Alendronate treatment is well-tolerated and improved bone mineral density (BMD), with no safety concerns in children and adolescents with perinatally acquired HIV, according to a study recently published in Clinical Infectious Diseases.
Compared with children and adolescents without HIV, those who are perinatally infected have lower BMD; this may be related to antiretroviral therapy (ART). However, low BMD is also associated with several other factors, including body composition abnormalities, concomitant medications (corticosteroids, medroxyprogesterone), delayed puberty, and vitamin D insufficiency. Bisphosphonates, such as alendronate, reduce the process of bone resorption via the inhibition of osteoclasts; compared with in adults, this effect may be more pronounced in children and adolescents as a result of more rapid bone turnover in the children.
Although previous studies have shown that bisphosphate therapy reduces the rate of fractures in adults with osteoporosis and prevents/reduces BMD loss in adults with HIV receiving ART, there has been no formal study investigating this therapy among youths with HIV. Therefore, this study evaluated the safety of the oral bisphosphonate alendronate and its effect on BMD among youth with HIV and low BMD (ClinicalTrials.gov identifier: NCT000921557).
Researchers conducted a double-blind, cross-over study designed to assess the efficacy and safety of once-weekly alendronate at 48 and 96 weeks of treatment in Brazil and the United States. In total, 50 children and adolescents receiving ART for perinatally acquired HIV, aged 11 years to <25 years, who had a low lumbar spine BMD (Z-score, <−1.5) were included in the study cohort. These patients received either alendronate (n=32) or placebo (n=18) once weekly, and all patients received daily calcium carbonate and vitamin D supplementation. Patients were also asked to engage in regular weight-bearing exercise. The results for the initial 48 weeks of the trial are summarized here.
The results suggest that 48 weeks of alendronate significantly improved lumbar spine and whole-body BMD with no safety concerns. Five (16%) patients receiving alendronate and 2 (11%) patients receiving placebo developed grade ³3 abnormal laboratory values, signs, or symptoms. Compared with placebo, mean increases in lumbar spine BMD were significantly larger in the alendronate group (7% vs 20%; P <.001). Similar results and improvements were also observed for whole-body BMD. Results also showed that among younger participants, alendronate had larger predicted mean improvements in lumbar spine BMD among younger participants compared with patients who received placebo, as well as older participants. Among participants aged 11 years to <15 years at entry, predicted mean increases in lumbar spine BMD over the course of 1 year for participants who received alendronate compared with placebo in participants were 27% (95% CI, 16%-37%) compared with 6% (95% CI, −7% to 20%) in those aged ≥19 years.
After 48 weeks of treatment, there were no reported cases of jaw osteonecrosis, nonhealing fractures, or atrial fibrillation, leading the investigators to conclude that alendronate treatment was well-tolerated.
Overall, the study authors concluded that, “While impact on fractures and peak bone mass is unknown, alendronate treatment decreases fracture risk in children with other chronic diseases affecting bone, and similar long-term outcomes are anticipated in HIV-infected children and adolescents.”
Reference Jacobson DL, Lindsey JC, Gordon C, et al. Alendronate improves bone mineral density in perinatally HIV-infected children and adolescents with low bone mineral density for age. Clin Infec Dis. doi:10.1093/cid/ciz957/5579856