SAN FRANCISCO, California — The RANK ligand (RANKL) inhibitor denosumab is more effective at increasing bone mass and decreasing important biochemical markers of bone turnover in postmenopausal women than alendronate (Fosamax^®), according to new research presented at the American College of Rheumatology Annual Scientific Meeting in San Francisco, California.¹

“The fact that bone density changes were greater than the most commonly used antiresorptive agent, alendronate, shows that denosumab is an effective agent," said lead researcher Chad Deal, MD, the head of the Center for Osteoporosis and Metabolic Bone Disease at the Cleveland Clinic in Ohio.

The new 1-year study comprised 1189 postmenopausal women with a mean lumbar spine T-score of -2.6. Patients were randomized to receive a 60 mg injection of denosumab every 6 months and a weekly oral placebo or an injection of placebo every 6 months plus 70 mgs of oral alendronate each week. All study participants took at least 500 mg of calcium and at least 400 mg of vitamin D daily.

Nearly twice as many women gained BMD with denosumab

More participants in the denosumab arm gained >3% BMD at the total hip at 1 year than did their counterparts who received alendronate, 62% versus 39%, respectively. Moreover, 77% of participants in the denosumab arm gained >3% BMD at the lumbar spine, compared with 66% of their counterparts in the alendronate group at the 1-year mark, the study showed.

Participants in the denosumab arm showed a rapid and sustained suppression of serum type 1 C-telopeptide from baseline levels. Procollagen type 1 N-propeptide levels decreased within 1 month of denosumab treatment and remained decreased through month 12. Adverse events were similar between both groups and no denosumab subjects developed anti-denosumab antibodies.

More good news on RANKL inhibitor presented at ACR

A related study found that denosumab significantly reduced hand cortical bone loss in rheumatoid arthritis (RA) patients receiving concomitant methotrexate over 12 months.²

In this Phase II study, patients who received a 60 mg dose of denosumab had significantly less decrease from baseline in the median cortical thickness ratio when compared with patients receiving placebo. At 1 year, patients who had received either 60 or 180 mg doses of denosumab had significantly less decrease from baseline in cortical thickness ratios than those study participants who received placebo. Moreover, erosion scores at 6 and 12 months also showed a decreased progression rate in the patients receiving denosumab as compared to placebo.

References

1. Deal C, Brown JP. Recker R, et al. Direct comparison of changes in bone density and bone turnover markers in postmenopausal women with low bone mass treated with 6-monthly denosumab or weekly alendronate (Fosamax). Presented at: American College of Rheumatology 2008 Annual Scientific Meeting; October 24-29, 2008; San Francisco, Calif. Presentation 2102
2. Sharp JT, Tsuji W, Harper-Barek C, et al. Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Presented at:  American College of Rheumatology 2008 Annual Scientific Meeting; October 24-29, 2008; San Francisco, Calif. Presentation 1001.