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Preventive effects of raloxifene treatment on agerelated weight loss in postmenopausal women.
Urano, T, Shiraki, M, Kuroda, T, Tanaka, S, Uenishi, K, Inoue, S
Journal of bone and mineral metabolism. 2017;(1):108-113
Abstract
Decline of body weight and body mass index (BMI) with aging is a major risk factor for osteoporosis and fracture, suggesting that treatment for osteoporosis may affect body composition. However, the effects of treatment for osteoporosis on body composition are not well known. The present study aimed to identify the relationship between raloxifene treatment and body composition markers. We measured bone mineral density (BMD), body composition, and bone remodeling markers in 236 Japanese postmenopausal women with raloxifene treatment (N = 50) and without treatment by any osteoporosis drug (N = 186) for 5 years and analyzed the relationship of these with BMD, BMI, body weight, and biochemical markers. The mean (SD) age of the participants was 65.5 (9.3) years. Percent-changes in body weight and BMI were significantly different between women taking raloxifene and those not taking any osteoporosis drugs (P = 0.03 and 0.048, respectively). Raloxifene treatment was a significant independent determinant of body weight and BMI. Long-term treatment with raloxifene prevents age-related weight loss.
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Overlapping and continued alendronate or raloxifene administration in patients on teriparatide: effects on areal and volumetric bone mineral density--the CONFORS Study.
Muschitz, C, Kocijan, R, Fahrleitner-Pammer, A, Pavo, I, Haschka, J, Schima, W, Kapiotis, S, Resch, H
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;(8):1777-85
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Abstract
Nine month teriparatide (TPTD) monotherapy followed by co-administration of raloxifene (RAL) or alendronate (ALN) for another nine 9 months resulted in incremental bone mineral density (BMD) increase. The aim of this study was to investigate the effects of continued antiresorptive treatments for 12 months in the extension phase. Postmenopausal women (n = 125) with severe osteoporosis on ongoing TPTD treatment for 9 months were randomized into three open-label groups for another 9 months: ALN (70 mg/week, n = 41), RAL (60 mg/d, n = 37) in addition to TPTD or no additional medication (n = 47) except Ca and vitamin D. After discontinuation of TPTD the respective antiresorptives were continued for a further 12 months, while patients in the TPTD monotherapy group received Ca and vitamin D. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), areal and volumetric BMD at the lumbar spine (LS) and hip were assessed. ALN resulted in continued BMD increase in LS (4.3 ± 1.5%; mean ± SD), femoral neck (4.2 ± 1.6%) and total hip (4 ± 1.6%; p < 0.001 for all), while RAL was only effective at the LS (2.4 ± 1.7%, p < 0.001) but no changes at the femoral neck (0.4 ± 1.4%) or total hip (-0.8 ± 1.5%) were observed. Cortical bone only increased in the ALN group (femoral neck 6.7 ± 2.7% and -1.3 ± 2.5%; total hip 13.8 ± 2.9% and -2.3 ± 2.5% for ALN and RAL, p < 0.001 for all; respectively). Analyzing the entire 30 months of therapy, the ALN group revealed the largest BMD increase in all regions. Our results suggest that the addition of ALN to ongoing TPTD and continuing ALN after TPTD was stopped may be beneficial for patients in terms of areal and volumetric BMD increase. Further research is warranted to determine the optimal timing of the initiation of the combination treatment, the respective antiresorptive medication and the potential benefit of this BMD increase regarding fracture prevention.
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A randomized phase II presurgical trial of weekly low-dose tamoxifen versus raloxifene versus placebo in premenopausal women with estrogen receptor-positive breast cancer.
Serrano, D, Lazzeroni, M, Gandini, S, Macis, D, Johansson, H, Gjerde, J, Lien, E, Feroce, I, Pruneri, G, Sandri, M, et al
Breast cancer research : BCR. 2013;(3):R47
Abstract
INTRODUCTION We previously demonstrated that 1 or 5 mg per day of tamoxifen (T) given for four weeks before surgery reduces Ki-67 in breast cancer (BC) patients to the same extent as the standard 20 mg/d. Given the long half-life of T, a weekly dose (10 mg per week (w)) may be worth testing. Also, raloxifene (R) has shown Ki-67 reduction in postmenopausal patients in a preoperative setting, but data in premenopausal women are limited. We conducted a randomized trial testing T 10 mg/w vs. R 60 mg/d vs. placebo in a presurgical model. METHODS Out of 204 screened subjects, 57 were not eligible, 22 refused to participate and 125 were included in the study. The participants were all premenopausal women with estrogen receptor-positive BC. They were randomly assigned to either T 10mg/w or R 60 mg/d or placebo for six weeks before surgery. The primary endpoint was tissue change of Ki-67. Secondary endpoints were modulation of estrogen and progesterone receptors and several other circulating biomarkers. RESULTS Ki-67 was not significantly modulated by either treatment. In contrast, both selective estrogen receptor modulators (SERMs) significantly modulated circulating IGF-I/IGFBP-3 ratio, cholesterol, fibrinogen and antithrombin III. Estradiol was increased with both SERMs. Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Moreover, a reduction of Ki-67 and a marked increase of sex hormone-binding globulin (SHBG) were observed in the active phenotype. CONCLUSIONS A weekly dose of tamoxifen and a standard dose of raloxifene did not inhibit tumor cell proliferation, measured as Ki-67 expression, in premenopausal BC patients. However, in the tamoxifen arm women with an extensive phenotype for CYP2D6 reached a significant Ki-67 modulation.
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Clinical significance of 1-year treatment with raloxifene on bone and lipid metabolism in Japanese postmenopausal women with osteoporosis.
Majima, T, Komatsu, Y, Shimatsu, A, Satoh, N, Fukao, A, Ninomiya, K, Matsumura, T, Nakao, K
Endocrine journal. 2007;(6):855-62
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It has been well established that raloxifene (RLX) has beneficial effects on bone primarily in Caucasian women. However, to date, there is a dearth of data for Japanese postmenopausal women. In this study, we prospectively evaluated the effects of RLX on bone and lipid metabolism in fifty Japanese postmenopausal patients with untreated osteoporosis. We measured bone mineral density (BMD) by dual-energy X-ray absorptiometry at 7 sites including the lumbar spine, femoral neck, and distal radius. BMD was significantly increased at the lumbar spine both at 6 months and at 12 months compared with at baseline (p<0.01 for both), although the possibility could not be completely excluded that this increase may be partly explained by an apparent increase induced by degenerative changes in lumbar vertebrae since we had no control subjects to compare and be more certain of the findings in this study. Both bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) significantly decreased both at 6 months (p<0.01 for both) and at 12 months (p<0.01 for both) compared with at baseline, but not below the lower limit of the reference value. Total cholesterol and low-density lipoprotein cholesterol were significantly improved while triglycerides and high-density lipoprotein cholesterol were unaltered. Although longer and larger studies with fracture endpoints are needed to draw definite conclusions, our findings suggest the favorable effects of RLX on bone and lipid metabolism in Japanese postmenopausal women with osteoporosis as in Caucasian women.
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Effectiveness and safety of raloxifene in post-menopausal females.
Abdullah, KN, Raoof, A, Raoof, M
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2005;(5):266-9
Abstract
OBJECTIVE To determine effects of raloxifene on lipid profile, breast tissue and endometrial thickness in post-menopausal women. DESIGN A longitudinal cohort study. PLACE AND DURATION OF STUDY The study was conducted at Department of Gynaecology and Obstetrics, PNS Shifa Hospital, Karachi over a period of one year. PATIENTS AND METHODS Fifty cases of postmenopausal women, aged 45-60 years, who had last menstrual period 2-8 years back, visiting Gynea OPD at PNS Shifa Hospital, Karachi, were included in the study. The subject received raloxifene (Evista) 60 mg once daily. The tests done at the start of study as baseline were serum lipid profile (HDL, LDL, total triglyceride and cholesterol levels), TVS (trans vaginal sonography) for endometrial thickness and mammography. The above tests were again done at the end of study after 12 months. The adverse effects were recorded. RESULTS Fifty women were enrolled for study out of which 48 completed the study that is 96%. Mean age was 54 years, SD = 3.95. The mean value of LDL, total triglyceride and cholesterol decreased by 15.2%, 1.2% and 10.2 % respectively. The change was statistically significant. (p < 0.001) HDL change was 0.665% and was not statistically significant. TVS, for endometrial thickness, and mammography for breast density showed no change. Adverse effects reported were hot flushes, leg cramps and vaginal symptoms in few cases. CONCLUSION Raloxifene therapy significantly decreases cardiovascular risk markers LDL, total triglyceride and cholesterol. No abnormal change in breast density and in endometrial thickness indicate good safety profile of this agent.
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Vitamin D insufficiency does not affect bone mineral density response to raloxifene.
Antoniucci, DM, Vittinghoff, E, Blackwell, T, Black, DM, Sellmeyer, DE
The Journal of clinical endocrinology and metabolism. 2005;(8):4566-72
Abstract
CONTEXT Vitamin D insufficiency and osteoporosis are common and often coexist in postmenopausal women. OBJECTIVE The objective of this study was to test whether the presence of vitamin D insufficiency at the initiation of raloxifene therapy affected the subsequent response of bone mineral density (BMD). DESIGN, SETTING, AND PARTICIPANTS We studied 7522 postmenopausal participants of the Multiple Outcomes of Raloxifene Evaluation, a placebo-controlled trial of the effects of raloxifene on BMD and fracture. INTERVENTION After enrollment, all participants began daily supplements of 500 mg calcium and 400-600 IU cholecalciferol; 1 month later, women were randomly assigned to placebo or raloxifene. MAIN OUTCOME MEASURE Serum levels of vitamin D [25-hydroxy vitamin D (25OHD)] were measured at enrollment, randomization, and 6 months later. We categorized participants' vitamin D status (deficient, insufficient, or sufficient) based on their randomization 25OHD level. We estimated the effects of treatment on BMD within these subgroups using linear regression models. RESULTS At enrollment, 3.2% of participants were vitamin D deficient, and 51.8% were insufficient; after 7 months of cholecalciferol supplementation, 0.2% of all participants remained D deficient, and 23.6% remained insufficient. The effects of raloxifene on hip and spine BMD did not vary by vitamin D status at randomization (P = 0.08 and P = 0.7, respectively). CONCLUSION We conclude that vitamin D status at initiation of raloxifene therapy does not affect the subsequent BMD response when coadministered with cholecalciferol and calcium. After 7 months of cholecalciferol therapy, very few women continued to have 25OHD levels in the deficient range; however, 25OHD levels remained suboptimal in nearly one fourth of the cohort. Additional research is needed to determine whether these observations can be generalized to other antiresorptive agents.
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[Effects of raloxifene on bone biomarkers in postmenopausal women on maintenance haemodialysis].
Matsuo, K, Fujinaga, M, Tsuchiya, K, Nakamoto, M, Yasunaga, C
Clinical calcium. 2005;:92-6; discussion 96-7
Abstract
Postmenopausal women on maintenance haemodialysis (MHD) has considerably higher risk of bone fracture than general population with combination of postmenopausal osteoporosis and renal osteodystrophy. However, the treatment of osteoporosis on MHD has not been established. Evidence indicates raloxifene (RLX), a selective estrogen receptor modulator, is effective for a protection of bone fracture without increasing of breast cancer and endometrial cancer. We hereby report short-term use experience of RLX for the postmenopausal MHD patients. Fifteen postmenopausal MHD patients with less than 80% of YAM bone density in DEXA administrated 60 mg RLX on every HD days (3 days/week). Serum NTX level significantly decreased after 6 months (180 +/- 18 vs. 95 +/- 12 nmol/BCE/L, p< 0.05), however, i-PTH did not have the significant difference. (115 +/- 23 vs. 157 +/- 29 pg/mL). RLX is effective for bone biomarker improvement in postmenopausal MHD patients. Further evaluation for the effectiveness and safety of RLX is necessary in the long term.
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Vascular events in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial: incidence, patient characteristics, and effect of raloxifene.
Duvernoy, CS, Kulkarni, PM, Dowsett, SA, Keech, CA
Menopause (New York, N.Y.). 2005;(4):444-52
Abstract
OBJECTIVE To determine the incidence of arterial and venous thromboembolic (VTE) events, to determine the effect of raloxifene on the incidence of combined vascular (arterial and VTE) events, and to identify patient characteristics associated with these vascular events, in women participating in the MORE trial. DESIGN In a post hoc analysis using MORE data, arterial, VTE, and combined vascular event rates were compared between participants receiving placebo (n = 2,576) and those receiving 60 mg/d of raloxifene (n = 2,557). Baseline characteristics were compared between those who did and did not experience an arterial event. The same analysis was performed for VTE events. RESULTS Overall, during a mean follow-up time of 41 months, 178 women experienced an arterial event and 40 experienced a VTE event. In the placebo group, the incidence of arterial events exceeded VTE events by at least sevenfold. Raloxifene had no significant effect on the incidence of combined vascular events in the overall cohort (hazard ratio 0.95, 95% CI, 0.73-1.24). In a subset of women retrospectively determined to be at increased cardiovascular risk, raloxifene was associated with a lower incidence of combined vascular events (hazard ratio 0.63, 95% CI, 0.40-0.97). Baseline characteristics differed between those who did and those who did not experience an arterial event, but this was generally not the case for VTE events. CONCLUSIONS Arterial events were more common than VTE events. The characteristics of women experiencing an arterial event differed from those experiencing a VTE event. Raloxifene had a neutral effect on the risk of combined vascular events in the overall population, and was associated with a reduced combined vascular event rate in women at increased cardiovascular risk. Additional studies are needed to confirm the effect of raloxifene on overall vascular outcomes.
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Effects of ospemifene and raloxifene on hormonal status, lipids, genital tract, and tolerability in postmenopausal women.
Komi, J, Lankinen, KS, Härkönen, P, DeGregorio, MW, Voipio, S, Kivinen, S, Tuimala, R, Vihtamäki, T, Vihko, K, Ylikorkala, O, et al
Menopause (New York, N.Y.). 2005;(2):202-9
Abstract
OBJECTIVE To compare ospemifene and raloxifene regarding their effects on hormones, lipids, genital tract, and tolerability in postmenopausal women. DESIGN A randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) of ospemifene or 60 mg (n = 29) of raloxifene for 3 months. RESULTS There were no significant differences in the baseline characteristics between study groups. In comparison with raloxifene, follicle-stimulating hormone levels decreased significantly more in the 90-mg ospemifene group and sex hormone-binding globulin levels increased more in all ospemifene groups. Total cholesterol and low-density lipoprotein cholesterol levels decreased more in raloxifene than in ospemifene groups, although the difference in low-density lipoprotein cholesterol between 90-mg ospemifene and raloxifene was not significant. Endometrial thickness did not change in any study group and endometrial biopsies showed atrophy in the majority of subjects at 3 months. All ospemifene groups demonstrated a clear estrogenic effect on the vaginal epithelium, as seen in Pap smears. This was in sharp contrast to the raloxifene group, which had no effect on the vaginal epithelium. Kupperman index decreased in all study groups during treatment. The adverse events were mild, mainly single cases, and no clustering of events was observed. There were no clinically significant abnormal findings in laboratory safety parameters. CONCLUSIONS Ospemifene, at the dose of 90 mg/day, was more estrogenic than raloxifene, as shown by changes in serum follicle-stimulating hormone and sex hormone-binding globulin levels. Neither agent stimulated endometrium, but in contrast to raloxifene, ospemifene had a clear estrogenic effect in the vagina. Further studies with ospemifene are needed in subjects with vaginal atrophy.
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Effect of raloxifene on serum triglycerides in women with a history of hypertriglyceridemia while on oral estrogen therapy.
Carr, MC, Knopp, RH, Brunzell, JD, Wheeler, BS, Zhu, X, Lakshmanan, M, Rosen, AS, Anderson, PW
Diabetes care. 2005;(7):1555-61
Abstract
OBJECTIVE Raloxifene hydrochloride is a selective estrogen receptor modulator that to date has not been shown to cause hypertriglyceridemia in normal, diabetic, or hypertriglyceridemic women. This study was designed to assess the effect of raloxifene on serum triglycerides in postmenopausal women who have a history of increased hypertriglyceridemia with oral estrogen therapy. RESEARCH DESIGN AND METHODS This was a single-center, uncontrolled, open-label study investigating the effects of 8 weeks of raloxifene (60 mg/day) therapy on plasma lipids. The study subjects were 12 postmenopausal women, ages 49-73 years, with a documented history of oral estrogen-induced hypertriglyceridemia (serum triglycerides > or =3.39 mmol/l [> or =300 mg/dl]). RESULTS At week 2 of the study, three (25%) of the subjects withdrew from the trial because they developed marked hypertriglyceridemia (>or =11.3 mmol/l [> or =1,000 mg/dl]) during raloxifene therapy. These three women had higher baseline triglyceride and glucose levels, were not being treated with lipid-lowering agents, and were more likely to have diabetes than the other study subjects. The remaining nine patients (75%) completed the 8-week trial and experienced a nonsignificant increase in mean triglyceride levels from baseline to end point. Raloxifene treatment also resulted in a significant 16% decrease in hepatic lipase activity and a 26% increase in HDL(2) levels (P = 0.013 and 0.03, respectively). CONCLUSIONS Patients with a previous history of hypertriglyceridemia on oral estrogen therapy should have serum triglyceride levels monitored closely after beginning raloxifene therapy and may even require fibrate therapy before beginning raloxifene.