Early Postmenopausal Bone Loss is Prevented by Estrogen and Partially by 1α-OH-vitamin D3: Therapeutic Effects of Estrogen and/or 1α-OH-vitamin D3

Abstract

A total of 79 Japanese women who were within 5 years of menopause were randomly assigned 1alpha-hydroxyvitamin D3 [1alpha(OH)D3] 1.0 microg/day, conjugated estrogens 0.625 mg/day, a combination of both, or control (no treatment). Lumbar spine and proximal femur bone mineral density (BMD) and biochemical indices were monitored over 2 years. In the 1alpha(OH)D3-treated group, there was a nonsignificant decrease in lumbar spine BMD compared with controls, and no significant loss in the femoral neck compared with controls. In the estrogen-treated group, there was a nonsignificant increase in spine BMD (+2.17% in the first year and +1.71% in the second year), and no loss in femoral neck BMD. The combination of conjugated estrogens +1alpha(OH)D3 was more effective in increasing BMD in the spine (+3. 68% in the first year and +3.63% in the second year) and femur (+2. 56% in the first year and +4.44% in the second year) BMD. There was a significant difference in lumbar spine BMD in both the first and second years between the combination-treated group and the 1alpha(OH)D3-treated and control groups (P < 0.01). Serum osteocalcin (OC) significantly decreased in the combination-treated group (-23.8% in the first year) and the estrogen-treated group (-37. 6% and -41.2% at 6 and 18 months, respectively), and serum alkaline phosphatase (Alp) decreased significantly in the first year in the combination-treated (-31.5%), estrogen-treated (-27.3%), and 1alpha(OH)D3-treated (-7.9%) groups, whereas serum OC increased (+45. 4% in the first year) in women without treatment. The results of this study indicate that early postmenopausal bone loss in the femoral neck is prevented by conjugated estrogens, 1alpha(OH)D3, or both, whereas bone loss in the spine is not prevented by 1alpha(OH)D3. Estrogen proves effective in preventing early postmenopausal bone loss by markedly inhibiting bone turnover. Moreover, a synergistic bone-sparing effect can be expected when estrogen is administered concomitantly with 1alpha(OH)D3 rather than when used alone.

Dose effects of oral estradiol on bone mineral density in Japanese women with osteoporosis

“…Similar results were reported from a study in Japanese women within 5 years after menopause 26 . Thus, the change in BMD demonstrated in this study is of similar magnitude to existing published data, although the studies are not directly comparable.…”

Efficacy of Combined Treatment with Raloxifene and Alfacalcidol on Bone Density and Biochemical Markers of Bone Turnover in Postmenopausal Osteoporosis

“…Some investigators have already examined the combination therapy of estrogens for HRT and ALF. Gorai et al [26] found a synergistic effect of HRT and ALF on early postmenopausal bone loss to be only marginal. In addition, neither Gallagher et al [27] nor Komulainen et al [28] could find any further beneficial effects on bone loss in the combination therapy of HRT and ALF compared with those in HRT alone.…”

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

“…We have already reported that a synergistic bone-sparing effect can be expected when estrogen is administered concomitantly with alfacalcidol [1a-hydroxyvitamin D 3 ] rather than when used alone in postmenopausal Japanese women with osteopenia, suggesting that vitamin D status is not sufficient in early postmenopausal Japanese women [16]. However, in the previous study, serum levels of 25(OH)D were not measured when the subjects were enrolled in the clinical trial [17].…”