“Previous studies have shown that denosumab is more efficacious than alendronate in increasing bone mineral density (BMD), possibly the best proxy outcome for subsequent fracture risk. However, previous studies were underpowered to compare the risk of fracture in users of denosumab and alendronate. This is largest up-to-date study showing similar risks of hip and any fracture within 3 years in patients treated with denosumab and alendronate,” Dr. Alma Pedersen of Aarhus University Hospital in Denmark told Reuters Health by email.
Using national registries, the team investigated fracture risk in people aged 50 and older starting denosumab (4,624 patients) or alendronate (87,731 patients).
The three-year cumulative incidence of hip fracture was 3.7% in the denosumab cohort and 3.1% in the alendronate cohort, a difference that did not reach statistical significance. The three-year cumulative incidence of any fracture was 9.0% for both cohorts, the authors reported online April 19 in JAMA Network Open.
The adjusted hazard ratios for denosumab versus alendronate were 1.08 (95% confidence interval, 0.92 to 1.28) for hip fracture and 0.92 (95% CI, 0.83 to 1.02) for any fracture.
In separate analyses looking at patients with and without a history of fracture, no difference in hip fracture risk for denosumab versus alendronate was seen. However, in the analysis of risk for any fracture, denosumab was associated with a slightly reduced risk versus alendronate among patients with a history of fracture (aHR, 0.84, 95% CI, 0.71 to 0.98) and without such a history (aHR 0.77, 95% CI, 0.64 to 0.93).
The researchers note that denosumab has been shown to be more efficacious than alendronate in increasing BMD in postmenopausal women. However, a number of other factors, such as lifestyle, medication, comorbid conditions, or socioeconomic status, can influence the association of BMD with fracture risk “and could explain why higher efficacy of denosumab on BMD does not translate into higher effectiveness in reducing hip fracture risk.”
Summing up, Dr. Pedersen said, “Similar risk of hip and any fracture in denosumab and alendronate users was seen irrespective of sex, age and fracture history. Thus, higher effectiveness of treatment with denosumab in high risk patients could not be confirmed in our data.”
Support for the study was provided by Aarhus University Research Foundation and by the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation.