Annals of Long Term Care

San Francisco, CA, October 24-29, 2008

Denosumab Associated With Significant Increases in Bone Mineral Density in Patients With Osteoporosis Previously Treated With Alendronate

Poster

San Francisco— In patients with osteoporosis previously treated with alendronate, switching to denosumab is associated with a significant increase in bone mineral density (BMD) as well as a rapid and significant reduction in serum CTX, report investigators at the American College of Rheumatology/Association of Rhematology Health Professionals (ACR/ARHP) Annual Scientific Meeting.

Because of the chronic nature of osteoporosis and the frequent need for long-term treatment to reduce fracture risk and maintain BMD, a better understanding of the safety and efficacy of switching patients from standard bisphosphonate therapies to newer therapies is needed. Denosumab, a fully monoclonal antibody directed against an essential mediator of osteoclast formation, function, and survival (the RANK ligand), has been shown to increase BMD in postmenopausal women with low bone mass as well as treatment-naïve patients.

To evaluate the safety and efficacy of transitioning patients with osteoporosis from a bisphosphonate such as alendronate to denosumab, Jacques P. Brown, MD, CHUQ, Laval University, Quebec City, Canada, and colleagues conducted an international multicenter, double-blind study in which postmenopausal women with low BMD previously treated with alendronate were randomized to continued treatment with alendronate (n = 251) or denosumab (n = 253). Eligibility criteria included prior treatment with branded or generic alendronate (70 mg once weekly) or equivalent for at least 6 months prior to screening and a BMD measurement corresponding to a T-score of ≤ -2.0 and ≥ -4.0 at the lumbar spine or proximal femur (ie, total hip).

Patients excluded from the study included those with any disease or condition known to affect bone metabolism, prior use of IV bisphosphonate, and vitamin D level of < 20 ng/mL. Patients who met study criteria and participated in the study had a mean age of 67.7 years, a mean lumbar spine BMD T-score of -2.63, and received prior bisphosphonate therapy for a median of 36 months.

Prior to randomization, all patients received open-label alendronate (70 mg once weekly) during a 1-month run-in phase. Patients were then randomized to continued branded alendronate or denosumab (60 mg every 6 mo). All patients also received daily calcium and vitamin D supplements.

At 12 months, the study found a significantly greater increase in total hip BMD from baseline in patients who switched to denosumab compared to those who continued on alendronate (1.90% vs 1.05%; P < 0.0001).

Patients treated with denosumab also showed significant gains in BMD at the lumbar spine, femoral neck, and trochanter as compared to those treated with alendronate (P < 0.03), and these gains were noted as early as 6 months from treatment initiation. At 12 months, all skeletal sites showed a significant gain in BMD in the denosumab-treated patients (P < 0.01).

The study also found that denosumab significantly reduced serum CTX levels, a biochemical marker of bone turnover in serum, as compared to alendronate beginning 5 days after treatment and at all points throughout the study (P < 0.0001). In the patients who continued on alendronate, serum CTX levels remained near baseline levels.

The study found no differences in adverse events between the two treatment groups, with 197 adverse events (15 serious events) reported with denosumab and 196 adverse events (16 serious events) reported with alendronate. No patient reported hypocalcemia.