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

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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.

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Conflict of interest

I.G. has received honoraria for lectures from Chugai Pharmaceutical Co., Ltd, Tokyo, Japan.

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Author notes

  1. Itsuo Gorai & Yaku Tanaka

    Present address: Department of Obstetrics and Gynecology, Hori Hospital, 292 Futatsubashi-cho, Seya-ku, Yokohama, Kanagawa, 246-0021, Japan

  2. Shin Hattori

    Present address: Department of Obstetrics and Gynecology, Odawara Municipal Hospital, Odawara, Kanagawa, 250-8558, Japan

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, International University of Health and Welfare Atami Hospital, Atami, Shizuoka, 413-0012, Japan

    Itsuo Gorai, Shin Hattori & Yaku Tanaka

  2. Department of Obstetrics and Gynecology, JA Yoshida General Hospital, Yoshida-cho, Hiroshima, 731-0595, Japan

    Yasuhisa Iwaoki

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  1. Itsuo Gorai
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  4. Yasuhisa Iwaoki
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Correspondence to Itsuo Gorai.

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Gorai, I., Hattori, S., Tanaka, Y. et al. Alfacalcidol-supplemented raloxifene therapy has greater bone-sparing effect than raloxifene-alone therapy in postmenopausal Japanese women with osteoporosis or osteopenia. J Bone Miner Metab 30, 349–358 (2012). https://doi.org/10.1007/s00774-011-0325-1

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  • DOI: https://doi.org/10.1007/s00774-011-0325-1

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