MONTREAL, Quebec—The anti-RANKL drug denosumab reduced spinal fracture in postmenopausal women with osteoporosis by 68% versus placebo, Steven Cummings, MD, of the University of California San Francisco, reported at the 2008 American Society of Bone and Mineral Research meeting.1 Related studies showed that denosumab was more effective than alendronate at improving bone mineral density (BMD) and reducing bone turnover markers in women previously treated with alendronate.2 In addition, patients generally preferred a 6-monthly sc shot of denosumab to a weekly oral dose of alendronate.3  The studies were sponsored by Amgen Inc.

Dr. Cummings reported results of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months) phase III trial, which enrolled 7868 women aged 60 to 90 years who had osteoporosis, defined as lumbar spine or total hip T-score <-2.5 and ≥-4.0. Mean lumbar spine T-score was -2.8. At entry, 23% of subjects had prevalent vertebral fractures.

Subjects were randomized to 3 years of 60 mg of denosumab sc every 6 months or to a matching placebo. All subjects also received 1000 mg of elemental calcium and up to 800 IUs of vitamin D per day.

After 3 years of treatment, Dr. Cummings found that
  • new vertebral fractures in 2.3% of denosumab patients vs 7.2% of placebo patients, a 68% reduction (P = .0001)
  • new nonvertebral fractures in 8.5% of denosumab patients vs 8% with placebo, a 20% reduction (P = .011).
  • new hip fractures in 0.7% of denosumab patients vs 1.2% of placebo patients, a 40% reduction (P = .036).
  • 9% greater lumbar spine BMD with denosumab and 6% greater total hip BMD (both P = .0001).

The study did not compare denosumab to current therapies, but the fracture-reduction results are comparable to those of once-yearly zoledronic acid (Reclast®, Novartis Pharmaceuticals Corp) infusions.

In related work, data from a randomized, double-blind, double-dummy, active-controlled trial that directly compared the effects of denosumab to alendronate in 1189 subjects showed that denosumab decreased bone turnover markers significantly more than alendronate and produced greater BMD increases at the total hip. Among those who reported a preference, 77% preferred the injection to the tablet (P <.0001).2

“Denosumab suppressed bone remodeling and increased BMD at all measured sites more than [alendronate]. BMD gains were consistent across different levels of baseline bone turnover. The differences in results between these drugs may be due to their different mechanism of inhibiting bone turnover,” wrote lead investigator Jacques P. Brown, MD, of CHUQ Laval University in Quebec City, Canada.

The twice-yearly denosumab injections, described as “kind of like a flu shot for osteoporosis” by Amgen research chief Roger S. Perlmutter, MD, PhD, was well-received by patients.

References

1. Cummings SR, McClung MR, Christiansen C, et al. A phase III study of the effects of denosumab on vertebral, nonvertebral, and hip fracture in women with osteoporosis: Results from the FREEDOM trial. Presented at: ASBMR 2008 meeting; September 15, 2008; Montreal, Canada. Presentation 1286.
2. Brown JP, Deal C, de Gregorio LH, et al. Effect of denosumab vs alendronate on bone turnover markers and bone mineral density changes at 12 months based on baseline bone turnover level. Presented at: ASBMR 2008 meeting; September 15, 2008; Montreal, Canada Presentation 1285.
3. Gold DT, Horne R, Borenstein J, et al. Preference and satisfaction with a 6-monthly subcutaneous injection versus a weekly tablet for treatment of low bone mass. Presented at: ASBMR 2008 meeting; September 15, 2008; Montreal, Canada. Presentation M372.