A pharmacological review of raloxifene

Bryant, Henry U.; Glasebrook, Andrew L.; Yang, Na; Sato, Masahiko

doi:10.1007/bf01771666

Cited by 67 publications

(45 citation statements)

References 55 publications

(59 reference statements)

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“…Results from the current study are consistent with previous reports demonstrating a bone protective effect with Ral in Ovx rats [4][5][6][7]19]. Ral has been shown to fully protect Ovx-…”

Section: Discussionsupporting

confidence: 95%

Raloxifene and teriparatide (hPTH 1-34) have complementary effects on the osteopenic skeleton of ovariectomized rats

Bryant

Zeng

et al. 2005

J Bone Miner Metab

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The skeletal efficacy of raloxifene (Ral) plus weekly teriparatide [recombinant human parathyroid hormone (1-34), TPTD] combinations relative to each treatment alone or sequentially were evaluated in osteopenic, ovariectomized rats. In the first study, 6-month-old Sprague-Dawley rats were ovariectomized (Ovx) and permitted to lose bone for 1 month before treatment for the following 3 months. Raloxifene (Ral, 1 mg/kg/day orally) was evaluated alone and in combination with TPTD (10 or 30 microg/kg/week) administered weekly by subcutaneous injection. QCT, biomechanical testing, and histomorphometry were used to quantitate skeletal effects. Weekly TPTD alone at either dose had no skeletal effect relative to Ovx. Daily Ral prevented further loss of vertebral bone mineral density (BMD), resulting in BMD that was significantly greater than Ovx, but significantly less than age-matched, sham-Ovx, vehicle controls (sham). The raloxifene plus 30 microg/kg/week TPTD group had vertebral BMD that was significantly greater than Ovx, Ral alone, and both TPTD dose-alone groups. Therefore, the Ral plus TPTD group completely restored bone mass to sham levels. Compression testing of lumbar vertebra L5 confirmed increased strength for both Ral plus TPTD combinations relative to Ovx, with strength not different from sham. Histomorphometry of the proximal tibial metaphysis showed that Ovx significantly increased eroded surface and bone formation compared to sham. Raloxifene treatment restored eroded surface and bone formation rate back to sham levels. Raloxifene plus TPTD at 30 microg/kg/week resulted in a significantly higher mineral appositional rate compared to Ral and sham, which was not different from Ovx and TPTD alone. Raloxifene plus TPTD at both doses had eroded surfaces that were significantly less than Ovx but not different from sham or Ral alone. In a sequential study, 6-month-old Ovx rats were permitted to develop osteopenia for 2 months before a daily TPTD 80 microg/kg/day subcutaneous injection was initiated. Following 2 months of TPTD treatment, animals were either (1) continued on TPTD, (2) discontinued from TPTD, (3) switched to Ral 3 mg/kg/day, oral, or 17 alpha-ethynyl estradiol (EE2) 0.1 mg/kg/day, oral, for another 2 months. Raloxifene and EE2 maintained most of TPTD-induced new bone in Ovx rats by preventing the increase in bone turnover rate after withdrawal of TPTD. Raloxifene also restored the elevated bone formation activity induced by TPTD to the level of sham. These data suggest that Ral and TPTD have complementary interactions in osteopenic, Ovx rats. Raloxifene inhibited bone resorption, and reduced high bone turnover without significantly retarding TPTD stimulation of bone formation activity.

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“…Results from the current study are consistent with previous reports demonstrating a bone protective effect with Ral in Ovx rats [4][5][6][7]19]. Ral has been shown to fully protect Ovx-…”

Section: Discussionsupporting

confidence: 95%

Raloxifene and teriparatide (hPTH 1-34) have complementary effects on the osteopenic skeleton of ovariectomized rats

Bryant

Zeng

et al. 2005

J Bone Miner Metab

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“…However, the importance of non-classical signalling for the bone protective effects of raloxifene in vivo needs to be further analysed. Raloxifene antagonizes oestrogen-induced stimulation of uterine weight gain via pharmacological competition for the ERs (Bryant et al 1996). Furthermore, raloxifene has been proposed to have antagonistic effects in uterus in shamoperated mice (Erlandsson et al 2002); however, we did not detect any antagonistic effect on classical signalling by raloxifene in uterus.…”

Section: Discussioncontrasting

confidence: 84%

In vivo activation of gene transcription via oestrogen response elements by a raloxifene analogue

Engdahl

Jochéms

Gustafsson

et al. 2009

Journal of Endocrinology

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Raloxifene is a selective oestrogen receptor modulator with tissue-specific effects. The mechanisms behind the effects of raloxifene are partly unclear, and the aim of the present study was to investigate whether raloxifene can activate the classical oestrogen-signalling pathway in vivo in three known oestrogen-responsive organs, uterus (reproductive organ), bone (non-reproductive organ) and thymus (immune organ). For this purpose, we have used reporter mice with a luciferase gene under control of oestrogen-responsive elements (EREs), enabling detection of in vivo activation of gene transcription via the classical oestrogen pathway. Three-month-old ovariectomized ERE-luciferase mice were treated with the raloxifene analogue (LY117018), oestradiol (OE 2 ) or vehicle for 3 weeks. Luciferase activation was measured in bone, uterus and thymus, and compared to bone parameters, and uterus and thymus weights. The raloxifene analogue affected bone mineral density (BMD) to the same extent as OE 2 , and both treatments resulted in increased luciferase activity in bone. As expected, OE 2 treatment resulted in increased uterus weight and increased uterine luciferase activity, while the effect of LY117018 on uterus weight and luciferase activity was modest and significantly lower than the effect of OE 2 . LY117018 and OE 2 treatment resulted in similar luciferase activation in thymus. However, only OE 2 treatment resulted in thymic atrophy, while no effect on thymus weight was seen after LY117018 treatment. In summary, the raloxifene analogue LY117018 can activate the classical oestrogen pathway in bone, uterus and thymus in vivo, and this activation is associated with BMD and uterus weight, but not thymus weight.

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“…Raloxifene is rapidly absorbed after oral administration [17,18]. Absolute raloxifene bioavailability is 2%; approximately 60% of an oral dose is future science group future science group www.futuremedicine.com absorbed and enterohepatic cycling occurs.…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 99%

“…Chemistry Raloxifene hydrochloride is a SERM that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism and blood clotting [17][18][19][20]. It is a ben-…”

Section: Introduction To Raloxifenementioning

confidence: 99%

Raloxifene: A Selective Estrogen Receptor Modulator for Reducing the Risk of Invasive Breast Cancer in Postmenopausal Women

Vogel

2007

Womens Health (Lond Engl)

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Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism and blood clotting. Tamoxifen is the prototypical selective estrogen receptor modulator and reduces the risk of both in situ and invasive breast cancers by half when compared with placebo. The limitations on the use of tamoxifen for breast cancer risk reduction relate to its well-known, but rare, side effects. A number of clinical trials have established the benefit of raloxifene on osteoporosis and fracture. Raloxifene significantly improves serum lipids and serum markers of cardiovascular disease risk, but has no significant effect on the risk of primary coronary events. In several osteoporosis trials and the Raloxifene Use for The Heart (RUTH) trial, raloxifene decreased the risk of estrogen receptor-positive breast cancer by 44-90%. In the Study of Tamoxifen And Raloxifene (STAR) trial, the effect of raloxifene on invasive breast cancer was equivalent to that of tamoxifen, with more favorable effects on uterine malignancy and clotting events. Symptomatic side effects are acceptable. In total, the available data indicate that raloxifene represents an acceptable alternative to tamoxifen for the reduction of the risk of postmenopausal breast cancer in high-risk women. The potential market for a compound shown to reduce the risk of breast cancer in postmenopausal women who are at increased risk for breast cancer is more than 10 million women in the USA alone.

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A pharmacological review of raloxifene

Cited by 67 publications

References 55 publications

Raloxifene and teriparatide (hPTH 1-34) have complementary effects on the osteopenic skeleton of ovariectomized rats

Raloxifene and teriparatide (hPTH 1-34) have complementary effects on the osteopenic skeleton of ovariectomized rats

In vivo activation of gene transcription via oestrogen response elements by a raloxifene analogue

Raloxifene: A Selective Estrogen Receptor Modulator for Reducing the Risk of Invasive Breast Cancer in Postmenopausal Women

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