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Gnant et al. Denosumab reduces aromatase inhibitor-induced clinical fracture risk



DOI:10.1038/bonekey.2015.133

This large study conducted in 58 centers in Sweden and Austria investigated whether the increased risk of osteoporosis, fractures and osteopenia that accompanies treatment with aromatase inhibitors for early stage breast, could be counteracted by co-therapy with denosumab.

The participants received either denosumab 60 mg (n=1711) or placebo (n=1709), injected subcutaneously every 6 months. The trial is continuing; this paper is an analysis of data obtained once the first 247 clinical fractures were reported. The time from randomization to enter the study and the patient’s first clinical fracture was taken as the primary endpoint.

Denosumab-treated patients sustained their first clinical fracture after a significantly longer period, compared to participants in the placebo group (hazard ratio [HR] 0·50 [95% CI 0·39–0·65], P<0·0001). All subgroups of patients analyzed showed a significantly lower number of fractures after denosumab treatment (92 fractures) compared to controls (176 fractures). The number of adverse events, including those regarded as serious, did not differ significantly between the two groups (1366 [521 serious] for the denosumab group, 1334 [511 serious] for the placebo group). None of the participants were diagnosed with osteonecrosis of the jaw.

Editor’s comment: Denosumab, like zoledronate, is shown to be effective in reducing clinical fractures in hormone receptor-positive breast cancer patients receiving treatment with an aromatase inhibitor. It will be interesting to see if denosumab also improves disease-free survival of these patients, as was observed with zoledronate.


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