The safety and effectiveness of risedronate sodium tablets 5 mg daily for the prevention of postmenopausal osteoporosis were demonstrated in a 2-year, double-blind, placebo-controlled study of 383 postmenopausal women (age range 42 to 63 years) within three years of menopause (risedronate sodium tablets 5 mg, N = 129). All patients in this study received supplemental calcium 1000 mg/day. Increases in BMD were observed as early as 3 months following initiation of risedronate sodium tablets treatment. Risedronate sodium tablets 5 mg daily produced significant mean increases in BMD at the lumbar spine, femoral neck, and trochanter compared to placebo at the end of the study (Figure 2). Risedronate sodium tablets 5 mg daily was also effective in patients with lower baseline lumbar spine BMD (more than 1 SD below the premenopausal mean) and in those with normal baseline lumbar spine BMD. Bone mineral density at the distal radius decreased in both risedronate sodium and placebo-treated women following 1 year of treatment.

The safety and effectiveness of risedronate sodium tablets 35 mg once-a-week for the prevention postmenopausal osteoporosis were demonstrated in a 1-year, double-blind, placebo-controlled study of 278 patients ( risedronate sodium tablets 35 mg, N = 136). All patients were supplemented with 1000 mg elemental calcium and 400 international units vitamin D per day. The primary efficacy measure was the percent change in lumbar spine BMD from baseline after 1 year of treatment using LOCF (last observation carried forward). Risedronate sodium tablets 35 mg once-a-week resulted in a statistically significant mean difference from placebo in lumbar spine BMD of +2.9% (least square mean for placebo -1.05%; risedronate +1.83%). Risedronate sodium tablets 35 mg once-a-week also showed a statistically significant mean difference from placebo in BMD at the total proximal femur of +1.5% (placebo -0.53%; risedronate +1.01%), femoral neck of +1.2% (placebo -1.00%; risedronate +0.22%), and trochanter of +1.8% (placebo -0.74%; risedronate +1.07%).

Combined Administration with Hormone Replacement Therapy   
The effects of combining risedronate sodium tablets 5 mg daily with conjugated estrogen 0.625 mg daily (N = 263) were compared to the effects of conjugated estrogen alone (N = 261) in a 1-year, randomized, double-blind study of women ages 37 to 82 years, who were on average 14 years postmenopausal. The BMD results for this study are presented in Table 5. 

Histology/Histomorphometry   
Bone biopsies from 53 postmenopausal women were obtained at endpoint. Patients had received risedronate sodium tablets 5 mg plus estrogen or estrogen-alone once daily for 1 year. Histologic evaluation (N = 47) demonstrated that the bone of patients treated with risedronate sodium tablets plus estrogen was of normal lamellar structure and normal mineralization. The histomorphometric parameter mineralizing surface, a measure of bone turnover, was assessed based upon baseline and post-treatment biopsy samples from 12 patients treated with risedronate sodium tablets plus estrogen and 12 treated with estrogen-alone. Mineralizing surface decreased in both treatment groups (median percent change: risedronate sodium tablets plus estrogen, -79%; estrogen-alone, -50%), consistent with the known effects of these agents on bone turnover.