Alendronate and Risedronate: Efficiacy in Clinical Trials

To date, no clinical trial has directly compared the efficacy of alendronate and risedronate in osteoporosis treatment and prevention. Nevertheless, placebo-controlled studies of each agent individually indicate that both are effective and well tolerated in preventing postmenopausal osteoporosis (Table 1),(2-4) treating postmenopausal osteoporosis (Table 2),(5-7) and in glucocorticoid-induced osteoporosis (Table 3).(8-10)

Table 1:
Studies of Alendronate and Risedronate in Preventing Postmenopausal Osteoporosis

Studies with Risedronate

Investigators: Hooper et al(2)
Patients: 383 postmenopausal women 6 to 35 months after onset of menopause
Treatments: Placebo, risedronate 2.5 mg once daily, or risedronate 5.0 mg once daily for 2 years, in addition to 1 g once daily of calcium; prior or current estrogen use was not recorded
Results: Increased bone mineral density in the lumbar spine, femoral neck, and trochanter with 5.0 mg/day vs baseline (P <.05) and vs placebo (P < .05)
Adverse effects: Similar incidence of esophagitis and esophageal lesions in all three treatment groups

Investigators: Fogelman et al(3)
Patients: 543 postmenopausal women, onset of menopause within 2 years
Treatments: Placebo, risedronate 2.5 mg once daily, or risedronate 5.0 mg once daily for 2 years
Results: Increased bone mineral density in the lumbar spine, femoral neck, and trochanter with risedronate 5.0 mg/day vs baseline (P not reported) and vs placebo
(P <.001)
Adverse effects: Similar in the risedronate and placebo groups, even in patients with previous or active GI disease

Study with Alendronate

Investigators: McClung et al(4)
Patients: 447 postmenopausal women 6 to 36 months after onset of menopause who could have taken estrogen in the past year
Treatments: Placebo or alendronate 1 mg, 5 mg, 10 mg, or 20 mg once daily for 3 years
Results: Increased bone mineral density in the femoral neck and in the total hip with alendronate 5 mg/day vs baseline (P <.05); increased bone mineral density in the lumbar spine, femoral neck, and trochanter with alendronate 5 mg/day vs placebo (P < .001)
Adverse effects: Similar to placebo for all alendronate dosages

Table 2:
Studies of Alendronate and Risedronate in Treating Postmenopausal Osteoporosis

Studies with Risedronate

Investigators: Harris et al(5)
Patients: 2,458 postmenopausal women with one or more vertebral fractures and no estrogen use in the past month
Treatments: Placebo or risedronate 2.5 mg once daily or risedronate 5.0 mg once daily for 3 years
Results: Incidence of new vertebral fractures 11.3% with risedronate 5 mg/day vs 16.3% with placebo (P = .003); incidence of nonvertebral fractures 5.2% with risedronate 5 mg/day vs 8.4% with placebo (P = .02); increase in bone mineral density in the lumbar spine, femoral neck, and trochanter with risedronate 5 mg/day vs baseline (P <.05) and vs placebo (P < .05)
Adverse effects: Similar incidence of upper GI events in risedronate and placebo groups

Investigators: Reginster et al(6)
Patients: 1,226 postmenopausal women with two or more vertebral fractures and no estrogen use within the past 3 months
Treatments: Placebo, risedronate 2.5 mg once daily, or risedronate 5.0 mg once daily for 3 years
Results: Incidence of new vertebral fractures 18% with risedronate 5 mg/day vs 29% with placebo (P <.001); incidence of nonvertebral fractures 10.9% with risedronate 5 mg/day vs 16% with placebo (P = .06); bone mineral density in the lumbar spine, femoral neck, and trochanter increased with risedronate 5 mg/day vs baseline (P < .05) and vs placebo (P < .001)
Adverse effects: Similar incidence of adverse GI effects with risedronate vs placebo

Study with Alendronate

Investigators: Black et al(7)
Patients: 2,027 postmenopausal women with one or more vertebral fractures and no estrogen use within the past 6 months
Treatments: Alendronate 5 mg once daily (later increased to 10 mg once daily) or placebo for 3 years
Results: Incidence of vertebral fractures 8% with alendronate 10 mg/day vs 15% with placebo (P <.001); incidence of nonvertebral fractures 11.9% with alendronate 10 mg/day vs 14.7% with placebo (P = .063); increased bone mineral density in the lumbar spine, femoral neck, total hip, and trochanter in the alendronate 10 mg/day group vs placebo
(P <.001)
Adverse effects: No significant differences in upper GI events between treatment and placebo groups

Table 3:
Studies of Alendronate and Risedronate in Preventing and Treating Glucocorticoid-Induced Osteoporosis

Studies with Risedronate

Investigators: Cohen et al(8)
Patients: 224 men and women ages 18 to 65 who had begun long-term prednisone therapy (7.5 mg or more per day) within the past 3 months and had not used estrogen within the past year
Treatments: Risedronate 2.5 mg or 5.0 mg once daily or placebo for 1 year
Results: Significant change in bone mineral density of the lumbar spine in both risedronate groups vs baseline (P not recorded); increased bone mineral density in the lumbar spine, femoral neck, and trochanter with risedronate 5 mg/day vs placebo (P <.001)
Adverse effects: Similar incidence in all three groups

Investigators: Reid et al(9)
Patients: 290 men and women who had been on long-term prednisone therapy (7.5 mg or more per day) or equivalent for more than 6 months and had not used oral estrogen in the past 6 months
Treatments: Risedronate 2.5 mg or 5.0 mg once daily or placebo for 1 year Results: Increased bone mineral density in the lumbar spine, femoral neck, and trochanter with risedronate 5 mg/day vs baseline (P <.001) and vs placebo (P < .05); incidence of vertebral fractures 5% with risedronate 5 mg/day vs 15% with placebo (P = .042)
Adverse effects: Similar incidence of upper GI events in the risedronate 5 mg/day and placebo groups

Study with Alendronate

Investigators: Saag et al(10)
Patients: 477 men and women who had been taking prednisone (7.5 mg/day or more) or an equivalent for at least 4 months and could have used estrogen
Treatments: Alendronate 5 mg once daily or 10 mg once daily or placebo for 12 months
Results: Increased bone mineral density in the lumbar spine, femoral neck, trochanter, and total body with alendronate 10 mg/day vs baseline (P <.01) and vs placebo (P < .01)
Adverse effects: No difference in serious adverse events among the three groups; a small increase in nonserious upper GI effects occurred with alendronate 10 mg/day

Contraindications

Alendronate and risedronate are contraindicated in patients with:

—Hypocalcemia

—Known hypersensitivity to any component of the product

—Inability to stand or sit upright for at least 30 minutes

—Abnormalities of the esophagus that delay esophageal emptying, such as stricture or achalasia

—Renal impairment (creatinine clearance <30 mL/minute for risedronate or < 35 alendronate).

Cautions: Children, Pregnancy, Lactation

Alendronate and risedronate have not been tested in children younger than 18 years.

In pregnancy, both drugs are rated as risk category C-ie, adverse fetal effects have been shown in animals, but no human data are available. In animal studies, neonates born to mothers receiving alendronate or risedronate demonstrated decreased body weight and incomplete ossification of vertebral, sternal, and skull bones. Hypocalcemia and increased mortality in pregnant rats were also observed. Therefore, alendronate and risedronate should be used during pregnancy only if the potential benefit justifies the potential risks to the mother and fetus.

It is not known if alendronate and risedronate are excreted in human milk. Therefore, caution should be exercised when giving either drug to nursing women.