Raloxifene

Raloxifene (RAL) and alendronate (ALN) improve the biomechanical properties of bone by different mechanisms. The goal here was to investigate the effects of combination treatment of RAL and ALN on the biomechanical properties of vertebral bone. Six-month-old Sprague-Dawley rats (n = 80) were randomized into five experimental groups (sham, OVX, OVX + RAL, OVX + ALN, and OVX + RAL + ALN; n = 16/group). Following euthanization, structural and derived material biomechanical properties of vertebral bodies were assessed. Density and dynamic histomorphometric measurements were made on cancellous bone. The results demonstrate that the structural biomechanical properties of vertebral bone are improved with the combination treatment. Stiffness and ultimate load of the OVX + RAL and OVX + ALN groups were significantly lower than those of sham animals, but the combination treatment with RAL + ALN was not significantly different from sham. Furthermore, the OVX + RAL + ALN group was the only agent-treated group in which the ultimate load was significantly higher than that in OVX animals (p < .05). Cancellous bone fractional volume (BV/TVcanc) and bone mineral density (aBMD) also were improved with the combination treatment. BV/TVcanc of the OVX + RAL + ALN group was 6.7% and 8.7% greater than that of the OVX + RAL (p < .05) and OVX + ALN (p < .05) groups, respectively. Areal BMD of the OVX + RAL or OVX + ALN groups was not significantly different from that in OVX animals, but the value in animals undergoing combination treatment was significantly higher than that in OVX or OVX + RAL animals alone and not significantly different from that in sham-operated animals. Turnover rates of both the RAL + ALN and ALN alone groups were lower than in the RAL-treated alone group (p < .05). We conclude that the combination treatment of raloxifene and alendronate has beneficial effects on bone volume, resulting in improvement in the structural properties of vertebral bone. © 2011 American Society for Bone and Mineral Research.

Three impurities were detected during the impurity profile study of raloxifene hydrochloride by reverse phase gradient high performance liquid chromatographic method (HPLC) whose area percentage ranged from 0.06 to 0.15%. The product ion spectrum of these impurities and Raloxifene was recorded in LCMS and the fragmentation patterns of these impurities were observed and these three impurities displayed identical molecular ion at m/z 488. A thorough study was undertaken to characterize these impurities. They were isolated from enriched mother liquors by preparative HPLC. Based on the spectral data (1H,13C NMR, 1D NOE, 2D NMR and Mass), the structure of these impurities 1-3 were characterized as 1-(2-(4-(6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophene-3-carbonyl)phenoxy)ethyl)-1-methylpiperidin-1-ium (Impurity-1), [6-Hydroxy-2-(4-methoxy phenyl)-benzo[b]thiophen-3-yl]-[4-(2-piperidin-1-yl-ethoxy) phenyl]-methanone (Impurity-2) and [2-(4-hydroxy-phenyl)-6-methoxy-benzo[b]thiophen-3-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone (Impurity-3).

We explored psychometric properties of the Osteoporosis Assessment Questionnaire 2.0 in terms of reliability, validity, and responsiveness with generic, clinical, demographic, and preference-based data collected from a population of postmenopausal women with osteoporosis. The Multiple Outcomes of Raloxifene Evaluation study was a randomized, placebo-controlled, multinational clinical trial evaluating efficacy and safety of raloxifene. The Osteoporosis Assessment Questionnaire 2.0, a generic quality of life measure (Nottingham Health Profile), and a preference-based measure (Health Utilities Index) were administered at baseline and annually. Psychometric properties of the 14 Osteoporosis Assessment Questionnaire 2.0 domains were evaluated by standard statistical techniques. This study included a subset of 1477 women from the Multiple Outcomes of Raloxifene Evaluation study population completing the questionnaires. Mean (standard deviation) age was 68.4 (6.8) years. Prevalent vertebra...

This review will focus on antioestrogens and selective oestrogen receptor modulators (SERMS). The more traditional SERMS, clomiphene citrate and tamoxifen, will be reviewed along with such modern drugs as raloxifene and faslodex, with emphasis upon their actions on breast, uterus, bone and lipids. The future potential of these medications, in the management of oestrogen-dependent gynaecological conditions such as endometriosis, dysfunctional uterine bleeding, fibroids and breast cancer will be discussed.

BACKGROUND Patients routinely cite the media, after physicians and pharmacists, as a key source of information on new drugs, but there has been little research on the quality of drug information presented. We assessed newspaper descriptions of drug benefits and harms, the nature of the effects described and the presence or absence of other important information that can add context and balance to a report about a new drug. METHODS We looked at newspaper coverage in the year 2000 of 5 prescription drugs launched in Canada between 1996 and 2001 that received a high degree of media attention: atorvastatin, celecoxib, donepezil, oseltamivir and raloxifene. We searched 24 of Canada&#39;s largest daily newspapers for articles reporting at least one benefit or harm of any of these 5 drugs. We recorded the benefits and harms reported and analyzed how such information was presented; we also determined whether clinical or surrogate outcomes were mentioned; if and how drug effects were quantif...

Introduction The purpose of this study was to compare the effects of different postmenopausal hormone therapy regimens, namely conjugated equine estrogens (CEE), CEE plus medroxyprogesterone acetate (MPA), tibolone, and raloxifene on cerebral blood flow and cognitive functions. Methods A total of 64 healthy postmenopausal women admitted to the Department of Obstetrics and Gynecology, Cumhuriyet University, Turkey were included in this study. Patients were divided into five groups with respect to the treatment protocols: CEE 0.625 mg/day (n=13); CEE 0.625 mg/day + MPA 2.5 mg/day (n=14); tibolone 2.5 mg/day (n=11); raloxifene 60 mg/day (n=9); and control (n=17). The CEE group included only women with surgical menopause. Those who were on hormonal therapy, who had previously used hormonal therapy, who had neurological disorders, or who did not accept the longterm follow-up were excluded from the study. Demographic and clinic characteristics were recorded. Before starting the therapy regimens, cerebral blood flow was evaluated by internal carotid artery and middle cerebral artery peak systolic velocity, and pulsatility index measurements via Doppler ultrasonography. Cognitive functions were evaluated by the Standardized Mini-Mental Test. The mean follow-up period was 10.9±2.4 months, ranging between 8 and 16 months. After the follow-up period, the cerebral blood flow, and cognitive function of each woman was re-evaluated. Results Demographic and clinical characteristics of the women were not significantly different between the study groups (P>0.05). There were no significant differences between the pretreatment and posttreatment values for cerebral blood flow indices and cognitive function scores in any of the study groups (P>0.05). Conclusion Different postmenopausal hormone therapy regimens have not revealed any significant effects on either cerebral blood flow or cognitive function.

Background and purpose:Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis.Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis.Experimental approach:Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg−1 s.c.); alendronate (0.003 and 0.03 mg kg−1 s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg−1 s.c.); 17-α-ethinyl oestradiol (0.003 and 0.03 mg kg−1 s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology.Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg−1 s.c.); alendronate (0.003 and 0.03 mg kg−1 s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg−1 s.c.); 17-α-ethinyl oestradiol (0.003 and 0.03 mg kg−1 s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology.Key results:Genistein (10 mg kg−1) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels.Genistein (10 mg kg−1) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels.Conclusions and implications:The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.British Journal of Pharmacology (2008) 155, 896–905; doi:10.1038/bjp.2008.305; published online 11 August 2008The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.British Journal of Pharmacology (2008) 155, 896–905; doi:10.1038/bjp.2008.305; published online 11 August 2008

BACKGROUND: Limited data are available regarding the cost-effectiveness of preventative therapies for postmenopausal women with osteopenia. The objective of the present study was to evaluate the cost-effectiveness of raloxifene, alendronate and conservative care in this population. METHODS: We developed a microsimulation model to assess the incremental cost and effectiveness of raloxifene and alendronate relative to conservative care. We assumed a