Alendronate and Risedronate for the Treatment of Postmenopausal Osteoporosis: Clinical Profiles of the Once-Weekly and Once-Daily Dosing Formulations

Ronald Emkey, MD

Disclosures

Medscape General Medicine. 2004;6(3):6 

In This Article

Clinical Efficacy of the Bisphosphonates: Once-Weekly Administration

A randomized, placebo-controlled trial comparing once-daily, twice-weekly, and once-weekly alendronate was conducted on 1258 women aged 42 to 95 years with postmenopausal osteoporosis over a period of 2 years.[40,41] Patients enrolled in the study had prior vertebral or hip fracture, or BMD of the lumbar spine or femoral neck of at least -2.5 SD below the normal reference mean. Patients were randomized to receive alendronate 70 mg once weekly, 35 mg twice weekly, or 10 mg/day. Patients also received calcium 500 mg/day and vitamin D 250 IU/day. Results of this study showed similar reductions in bone turnover marker assays and increases in BMD among the 3 groups ( Table 3 ). After 2 years of therapy, patients in the weekly and twice-weekly alendronate (70 mg and 35 mg, respectively) groups had a mean increase in lumbar spine BMD of 6.8% and 7.0%, respectively; patients in the daily alendronate (10 mg) group experienced a 7.4% increase. Differences in BMD at the lumbar spine and hip were not statistically significant among the 3 groups. Effects of alendronate on bone turnover markers were seen as early as 1 month after initiation of therapy regardless of the dosing regimen. All the treatment regimens resulted in a reduction of bone turnover marker levels to the premenopausal reference range.[42] Clinical fractures captured as adverse events were similar among the 3 groups. Reductions in bone turnover and increases in lumbar spine BMD continued to be similar among the once-daily, twice-weekly, and once-weekly regimens over a second year.[41] Incidence rates of clinical fractures also continued to be similar during the 1-year extension.

In a multicenter, randomized, double-blind study, the efficacy and safety of risedronate administered once weekly (35 mg/week or 50 mg/week) was compared with the 5-mg once-daily risedronate regimen in 1456 postmenopausal women with osteoporosis (lumbar spine BMD T-score of < -2.5 or of < -2 with at least 1 prevalent fracture).[43,44] After 1 year of treatment, risedronate 35 and 50 mg once weekly were shown to be comparable to risedronate 5 mg once daily in increasing BMD and decreasing markers of bone turnover ( Table 4 ).[43] BMD of the lumbar spine (the primary efficacy end point), femoral neck, and trochanter increased significantly from baseline in all 3 treatment groups, with no statistically significant differences between the once-weekly risedronate (35 mg or 50 mg) regimens and the once-daily (5 mg) regimen at 12 months. Similarly, markers of bone turnover, including serum bone-specific alkaline phosphatase and urinary N-terminal telopeptides of type I collagen, decreased significantly from baseline in all 3 treatment groups as early as 3 months, with no statistically significant differences between the once-weekly risedronate (35 mg or 50 mg) regimens and the once-daily (5 mg) regimen at 12 months.

In a retrospective comparison by Watts and colleagues,[44] fracture risk reduction with risedronate 35 mg once weekly was evaluated using historical risedronate 5 mg/day and placebo-controlled groups constructed by matching patients from the VERT-MN and -NA studies to patients in the once-weekly trial using the once-weekly trial's enrollment criteria.[44] No statistically significant differences in vertebral fracture incidence were observed between the 5-mg/day groups from the phase 3 (1.7%; VERT-MN and -NA) and once-weekly (1.5%) studies. Relative reduction in the risk of new vertebral fractures with risedronate once weekly (77%) was similar to the 1-year reductions (65% and 61%) reported for once-daily risedronate.[33,34] Fracture risk reduction with risedronate 35 mg once weekly continued to be significant over 2 years compared with placebo.[45]

An open-label study evaluated changes in BMD and tolerability to risedronate 30 mg once weekly over a period of 2 years.[46,47] Mean increases in BMD were significantly higher in year 2 than in year 1 (P < .001 for trend at all 3 sites) vs baseline.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....