Neue Studien

Denosumab bei postmenopausaler Osteoporose

Denosumab for prevention of fractures in postmenopausal women with osteoporosis.
Cummings SR et al. New England Journal of Medicine 2009; 361 (10.1056/NEJMoa0809493) published August 11, 2009 at NEJM.org.

Objective
To assess whether Denosumab, a fully monoclonal antibody to the receptor activator of nuclear factor–kappa B ligand (RANKL) is able to prevent fractures in postmenopausal women with osteoporosis.

Patients and Methods
A total of 7868 women aged 60-90 yrs with a bone mineral density (BMD) T-score of less than -2.5, but nor less than -4.0 at the lumbar spine (LS) or the total hip (TH) were recruited. All subjects were randomly assigned to receive either 60mg denosumab (DEN) or placebo (PBO) subcutaneously every 6 months for 36 months. The primary outcome was new vertebral fracture, whereas secondary endpoints included nonvertebral and hip fractures.

Results
As compared to PBO, DEN significantly reduced the risk of new radiographic vertebral fracture with a cumulative incidence of 2.3% for DEN vs. 7.2% for PBO group and a relative risk reduction of 68%. The risk of hip fracture was also significantly reduced by DEN vs PBO (relative decrease of 40%). The risk of nonvertebral fracture was in addition also significantly reduced by DEN vs. PBO (relative decrease of 20%). There was no serious adverse event (AE) and both DEN and PBO group were similar in terms of tolerability and safety.

Conclusion
The subcutaneous administration of denosumab, the first fully human monoclonal antibody to RANKL, given at 60mg twice yearly for a total of 36 months, was associated with a significant reduction of the risk of both vertebral, hip and nonvertebral fractures in women with postmenopausal osteoporosis. The substance was in addition well tolerated and did not present with any serious safety issue.

Comment
The discovery of the RANK Ligand pathway a couple of years ago represents a very significant advance in the understanding of bone biology. The publication of the results of the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every six Months) study in the August 11,2009 issue of the NEJM, is a nice demonstration that targeting the RANK Ligand pathway with denosumab could represent a promising new approach to treat bone loss in postmenopausal women with osteoporosis.

Daniel Uebelhart, MD / 18.08.09

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