FREEDOM

Denosumab for prevention of fractures in postmenopausal women with osteoporosis.

Cummings SR, San Martin J, McClung MR, et al. The New England journal of medicine 2009 · PMID 19671655 · doi:10.1056/nejmoa0809493

Question

Does six-monthly subcutaneous denosumab reduce vertebral, non-vertebral and hip fractures in postmenopausal osteoporosis?

Design

International multicentre double-blind placebo-controlled RCT over 3 years.

Patients

Postmenopausal women with a BMD T-score between -2.5 and -4.0 at the lumbar spine or total hip.

Intervention

Denosumab 60 mg subcutaneously every 6 months

Comparison

Placebo

Primary outcome

New vertebral fracture at 3 years

Key result

Denosumab significantly reduced new vertebral fractures (by about two thirds), with significant reductions in hip and non-vertebral fractures.

Limitations

Did not address what happens on stopping; later work showed rapid bone loss and rebound multiple vertebral fractures after discontinuation without follow-on therapy.

Impact on practice

Established denosumab as an option (NICE TA204) when bisphosphonates are unsuitable; UK guidance stresses it must not be stopped or delayed without transition to a bisphosphonate.