Risk of first hip fracture under treatment with zoledronic acid versus alendronate: a NOREPOS cohort study of 88,000 Norwegian men and women in outpatient care

Summary

We aimed to investigate the risk of hip fracture associated with zoledronic acid treatment compared to alendronate on a population level. The risk of hip fracture was lower in women using zoledronic acid and higher in women who had discontinued treatment. The findings support the effectiveness of intravenous bisphosphonate.

Purpose

To investigate whether zoledronic acid (ZOL) was associated with a lower risk of the first hip fracture than alendronate (ALN) in Norway using real-world data.

Methods

Nationwide data on drugs dispensed in outpatient pharmacies were individually linked with all hospital-treated hip fractures. Individuals aged 50–89 years without previous hip fracture were included at their first filling of a prescription for ALN or ZOL during 2005–2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for first hip fracture by time-varying exposure to ZOL versus ALN were estimated in sex-stratified flexible parametric survival analyses. Covariates included time-varying accumulated ALN exposure and comorbidity level expressed by the prescription-based Rx-Risk Comorbidity Index, marital status, education, and residential urbanity.

Results

Of 75,250 women who initiated treatment, 72,614 (96.5%) were exposed to ALN and 6366 (8.5%) to ZOL. Of 12,739 men who initiated treatment, 12,311 (96.6%) were exposed to ALN and 784 (6.2%) to ZOL. In women, the HR for first hip fracture was 0.75 (95% CI: 0.61–0.91) for ZOL versus ALN. In men, the corresponding HR was 0.59 (95% CI: 0.32–1.07). Discontinued treatment was associated with increased risk compared with current ALN treatment in women (HR: 1.33; 95% CI: 1.24–1.42, men: HR 1.13 (95% CI: 0.95–1.35)).

Conclusions

In women, the risk of first hip fracture when treated with ZOL was 25% lower than when treated with ALN. Discontinued treatment was associated with a 33% increase in hip fracture risk. Similar, albeit statistically non-significant, results were observed in men.