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

Tolerability

Data from the 2 FIT trials showed a similar incidence of upper gastrointestinal adverse events in the alendronate group when compared with the placebo group. The incidences for upper gastrointestinal events vs placebo were 41.3% and 40.0%, respectively, in the trial evaluating women with existing vertebral fractures[25] and 47.5% and 47.2%, respectively, in the trial in women with low bone density but no fractures.[26] Incidences of upper gastrointestinal adverse events were similar with alendronate 10 mg/day and 70 mg once weekly (23.5% and 22.4%, respectively) at 1 year,[40] and at 2 years (30.0% and 29.3%, respectively).[41]

In clinical trials of postmenopausal women with osteoporosis, the incidence of adverse events was similar with risedronate taken for up to 5 years as compared with placebo.[33,34,35,38,43] The risedronate clinical trials program did not exclude patients with a history of or active gastrointestinal disease or taking medications for active upper gastrointestinal disorders (eg, histamine H2-receptor antagonists, proton pump inhibitors, or antacids). In a pooled analysis of 9 clinical trials of risedronate administered once daily, out of 10,068 patients, 1197 used histamine H2-receptor antagonists or proton pump inhibitors, 6145 had a history of upper gastrointestinal disease, and 3900 had active upper gastrointestinal disease.[48] In each of the above-mentioned subgroups, the incidence of upper gastrointestinal adverse events was similar between patients randomized to risedronate and those randomized to placebo. Among 349 patients who underwent endoscopy, which was recommended for patients with moderate to severe upper gastrointestinal symptoms, endoscopic findings were similar across the risedronate and control groups. Risedronate administered once daily has a gastrointestinal safety profile similar to placebo in patients at risk for upper gastrointestinal disorder.

In the comparison between risedronate 5 mg once daily and risedronate 35 mg or 50 mg once weekly, the percentage of women who reported adverse events, and specifically upper gastrointestinal adverse events, was similar among all 3 treatment groups; 17.5%, 18.4%, and 18.7% for risedronate 5 mg/day, 35 mg once weekly, and 50 mg once weekly, respectively.[43] Thus, risedronate once daily and risedronate once weekly are equally well-tolerated in women with postmenopausal osteoporosis.

Following approval when alendronate was first used in the clinical practice setting, patients reported upper gastrointestinal distress more frequently than expected.[49,50,51,52,53,54] Adverse events included acute esophagitis with exudative inflammation, ulcerations, upper gastrointestinal bleeding, and esophageal stricture requiring dilation. The relatively high incidence of postmarketing reports may have been related to poor patient instruction and an underappreciation by physicians of proper bisphosphonate dosing techniques. A recent review of upper gastrointestinal event data indicates that clinical reports of esophagitis appear to have declined and suggests that the decline may be due to proper bisphosphonate administration.[28]

Proper bisphosphonate administration may have contributed in part to the lower frequency of adverse event reporting following the launch of risedronate. However, in a 2-week head-to-head trial in postmenopausal women (N = 515), the overall incidence of asymptomatic gastric ulcers diagnosed by endoscopy was significantly lower in women receiving risedronate 5 mg/day vs alendronate 10 mg/day (P < .001).[55] Gastric esophagogastroduodenoscopy (EGD) scores were also significantly lower in patients receiving risedronate (P < .001).

In contrast to the 2-week head-to-head trial, in a 4-week trial comparing the tolerability of alendronate, risedronate, and aspirin, risedronate 30 mg/day and alendronate 40 mg/day were found to have similar tolerability profiles.[56] The incidence of gastric ulcers and/or erosions was approximately 3% for both alendronate and risedronate, all of which were asymptomatic. However, dosages of both agents were much higher than the recommended daily dosage for the treatment of osteoporosis.

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