Treatment with denosumab reduces secondary fracture risk in women with postmenopausal osteoporosis

Abstract

Objectives A history of prior fracture is one of the strongest predictors of a future fragility fracture. In FREEDOM, denosumab significantly reduced the risk of new vertebral, non-vertebral, and hip fractures. We carried out a post-hoc analysis of FREEDOM to characterize the efficacy of denosumab in preventing secondary fragility fractures in subjects with a prior fracture.

Methods A total of 7808 women aged 60–90 years with a bone mineral density T-score of less than − 2.5 but not less than − 4.0 at either the lumbar spine or total hip were randomized to subcutaneous denosumab 60 mg or placebo every 6 months for 36 months. The anti-fracture efficacy of denosumab was analyzed by prior fracture status, to assess secondary fragility fracture, and by subject age, prior fracture site and history of prior osteoporosis medication use.

Results A prior fragility fracture was reported for 45% of the overall study population. Compared with placebo, denosumab significantly reduced the risk of a secondary fragility fracture by 39% (incidence, 17.3% vs. 10.5%; p < 0.0001). Similar results were observed regardless of age or prior fracture site. In the overall population, denosumab significantly reduced the risk of a fragility fracture by 40% (13.3% vs. 8.0%; p < 0.0001), with similar results observed regardless of history of prior osteoporotic medication use.

Conclusions Denosumab reduced the risk of fragility fractures to a similar degree in all risk subgroups examined, including those with prior fragility fractures. Identifying and treating high-risk individuals could help to close the current care gap in secondary fracture prevention.

Key words::

• POSTMENOPAUSAL OSTEOPOROSIS
• SECONDARY FRACTURE PREVENTION
• FRAGILITY FRACTURE
• DENOSUMAB
• FREEDOM STUDY

ACKNOWLEDGEMENTS

The authors thank Professor Steven Boonen (deceased) for his contribution to the acquisition, analysis and interpretation of the data. Medical writing support was provided by Kim Allcott (PhD) from Oxford PharmaGenesis Ltd (UK). Editing support was also provided by Claire Desborough of Amgen (Europe) GmbH.

Author contributions

S.P., R.R., H.R., J.D.A., J.C.G., R.G.F. and D.L.K. recruited subjects into the study, acquired and interpreted data, and reviewed draft versions of the manuscript. L.K.-K. and R.B.W. interpreted the data and helped to draft the manuscript. C.Z. interpreted the data and reviewed draft versions of the manuscript. A.W. analyzed and interpreted the data and reviewed draft versions of the manuscript. S.A. contributed to the study design, recruited subjects, acquired and interpreted data, and reviewed draft versions of the manuscript. All authors read and approved the final manuscript. No individuals received remuneration for authorship.

Conflict of interest S.P. has been a symposium speaker or advisory board member for Servier, Pfizer, GlaxoSmithKline, Abbott, Ferrer, Bioiberica, Shionogi and Amgen. He has also received research grants and/or consulting fees from Pfizer, Servier, Amgen, MSD, PregLem, Leon Farma, Gynea Laboratorios, Sandoz and Bayer. L.K.-K., C.Z., A.W. and R.B.W. are Amgen employees. R.R. has received consulting and lecturing fees from Amgen, GlaxoSmithKline, MSD, Danone and Servier. H.R. and J.C.G. have no competing interests. J.D.A. has acted as a consultant/speaker for Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott, and has conducted clinical trials for Amgen, Eli Lilly, Merck and Novartis. R.G.F. has received grants and/or research support from Amgen, Lilly and Biogen Idec, and has received honoraria for consultancy, speaker bureaus and/or advisory activities for Amgen, Forest, Lilly, Merck and Novartis. D.L.K. has received honoraria for advisory boards, speaker bureaus and contract research from Amgen, Pfizer, Merck, Eli Lilly, Novartis, Warner Chilcott and Johnson & Johnson. S.A. has received honoraria for an advisory board from Amgen.

Source of funding This manuscript was funded by Amgen (Europe) GmbH and GlaxoSmithKline; the FREEDOM study was funded by Amgen Inc.

Supplementary materials available online

Supplementary Table 1