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

Abstract

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 þ 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 þ 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 AE 0.12 ng/ mL and 19.8 AE 4.7 ng/mL, respectively). After 1 month of treatment, subjects randomized to ALN þ 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 [À0.016 (À0.044, 0.012)]. After ALN þ 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 þ D group than in placebo-treated patients. ALN þ 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 þ D is important for the treatment of osteoporosis, but the exact mechanism requires further study. ß

Increased Calcium Absorption From Synthetic Stable Amorphous Calcium Carbonate: Double-Blind Randomized Crossover Clinical Trial in Postmenopausal Women

“…We also found a significant negative correlation between the baseline FCA from CCC and the relative ratio of FCA, indicating that when absorption is relatively low, the beneficial effect on calcium absorption of a product with a better bioavailability will be greater. This finding is in agreement with a previous report that showed a greater treatment‐related increase in FCA among subgroups of women with lowest baseline FCA after treatment with alendronate combined with vitamin D 3 . Thus, our results suggest that subjects with relatively low calcium absorption would benefit more from ACC treatment than those with intact calcium gastrointestinal absorption (ie, obese women).…”

Vitamin D supplementation and calcium absorption during caloric restriction: a randomized double-blind trial

“…It is possible that the shorter half-life of vitamin D 2 compared with vitamin D 3 may have contributed to negative findings in some of these studies. In contrast, only 70 mg vitamin D 3 /wk (w10 mg/d) plus alendronate in postmenopausal women increased fractional calcium absorption by 0.07, but the large rise was attributed to the alendronate effect on serum PTH and 1,25(OH) 2 D 3 (34). In adolescent girls and young children with rickets, supplementation with vitamin D 3 showed no increase in calcium absorption (15,35).…”

Hormonal and dietary influences on true fractional calcium absorption in women: role of obesity

“…However, serum 25OHD is an indirect marker of 1,25(OH) 2 D 3 that affects Ca absorption, so it is not surprising that it does not always show a positive relationship with TFCA in adults [6, 14, 15, 42] and in children [20, 42, 43]. In contrast, supplementation with a large dose of vitamin D increases short-term Ca absorption [19], but this is not always shown with lower doses [21, 44]. Serum calcitriol shows a linear relationship with Ca absorption in both children and adults [6, 14, 15] and is an independent predictor of calcium absorption in women [6, 14, 42], consistent with our findings in the current dataset over a wider age and BMI range than in previous studies.…”