Less fracture risk with denosumab than bisphosphonates in pre-treated osteoporosis

After 5 years of treatment, the relative risk (RR) for major osteoporotic fractures was significantly more reduced with denosumab as a second-line treatment in bisphosphonate-treated women with osteoporosis than by a change in bisphosphonate agent.

Guidelines recommend reassessment and suitable changes of medication in patients with osteoporosis who are not achieving an adequate bone mineral density response or are sustaining fractures on treatment [1,2]. The effectiveness of denosumab on fracture risk compared with bisphosphonate therapy in pre-treated women with osteoporosis was assessed by Prof. Jeffrey Curtis (University of Alabama at Birmingham, AL, USA) and colleagues [3]. Their retrospective study investigated post-menopausal women treated in US Medicare between 2012 and 2018.

All participants had prior bisphosphonates at baseline and were switched to second-line treatment with either denosumab or a different bisphosphonate agent. The participants were followed up for 5 years, their first fracture, or different drop-out reasons. Fracture risk was compared between the denosumab group (n=109,061) and either the alendronate (n=53,864), zoledronic acid (n=35,563), or an alternative oral bisphosphonate (n=101,684) group. The latter included people treated with alendronate, ibandronate, or risedronate.

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 major osteoporotic fractures at 5 years, denosumab led to greater reduced risks compared with the 3 other groups: RR 0.75 versus alendronate (95% CI 0.67–0.82), RR 0.69 versus any oral bisphosphonate (95% CI 0.61–0.76), and 0.69 versus zoledronic acid (95% CI 0.57–0.82). 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 3 groups, respectively. Furthermore, significant risk reductions for participants on denosumab were detected for non-vertebral, as well as hospitalised and non-hospitalised vertebral fractures. For all fracture types, the trajectory over time underlined an increasing risk reduction with a longer duration of medication.

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

1. Camacho PM, et al. Endocr Pract. 2020;26:S1-S46.
2. LeBoff MS, et al. Osteoporos Int. 2022;33:2049-2102.
3. Curtis JR, et al. Comparative effectiveness of denosumab versus bisphosphonates among treatment-experienced postmenopausal women with osteoporosis in the U.S. Medicare program. POS0089, EULAR 2024 Congress, 12–15 June, Vienna, Austria.

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Posted on 29 July 202429 July 2024