Issue: October 2009
October 01, 2009
2 min read

Denosumab: Fracture risk reduced in high-risk subset in FREEDOM

Issue: October 2009
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American Society for Bone and Mineral Research 31st Annual Meeting

Postmenopausal women with osteoporosis at high risk for fractures in the FREEDOM trial experienced consistent fracture risk reductions with denosumab, an investigational fully human monoclonal antibody, as compared with placebo, according to data presented here.

Prior presentation of FREEDOM results revealed significant fracture risk reductions, but the FREEDOM population of 7,808 women was at lower risk for fractures (45% considered high risk) than populations in comparable trials of zoledronic acid (HORIZON) and alendronate (Fosamax, Merck; FIT-I).

FREEDOM enrolled fewer patients with baseline femoral neck T-scores < –2.5 and vertebral fractures (eg, 2% vs. 63% for HORIZON and 100% for FIT-I), according to researcher Steven Boonen, MD, clinical director of the Leuven University Center for Metabolic Bone Diseases, Belgium.

Three-year fracture rates were 7.2% for new vertebral fractures, 8% for nonvertebral fractures and 1.2% for hip fractures.

Boonen presented post-hoc analysis data of a subset of women with more severe disease at baseline, two or more prevalent vertebral fractures and/or one or more prevalent vertebral fractures with moderate or severe deformity. The subset included those with baseline femoral neck T-scores ≤ –2.5 (36%). Researchers reported a 35% risk reduction with denosumab compared with placebo (17% vs. 49%; P=.0006) and a 55% risk reduction in new vertebral fractures in this high-risk group (31% vs. 71%; P=.0002).

Further post-hoc analysis examined hip fractures in women aged 75 years and older with baseline femoral neck T-scores ≤ –2.5 “to take into account the traumatic effect of age,” Boonen said. In this group, femoral neck fracture risk was reduced by 62% (22% vs. 82%; P=.0065).

“Risk reductions in vertebral, nonvertebral and hip fractures with denosumab in higher-risk subgroups were consistent with the treatment observed for the overall study population,” Boonen concluded.

The FDA is scheduled to make a decision about denosumab in October. If approved, denosumab would be marketed by Amgen under the brand name Prolia. – by Walter Alexander


In general, the worse the baseline bone density, the greater the fracture risk reduction so these results are not surprising. What is surprising is the large reduction in femoral neck fracture reduction - greater than would be expected with bisphosphonate use. I need to know data on how many patients had prior fractures, how many years patients had been on the drug and how many of this subset got serious complications, such as cellulitis.

Donald A. Bergman, MD

Endocrine Today Editorial Board member

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