Alfacalcidol-supplemented raloxifene therapy has greater bone-sparing effect than raloxifene-alone therapy in postmenopausal Japanese women with osteoporosis or osteopenia

Abstract

Vitamin D insufficiency is prevalent in osteopenic and osteoporotic postmenopausal women. The persistent increase in circulating parathyroid hormone (PTH) caused by vitamin D insufficiency reduces bone density response to antiresorptive agents in these postmenopausal women. It is not well known whether administration of raloxifene might increase serum PTH secondary to the suppression of serum calcium in postmenopausal women with osteopenia or osteoporosis. We tried to assess whether raloxifene might affect serum PTH and whether the addition of alfacalcidol to raloxifene therapy could have favorable effects on bone mineral density (BMD) and bone turnover as compared to raloxifene-alone therapy in postmenopausal Japanese women with osteoporosis or osteopenia (≤2.0 SD based on young Japanese women). A total of 169 subjects were randomly assigned to groups receiving 60 mg raloxifene (R), or 1 μg alfacalcidol (D), or a combination of both (R + D) for 2 years. Serum levels of 25-hydroxyvitamin D [25(OH)D] were measured at randomization. The modified 'intention to treat' method was used. We compared the groups using a Tukey-Kramer test for changes in L- and TH-BMD and calcium metabolism when significant differences were found using one-way ANOVA. The parameters in each group during the experimental period were analyzed by means of paired t tests. Baseline 25(OH)D and i-PTH were 23.7 ng/ml and 38.4 pg/ml, respectively. At 6 months, i-PTH demonstrated a significant increase (+21.0%) in the R-group whereas significant decreases in i-PTH were observed in the D-group and combination-group (-15.9 and -8.9%, respectively). There were significant increases in L-BMD in the R + D-group (+4.1% at 1 year and +4.7% at 2 years, P < 0.0001) and in the R-group (+2.9% at 1 year and +2.8% at 2 years, P < 0.001), but the difference between the groups did not reach a significant level. Vitamin D status at randomization did not affect the subsequent BMD response in coadministration of alfacalcidol with raloxifene. Supplementation with alfacalcidol to raloxifene therapy demonstrates a greater bone-sparing effect by suppressing the secondary increment of serum PTH than when raloxifene is used alone.

Quality of life in Japanese women with postmenopausal osteoporosis treated with raloxifene and vitamin D: post hoc analysis of a postmarketing study

“…Vitamin D, supplemented to a higher than physiological concentration, significantly alleviates secondary hyperparathyroidism when serum 25(OH)D 3 concentration is lower than 50 nmol/L (20 ng/mL) 54 . Cotreatment of active vitamin D 3 with antiresorptives, such as alendronate, risedronate, and raloxifene, has been shown to be superior in increasing BMD and reducing the incidence of fractures in patients with osteoporosis 29,30 .…”

“…This is particularly important because vitamin D insufficiency and secondary hyperparathyroidism, which decreases the beneficial effect of antiresorptives on BMD 30,51 , are common in the elderly population and often associate with osteoporosis 53 . Vitamin D, supplemented to a higher than physiological concentration, significantly alleviates secondary hyperparathyroidism when serum 25(OH)D 3 concentration is lower than 50 nmol/L (20 ng/mL) 54 .…”

“…Vitamin D is essential for the optimal action of antiresorptive therapies to increase BMD, thereby reducing clinical fractures and pain 29,30,51,52 . This is particularly important because vitamin D insufficiency and secondary hyperparathyroidism, which decreases the beneficial effect of antiresorptives on BMD 30,51 , are common in the elderly population and often associate with osteoporosis 53 .…”

“…Vitamin D and calcium are essential to obtain the optimal benefit of antiresorptive therapies in patients with osteoporosis 29,30 . However, intake of vitamin D is inadequate in a large proportion of the Japanese population 31 .…”

Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia)

“…Evidence of safety was reported in 1229–33,35–38,40–42 of the 15 publications. The method of randomization and allocation (eg, randomly generated treatment codes, random self-drawing of prepared sealed envelopes) was described in four29,32,33,35 of the seven randomized controlled trials. Only the double-blind placebo-controlled trial35 and an open-label randomized controlled trial30 described whether randomization and allocation were blinded.…”