Greater Fracture Risk Reduction With Denosumab Than Bisphosphonates in Osteoporosis

Jul 10, 2024

Denosumab significantly reduced the relative risk (RR) of fractures more than bisphosphonates in pretreated women with osteoporosis.

Denosumab significantly reduced the relative risk (RR) of fractures more than bisphosphonates in pretreated women with osteoporosis. Depending on the different comparative agents, denosumab led to an RR of 0.60–0.75 for all major osteoporotic fractures after five years.

How does the effectiveness of denosumab on fracture risk compare with bisphosphonate therapy in pre-treated women with osteoporosis? Jeffrey Curtis, MD, and colleagues assessed this question in a retrospective study on post-menopausal women treated in US Medicare between 2012 and 2018.¹

All included patients had prior bisphosphonates at baseline and were switched to second-line treatment with either denosumab or a different bisphosphonate agent. Participants were followed up for five years, their first fracture, or different drop-out reasons. The results were evaluated by comparing risks between the denosumab group (n=109,061) and either the alendronate (n=53,864), zoledronic acid (n=35,563), or an oral bisphosphonate group. The latter subsumed alendronate, ibandronate, or risedronate (n=101,684).

Baseline characteristics included a mean age of 76.1 to 77.3 years, a history of any osteoporotic fracture in 19.0–26.7%, and a Charlson Comorbidity Index of ≥3 in 26.2–32.0%. The researchers pointed out that participants on denosumab were, on average, older, had more comorbidities, were at a greater risk for fracture, and used more medications than those in the other groups.

Regarding all major osteoporotic fractures at five years, denosumab led to greater reduced risks compared with the three other groups: RR 0.75 (95% CI, 0.67–0.82) versus alendronate, RR 0.69 (95% CI, 0.61–0.76) versus oral bisphosphonate, and 0.69 (95% CI, 0.57–0.82) versus zoledronic acid.

Similarly, denosumab reduced the risk of hip fractures by 37% (RR, 0.63; 95% CI, 0.51–0.75), 45% (RR, 0.55; 95% CI, 0.42–0.68), and 38% (0.62; 95% CI, 0.32–0.91) in comparison to the other three groups, respectively. Furthermore, significant risk reductions for participants on denosumab were detected for nonvertebral fractures and hospitalized and non-hospitalized vertebral fractures.

Dr. Curtis and colleagues expressed their hope that this large comparative study may help guide physicians, patients, and policymakers on optimal treatment strategies for second-line management of osteoporosis.