebo (P < .001 for both times). BMD in the hip and femoral neck showed similar trends.
No effect on virologic suppression and no reported serious adverse effects occurred with zoledronic acid.
Osteocalcin levels remained the same over the course of the study, indicating that zoledronic acid did not significantly affect bone formation (P = .22).
"This relative lack of effect on formation with a single dose of [zoledronic acid] is important, as remodeled bone that occurs with the prolonged use of bisphosphonates is paradoxically susceptible to micro-cracks," the authors write. "[Zoledronic acid] at a single dose was safe and well tolerated, and resulted in comparable rate of virologic suppression and similar magnitude of CD4 T-cell reconstitution."
As this was a small, single-center proof-of-concept trial that included mostly African-American men, the results may not generalize to more diverse populations. Also, the study could not look at long-term outcomes.
"These data define an optimal window for a pre-emptive intervention to forestall ART-induced bone loss and provide robust information needed to guide the design and implementation of larger confirmatory phase III, multicenter randomized clinical trials," the authors conclude.
The study was supported by the National Institute on Aging and the National Institute of Arthritis and Musculoskeletal Diseases The authors have disclosed no relevant financial relationships.
Single-Dose Drug Decreases Bone Loss in Newly Treated HIV. Medscape. May 23, 2016.