Zoledronic Acid Reduces Hip Fracture Risk in Postmenopausal Osteoporosis

Zoledronic acid is effective for reducing hip fracture risk among postmenopausal women with osteoporosis; however, its real-world effectiveness is diminished due to low adherence, as evidenced by study results published in Arthritis & Rheumatology.

The HORIZON Pivotal Fracture Trial (PFT; ClinicalTrials.gov Identifier: NCT00049829) established that zoledronic acid can effectively reduce the risk for hip fracture. In the current study, researchers sought to emulate the HORIZON-PFT trial using real-world data to evaluate how differences in treatment adherence impact the observed effectiveness of zoledronic acid in preventing hip fracture.

The study was designed as an active comparator, incident user cohort study (ClinicalTrials.gov Identifier: NCT04736693) using data from 2 United States claims databases. The researchers identified a cohort of women with osteoporosis aged 65 to 89 years who received their first annual infusion of zoledronic acid or initiated daily oral raloxifene from August 21, 2007, onward.

Eligibility criteria included a prior osteoporosis diagnosis or previous oral bisphosphonate prescription with a 2-year washout period. Within each database, zoledronic acid and oral raloxifene initiators were propensity score-matched in a 1:1 ratio for analysis.

The primary study outcome was hip fracture, with nonvertebral fractures assessed as a secondary outcome. Patients were followed for up to 18 months after cohort entry.

Overall, 52,631 eligible postmenopausal women with osteoporosis were identified, with 38,107 initiating zoledronic acid and 14,524 starting raloxifene. Women initiating zoledronic acid vs oral raloxifene were generally older, had more comorbidities, and used more healthcare services.

After matching, 12,651 women initiating zoledronic acid and 12,651 initiating oral raloxifene were included in the analysis.

After 18 months, the overall risk for hip fracture was 8.3/1000 events, which was similar to that found in the original HORIZON-PFT study (9.3/1000 events).

Fracture incidence rates were 5.8/1000 person-years vs 8.1/1000 person-years among zoledronic acid vs oral raloxifene initiators, respectively. This corresponded to a 28% risk reduction (hazard ratio [HR], 0.72; 95% CI, 0.51-0.92) among patients initiating zoledronic acid, or 2 fewer events per 1000 person-years of treatment (rate difference, -2.3; 95% CI, -4.10 to -0.56).   

Zoledronic acid showed a preventive effect on nonvertebral fracture risk, but the effect was attenuated when compared with the HORIZON-PFT trial results (HRs, 0.92 vs 0.75, respectively).

Additionally, results of sensitivity analyses found that the preventive effect of zoledronic acid on hip fracture increased between 12 and 18 months, with effects stabilizing after this time.

The researchers noted, “Limited adherence in clinical practice diminished the magnitude of [zoledronic acid’s] preventive effect and precluded long-term estimation of effectiveness in this setting.”

Study limitations include the lack of a true placebo comparator, potential under-diagnosis of osteoporosis and vertebral fractures in the real-world cohort, and the short follow-up duration.

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Rheumatology Advisor