Short-term alendronate prevents ART-associated bone loss in PWH

The short-term use of alendronate prior to antiretroviral therapy (ART) initiation in people with HIV (PWH) helps prevent ART-associated bone mineral density (BMD) loss, according to the APART* study presented at CROI 2021.

This phase IV, multicentre, prospective, double-blind, placebo-controlled trial involved 50 PWH (median age 35 years, 86.0 percent male, median BMI 24.0 kg/m²) who were randomized to receive either oral alendronate 70 mg weekly (n=24) or placebo (n=26), commencing within 2 weeks before ART** initiation, in addition to calcium/vitamin D3 supplementation, for up to 14 weeks. [CROI 2021, abstract 96]

A significantly higher total hip BMD was observed among patients treated with alendronate compared with placebo at 14 weeks (+1.88 percent vs -0.65 percent; median difference, 2.04 percent; p=0.03) and 50 weeks (+0.5 percent vs -2.7 percent; median difference, 3.1 percent; p=0.02).

Similarly, those who received alendronate had a significantly higher lumbar spine BMD at 14 weeks (+1.24 percent vs -0.96 percent; median difference, 2.4 percent; p=0.01) and 26 weeks (+0.05 percent vs -2.5 percent; median difference, 3.1 percent; p=0.03) than those on placebo.

However, by week 50, there was a decline in lumbar spine BMD in the alendronate arm, though to a lesser extent than that seen in the placebo arm (-1.4 percent vs -3.7 percent; median difference, 2.3 percent; p=0.10), with the between-group difference not statistically significant.

“[Of note,] our findings of preserved BMD did not persist to week 50 at the lumbar spine,” said study author Dr Tara McGinty from the Centre for Experimental Pathogen Host Research at University College Dublin in Dublin, Ireland.

Both the alendronate and the placebo arms showed no significant differences in any treatment-emergent (TE) and treatment-related (TR) adverse events (AEs; 78.2 percent vs 69.3 percent [TEAEs] and 52.5 percent vs 38.5 percent [TRAEs]). Gastrointestinal disorders and musculoskeletal and connective tissue disorders were the most commonly reported AEs.

“It is well established that PWH have a high prevalence of low BMD and increased fracture incidence compared to the general population. It is also accepted that HIV is an independent risk factor for low BMD,” said McGinty.

“However, an interesting phenomenon [that is] not fully understood is the consistent loss of BMD that occurs during the first year or post-ART initiation,” she noted.

“In conclusion, short course generic oral alendronate at ART initiation prevented ART-associated bone loss over 48 weeks at the total hip … A protective effect was also observed at the lumbar spine but this [was] limited to the first 24 weeks,” said McGinty. Despite the small sample size with limited female presentation, “a clear signal of benefit was still apparent,” she noted.

“An inexpensive, easily accessible, safe, and well-tolerated drug, generic alendronate is a potential option for preventing bone loss associated with ART initiation – this may be of particular relevance in resource-limited settings,” she added.

*APART: Alendronate for Prevention of ART-associated bone loss

**Tenofovir disoproxil fumarate/emtricitabine and a third agent