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Diabet Med. 2007 Apr 19;
Hadjadj S, Gourdy P, Zaoui P, Guerci B, Roudaut N, Gautier JF, Chabin M, Mauco G, Ragot S; for the RADIAN (Raloxifene in Diabetic Nephropathy) Study Group.
CHU Poitiers, Endocrinology, Poitiers, and INSERM ERM 324, Poitiers, France.
Effect of raloxifene-a selective oestrogen receptor modulator-on kidney function in post-menopausal women with Type 2 diabetes: results from a randomized, placebo-controlled pilot trial.
Aims Epidemiological and experimental data suggest that activation of the oestrogen receptor pathway limits the incidence and the progression of diabetic
nephropathy. We tested the hypothesis that raloxifene protects against increasing urinary albumin excretion in post-menopausal women with Type 2 diabetes in
a randomized pilot clinical trial. Methods We included 39 post-menopausal women with Type 2 diabetes and micro- or macro-albuminuria in a 6-month,
double-blind, placebo-controlled trial: 20 received placebo and 19 received 60 mg raloxifene per day. The albumin : creatinine ratio (ACR) in urine was
determined on three consecutive days during the week before randomization and during the week before the final visit. Results One patient in each group
dropped out in the first 3 weeks, leaving 37 patients for the analysis (19 on placebo and 18 on raloxifene). From randomization to the final visit, mean ACR
was unchanged in the placebo group {277 microg/mg (67; 651) [median (interquartile range)] vs. 284 microg/mg (79; 1508)} but decreased slightly in the
raloxifene group [376 microg/mg (67; 615) vs. 243 microg/mg (103; 549)]. This corresponds to a change of +24 (-37; +517) for the placebo group vs. -10
microg/mg (-36; +16) for the raloxifene group (P = 0.11). In multivariate analysis, raloxifene treatment (P(adjusted) = 0.013), baseline low-density
lipoprotein (LDL) cholesterol (P(adjusted) = 0.023) and change in LDL cholesterol (P(adjusted) = 0.008) were related to the absolute change in ACR. Adverse
effects were similar in the two groups. Conclusions These results suggest that raloxifene may limit the progression of albuminuria in post-menopausal women
with diabetes; further studies in a larger population are warranted.
Endocrinology. 2007 May 3;
Allen MR, Hogan HA, Hobbs WA, Koivuniemi AS, Koivuniemi MC, Burr DB.
Department of Anatomy and Cell Biology and Department of Orthopaedic Surgery, Indiana University School of Medicine, Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis, and Department of Mechanical Engineering,
Raloxifene enhances material-level mechanical properties of femoral cortical and trabecular bone.
We have previously documented that raloxifene enhances the mechanical properties of dog vertebrae independent of changes in bone mass, suggesting a positive
effect of raloxifene on material-level mechanical properties. The goal of this study was to determine the separate effects of raloxifene on the
material-level mechanical properties of trabecular and cortical bone from the femur of beagle dogs. Skeletally mature female beagles (n=12/group) were
treated daily for one year with oral doses of vehicle (VEH) or raloxifene (RAL, 0.50 mg/kg/day). Trabecular bone mechanical properties were measured at the
femoral neck using reduced platen compression, a method that allows the trabecular bone to be tested without coring specimens. Cortical bone properties were
assessed on prismatic beam specimens machined from the femoral diaphysis using both monotonic and dynamic (cyclic relaxation) four-point bending tests.
Trabecular bone from RAL-treated animals had significantly higher ultimate stress (+130%), modulus (+89%) and toughness (+152%) compared to VEH-treated
animals. Cortical bone from RAL-treated animals had significantly greater toughness (+62%) compared to VEH, primarily as a function of increased post-yield
displacement (+100%). There was no significant difference between groups in percent stiffness loss during cortical bone cyclic relaxation tests. These
results are consistent with previous data from the vertebrae of these same animals, showing raloxifene has positive effects on biomechanical properties
independent of changes in bone volume/density. This may help explain how raloxifene reduces osteoporotic fractures despite modest changes in bone mass.
Climacteric. 2007 Jun;10(3):244-8.
Sharma S, Albertazzi P, Bottazzi M.
Centre for Metabolic Bone Disease. Hull. UK.
The long-term effect of raloxifene on the genitourinary tract.
Objective To investigate the effect of long-term treatment with raloxifene on pelvic organ prolapse and urinary incontinence. Methods This was a case-control
study in patients attending the Centre for Metabolic Bone Disease. Eighty-two women were included. The average age was 69 years (range 60-85 years).
Thirty-nine women had taken raloxifene for an average of 55 +/- 25 months and 43 had taken bisphosphonates for an average of 41.96 +/- 15.93 months. The
Prolapse Quality of Life (P-QOL), version 4 and Incontinence Impact questionnaire (IIQ-7) and Urogenital Distress Inventory, short form (UDI-6) were used to
evaluate presence of pelvic organ prolapse and urinary incontinence. Women symptomatic with prolapse were offered a pelvic examination to define the type and
severity of the prolapse. Women giving a history of urinary incontinence were offered urodynamic evaluation to establish the cause of the incontinence. The
main outcome measures were prevalence and severity of pelvic organ prolapse and urinary incontinence and its impact on quality of life. Results Over 50% of
the women complained of incontinence in both groups, 51% (22) of women taking raloxifene and 53% (28) of the controls. Prolapse was present in two women in
the raloxifene group (5%) and six women (11%) in the control group. Urge incontinence was similar in both prevalence (15 vs. 21 women) and severity between
cases and controls. Stress incontinence, on the contrary, had a similar prevalence (20 vs. 19 women) but was more severe in the controls (p = 0.004). There
was no difference in mean scores of IIQ-7 and P-QOL for quality of life between cases and controls. Conclusions Raloxifene taken long-term does not appear to
adversely affect urinary incontinence or prolapse.
Ren Fail. 2007 May;29(4):471-476.
Yanik B, Bavbek N, Yanik T, Inegol I, Kanbay M, Turgut FH, Uz E, Akcay A.
School of Medicine, Physical Medicine and Rehabilitation, Fatih University. Ankara. Turkey.
The Effect of Alendronate, Risedronate, and Raloxifene on Renal Functions, Based on the Cockcroft and Gault Method, in Postmenopausal Women.
Background. Oral alendronate, risedronate, and raloxifene are effective treatment options in the management of postmenopausal osteoporosis. There is little
previously reported about the renal safety profiles of these three agents in osteoporosis. We aimed to assess the risk of renal toxicity associated with oral
alendronate, risedronate, and raloxifene in the treatment of osteoporosis, prospectively. Methods. One hundred and twenty-seven patients with osteoporosis
and osteopenia according to lumbar or femoral-neck bone mineral density t score were enrolled in the study. The patients were randomized to alendronate 70 mg
once weekly (n = 47), risedronate 35 mg once weekly (n = 44), or raloxifene 60 mg per day (n = 36) for one year. Preliminary screening included medical
history, physical examination, lumbar and femoral bone mineral densitometry measurement, and blood biochemical tests, including renal function tests. The
biochemical markers were then assessed at the end of 12 months. Results. There was no significant difference between basal and final renal function
parameters of each group. Also these parameters did not differ between the three groups after 12 months of treatment period. Conclusions. These results
demonstrate that alendronate, risedronate, and raloxifene are all safe drugs for renal functions in the treatment of osteoporosis.
Menopause. 2006 Sep 26;
Yada-Hashimoto N, Nishio Y, Ohmichi M, Hayakawa J, Mabuchi S, Hisamoto K, Nakatsuji Y, Sasaki H, Seino-Noda H, Sakata M, Tasaka K, Murata Y.
From the Department of Obstetrics and Gynecology, School of Medicine, Osaka University, Osaka, Japan.
Estrogen and raloxifene inhibit the monocytic chemoattractant protein-1-induced migration of human monocytic cells via nongenomic estrogen receptor alpha.
OBJECTIVE:: To investigate the effects of estradiol (E2) and raloxifene on the migration of human monocytic THP-1 cells to endothelium. DESIGN:: A prospective comparative study. THP-1 cells, a human acute monocytic leukemia cell line, were used for the study. Migration assays were performed using transwell inserts. THP-1 cells were exposed to E2 or raloxifene in the presence of monocytic chemoattractant protein-1 (MCP-1), a major chemoattractant for monocytes. The cells were transfected with small interfering RNA (siRNA) against estrogen receptor (ER) alpha and ERbeta for gene silencing. ER expression was evaluated by Western blot analysis. RESULTS:: MCP-1 induced the migration of the cells for 90 minutes. The addition of E2 or raloxifene significantly inhibited the MCP-1-induced migration for 90 minutes. Preincubation of THP-1 cells with an ER antagonist, ICI 182780, significantly attenuated the inhibitory effects of E2 and raloxifene. Whereas transfection with siRNA of ERalpha significantly attenuated the inhibition by E2 of MCP-1-induced monocyte migration, transfection with control siRNA or siRNA of ERbeta had no effect on the rapid inhibitory action of E2. Moreover, preincubation of THP-1 cells with a transcriptional inhibitor, actinomycin D, had no effect on the rapid inhibitory action of E2. CONCLUSIONS:: Our findings suggest that both E2 and raloxifene inhibited the MCP-1-induced monocyte migration through nongenomic ERalpha. This result may explain one of the antiatherosclerotic effects of E2 and raloxifene on vasculature.
Neuroimage. 2005 Mar;25(1):63-75. Epub 2005 Jan 12.
Goekoop R, Duschek EJ, Knol DL, Barkhof F, Netelenbos C, Scheltens P, Rombouts SA.
Department of Neurology, VU University Medical Center, De Boelelaan 1117 1081 HV, Amsterdam, The Netherlands.
Raloxifene exposure enhances brain activation during memory performance in healthy elderly males; its possible relevance to behavior.
Raloxifene is a selective estrogen receptor modulator (SERM) that is prescribed in females only, but its use in male subjects is increasingly considered. With a growing number of patients having potential benefit from raloxifene, the need for an assessment of its effects on brain function is growing. Effects of estrogens on brain function are very subtle and difficult to detect by neuropsychological assessment. Functional imaging techniques, however, have been relatively successful in detecting such changes. This study used functional magnetic resonance imaging (fMRI) to examine effects of raloxifene treatment on memory function. Healthy elderly males (n = 28; mean age 63.6 years, SD 2.4) were scanned during performance on a face encoding paradigm. Scans were made at baseline and after 3 months of treatment with either raloxifene (n = 14) or placebo (n = 14). Treatment effects were analyzed using mixed-effects statistical analysis (FSL). Activation during task performance involved bilateral parietal and prefrontal areas, anterior cingulate gyrus, and inferior prefrontal, occipital, and mediotemporal areas bilaterally. When compared to placebo, raloxifene treatment significantly enhanced activation in these structures (Z > 3.1), except for mediotemporal areas. Task performance accuracy diminished in the placebo group (P = 0.02), but remained constant in the raloxifene group (P = 0.60). In conclusion, raloxifene treatment enhanced brain activation in areas spanning a number of different cognitive domains, suggesting an effect on cortical arousal. Such effects may translate into small effects on behavior, including effects on attention and working memory performance, executive functions, verbal skills, and episodic memory. Further neuropsychological assessment is necessary to test the validity of these predictions.
Maturitas. 2005 Mar 14;50(3):182-8.
Kaya H, Ozkaya O, Sezik M, Arslanoglu E, Yilmaztepe A, Ulukaya E.
Department of Obstetrics and Gynecology, School of Medicine, Suleyman Demirel University, Isparta, Turkey.
Effects of raloxifene on serum malondialdehyde, erythrocyte superoxide dismutase, and erythrocyte glutathione peroxidase levels in healthy postmenopausal women.
Objective: To investigate the relationship between raloxifene administration and serum malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx) levels in healthy postmenopausal women. Methods: In a randomized and placebo-controlled design, 80 women received either 60mg/day raloxifene or placebo for 24 weeks. MDA, SOD, and GPx levels were assessed at 0,4,12, and 24 weeks. Wilcoxon signed-rank test and Mann-Whitney U test were used for comparisons. Results: Six women in the treatment arm and eight women in the placebo group discontinued the study. Mean serum MDA levels were significantly (p = 0.001) decreased from 11.4nmol/ml at baseline to 8.9nmol/ml at week 12 with raloxifene treatment. Mean erythrocyte SOD activity was significantly (p = 0.02) reduced from 1472U/gHb at baseline to 1173U/gHb at week 12 following raloxifene administration. Lowered serum MDA and erythrocyte SOD levels persisted during treatment. On contrary, erythrocyte GPx levels did not change significantly with raloxifene administration. Conclusions: Raloxifene (60mg/day) lowers serum MDA levels and erythrocyte SOD activity in postmenopausal women after 12 weeks of treatment. The clinical implications of these findings need to be determined.
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