Effect of alendronate and vitamin D3 on fractional calcium absorption in a double-blind, randomized, placebo-controlled trial in postmenopausal osteoporotic women.

Menopause and increasing age are associated with a decrease in calcium absorption that can contribute to the pathogenesis of osteoporosis. We hypothesized that alendronate plus vitamin D(3) (ALN + D) would increase fractional calcium absorption (FCA). In this randomized, double-blind, placebo-controlled multicenter clinical trial, 56 postmenopausal women with 25-hydroxyvitamin D [25(OH)D] concentrations of 25 ng/mL or less and low bone mineral density (BMD) received 5 weekly doses of placebo or alendronate 70 mg plus vitamin D(3) 2800 IU (ALN + D). Calcium intake was stabilized to approximately 1200 mg/d prior to randomization. FCA was determined using a dual-tracer stable-calcium isotope method. FCA and 25(OH)D were similar between treatment groups at baseline (0.31 ± 0.12 ng/mL and 19.8 ± 4.7 ng/mL, respectively). After 1 month of treatment, subjects randomized to ALN + D experienced a significant least squares (LS) mean [95% confidence interval (CI)] increase in FCA [0.070 (0.042, 0.098)], whereas FCA did not change significantly in the placebo group [-0.016 (-0.044, 0.012)]. After ALN + D treatment, patients had higher 25(OH)D levels (LS mean difference 7.3 ng/mL, p < .001). The rise in serum 1,25-dihydroxyvitamin D(3) (p < .02) and parathyroid hormone (p < .001) were greater in the ALN + D group than in placebo-treated patients. ALN + D was associated with an increase in FCA of 0.07. To our knowledge, there is no other trial showing such a marked rise in calcium absorption owing to treatment with a bisphosphonate or owing to a small rise in 25(OH)D. This unique response of ALN + D is important for the treatment of osteoporosis, but the exact mechanism requires further study.

Changes in bone density and turnover after alendronate or estrogen withdrawal.

OBJECTIVE: To compare bone mineral density (BMD) and bone turnover changes after therapy withdrawal in postmenopausal women treated with alendronate or estrogen-progestin. DESIGN: In this randomized, blinded, multinational, placebo-controlled trial, 1,609 healthy postmenopausal women ages 45 to 59 years were assigned to receive alendronate, placebo, or open-label estrogen-progestin (conjugated equine estrogens plus medroxyprogesterone acetate or a cyclic regimen of 17 beta-estradiol, norethisterone acetate and estradiol). Of the original women, one third after year 2 and one third after year 4 were switched from alendronate to placebo, while remaining blinded to treatment assignment. The women taking estrogen-progestin in years 1 to 4 were followed off therapy in years 5 and 6. BMD at the lumbar spine and hip and biochemical markers of bone turnover were measured. RESULTS: The treatment groups described in the current report represent 860 women at baseline; 481 women entered year 5, and 430 completed 6 years. BMD steadily decreased in the placebo group during all 6 years. In contrast, spine and hip BMD increased during the first 4 years in the groups receiving daily continuous alendronate 5 mg and estrogen-progestin. During years 5 and 6, BMD decreased at the lumbar spine -2.42% (95% CI = -4.10, -0.74) and total hip -1.09% (-2.60, 0.41) in the group previously treated with alendronate 5 mg for 4 years. In comparison, large BMD decreases were observed at the spine [-7.69% (-8.96, -6.41)] and total hip [-5.16% (-6.30, -4.01)] among women who had received estrogen-progestin for 4 years. CONCLUSION: Alendronate produces greater residual skeletal effects than estrogen-progestin after therapy discontinuation.

Prevention of postmenopausal bone loss: six-year results from the Early Postmenopausal Intervention Cohort Study.

We report the effect of continuous treatment with alendronate for 6 yr vs. placebo in the Early Postmenopausal Intervention Cohort study. A total of 1609 healthy, early postmenopausal women were recruited; we describe results for the 585 women who received continuous placebo or alendronate (2.5 or 5 mg) daily for 6 yr. Bone mineral density (BMD) was evaluated at the lumbar spine, hip, forearm, and total body at baseline and annually thereafter. Bone turnover markers were measured every 6 months from baseline to yr 2 and annually thereafter. Adverse experiences, including upper gastrointestinal events and fractures, were recorded throughout the study. Women receiving placebo experienced progressive decreases in BMD at all skeletal sites. Patients receiving alendronate experienced significant gains in spine and hip BMD that were maintained through yr 6. Significantly greater, dose-related decreases in bone turnover markers in the alendronate groups vs. placebo occurred within the first year and were sustained through yr 6. Women receiving alendronate had adverse experience incidences similar to those receiving placebo. Fractures occurred in 11.5, 10.3, and 8.9% of women taking placebo, 2.5 mg alendronate, or 5 mg alendronate daily, respectively. Therapy with alendronate is an effective and promising strategy for the prevention of postmenopausal osteoporosis.