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PubMed2003

Effects of raloxifene on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis.

BACKGROUND: Premature amenorrhea and hypoestrogenism and lack of hormone replacement therapy after menopause have been frequently reported in uremic women on dialysis. Therefore, in addition to renal osteodystrophy, postmenopausal women on dialysis could be at risk of osteoporosis. In addition, these patients are at higher risk for hyperlipidemia, arteriosclerosis, and subsequent coronary heart disease and stroke. Recent evidence has suggested that hormone replacement therapy (HRT) in postmenopausal women could have several beneficial effects as well as potentially serious risks. Great efforts have been made to identify therapeutic alternatives that would have the benefits of estrogen on brain and bone without its adverse effects on breast and endometrium. In the present study, we evaluated the effect of raloxifene, a selective estrogen receptor modulator (SERM), on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis. METHODS: We performed a prospective, blind, placebo-controlled, and randomized study. Fifty postmenopausal women on chronic hemodialysis with proven severe osteopenia or osteoporosis by bone densitometry were selected. After a written informed consent, patients were randomized into two groups: 25 women on placebo and 25 women on the study drug, raloxifene hydrochloride, at a dose of 60 mg/day. In all patients, we performed a baseline bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, serum lipids (total low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol and triglycerides) and serum markers of bone resorption (pyridinoline crosslinks). BMD was reassessed after 1 year of therapy. Bone resorption markers were determined every 3 months for 1 year. RESULTS: After 1 year on raloxifene therapy, lumbar spine BMD (trabecular bone) significantly improved, whereas femoral neck BMD (cortical bone) did not change significantly. No changes in BMD were observed at trabecular or cortical sites in the placebo group. Serum pyridinoline levels showed a significant decrease after 6 months on raloxifene that persisted thereafter. Low-density lipoprotein (LDL)-cholesterol decreased significantly in the raloxifene group with no changes in serum triglycerides, total cholesterol, or HDL cholesterol. No significant side effects were observed in the raloxifene group. CONCLUSION: The study demonstrates that after one year on raloxifene, postmenopausal women on hemodialysis have a significant increase in trabecular BMD, decrease in bone resorption markers and LDL-cholesterol values, suggesting that SERMs could constitute a therapeutic alternative to improve bone metabolism and control of hyperlipidemia in these patients. The possible long-term effects of raloxifene remain to be determined.

Aged↗
PubMed2004

Effects of 17beta-estradiol, tamoxifen and raloxifene on the protein and mRNA expression of interleukin-6, transforming growth factor-beta1 and insulin-like growth factor-1 in primary human osteoblast cultures.

We investigated the effects of 17betaestradiol and two selective estrogen receptor modulators, tamoxifen and raloxifene, on the expression and release of constitutive and interleukin-1-stimulated interleukin (IL)-6, transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 by osteoblasts in primary culture from trabecular bone of healthy post-menopausal women. After 24 h incubation with 10(-8) M concentration of these compounds, there was no decrease in: a) the constitutive or IL-1beta-induced levels of IL-6 protein released to culture medium; b) the constitutive IL-6 mRNA expression after incubation of osteoblasts with 10(-8) M 17betaestradiol or 10(-8) M tamoxifen for 1, 3, 6, 24 or 30 h. Although a decrease after 30 h of treatment with 10(-8) M, raloxifene was found in mRNA IL-6 expression, and this fact was not reflected by a decrease in the release of IL-6 protein to the culture medium after 48 h of incubation with 10(-8) M or 10(-7) M raloxifene. Tumoral growth factorTGF-betal expression was not influenced by incubation with these compounds. Gene expression of IGF-I increased following 24 or 30 h incubation with 10(-8) M 17beta-estradiol and 30 h incubation with raloxifene. Tamoxifen did not affect IGF-I expression. In conclusion, the effects of estradiol or tamoxifen on bone metabolism do not appear to be mediated through the regulation of osteoblast IL-6 release or synthesis, but raloxifene produces a decrease in mRNA IL-6 expression. The actions of estradiol, tamoxifen and raloxifene do not appear to be mediated by tumoral growth factor TGF-beta1. On the other hand, an increase in IGF-I synthesis induced by raloxifene and estradiol could mediate, in part, the effects of these compounds on bone.

Aged↗
PubMed2005

Tamoxifen treatment of bleeding irregularities associated with Norplant use.

OBJECTIVES: To evaluate the possible role of tamoxifen (selective estrogen receptor modulators, SERM) in treating bleeding irregularities associated with Norplant contraceptive use. MATERIAL AND METHODS: Randomized clinical trial including 100 Norplant users complaining of vaginal bleeding irregularities. The trial was conducted in the Family Planning Clinic of Assiut University Hospital. Women were assigned at random to receive tamoxifen tablets (10 mg) twice daily for 10 days or similar placebo. Women were followed-up for 3 months. The end points were percentage of women who stopped bleeding during treatment, bleeding/spotting days during the period of follow-up, effect of treatment on their lifestyle, and side effects and discontinuation of contraception. RESULTS: There was good compliance with treatment. At the end of treatment, a significantly higher percentage of tamoxifen users stopped bleeding in comparison to the control group (88% vs. 68%, respectively; p=.016). Women who used tamoxifen had significantly less bleeding and/or spotting days than women who used placebo, during the first and second months. During the third month, there were no significant differences between the two groups. Women who used tamoxifen reported improvement in performing household activities, religious duties and in sexual life, during the first 2 months. In the third month, there were no differences between the two groups. There were no significant differences between tamoxifen and placebo groups in reporting side effects. In the group who used tamoxifen, two women discontinued Norplant use because of bleeding vs. nine women in the placebo group. CONCLUSION: Tamoxifen use at a dose of 10 mg twice daily orally, for 10 days, has a beneficial effect on vaginal bleeding associated with Norplant use. In addition, the bleeding pattern was better in women who used tamoxifen for the following 2 months after treatment. However, these results have to be confirmed in a larger trial before advocating this line of treatment.

Adult↗
PubMed2005

Raloxifene treatment enhances brain activation during recognition of familiar items: a pharmacological fMRI study in healthy elderly males.

Raloxifene is a selective estrogen receptor modulator that may delay the onset of mild cognitive impairment in elderly women. Effects of raloxifene treatment on mental performance in males remain to be investigated. In a previous functional magnetic resonance imaging (fMRI) study, we showed that raloxifene treatment enhanced brain activation in elderly males during encoding of new information (faces) into memory. The current study used fMRI in the same group of subjects to screen for effects of raloxifene treatment on brain function during face recognition. Healthy elderly males (n=28; mean age 63.6 years, SD 2.4) were scanned at baseline and after 3 months of treatment with either raloxifene 120 mg (n=14) or placebo (n=14) in a randomized, double-blind, placebo-controlled study design. Functional data were analyzed in an event-related fashion with respect to correct hits and correct rejections using FSL software. Performance data were analyzed with respect to recognition accuracy, latency, and response bias. Functional effects of treatment were found on brain activation related to correct hits only. When compared to placebo treatment, raloxifene treatment enhanced brain activation in the left posterior parahippocampal area (Z=3.9) and right inferior prefrontal cortex (Z=3.5). Recognition accuracy scores remained stable in the raloxifene group, whereas the placebo group showed a small but significant decrease in accuracy scores (p=0.02). No significant effects were found on response bias or latency. In conclusion, raloxifene treatment affects brain function during memory performance in a way that may reflect increased arousal during initial encoding, with downstream effects on brain function during retrieval of information. Behaviorally, such neurofunctional effects may actively block decreased memory performance as a result of context-dependency. The validity of these predictions can be tested in large-scale clinical trials.

Aged↗
PubMed2005

Estrogen receptor (ER) beta modulates ERalpha-mediated transcriptional activation by altering the recruitment of c-Fos and c-Jun to estrogen-responsive promoters.

In this study, an estrogen receptor (ER) alpha-expressing T47D cell line containing an inducible tet-off FLAG-ERbeta was used to examine the influence of ERbeta on ERalpha activity. Real-time PCR analysis of mRNA levels of two well-studied estrogen-responsive genes, pS2 and progesterone receptor (PR), showed that the expression levels of both genes were reduced in the presence of ERbeta. Chromatin immunoprecipitation assays showed that the 17beta-estradiol (E2)-induced recruitment patterns to the pS2 and PR promoters were similar for both ERalpha and ERbeta. ERbeta expression did not significantly influence the kinetic recruitment profile of ERalpha to the pS2 promoter, but it was evident that ERalpha occupancy at the PR promoter was reduced. The E2-induced recruitment of c-Fos to a 12-O-tetradecanoylphorbol-13-acetate response element site in the PR promoter was significantly reduced in the presence of ERbeta, whereas only a slight reduction in the recruitment of c-Fos to the pS2 promoter was observed. ERbeta expression resulted in a significant reduction in the E2-induced expression of c-Fos mRNA. The recruitment pattern of c-Jun was also altered by ERbeta, although the expression levels of c-Jun were not. Expression of ERbeta caused a further 30-50% decrease of the E2-induced reduction in ERalpha protein after 3 h of E2 treatment, showing that ERbeta influences ERalpha protein levels. The altered recruitment of the activating protein-1 complex, combined with the reduction in ERalpha protein levels, may partly explain the antagonistic effect of ERbeta on ERalpha-mediated transcription.

Cell Line↗
PubMed1999

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.

CONTEXT: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. OBJECTIVE: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. DESIGN: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. INTERVENTIONS: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. MAIN OUTCOME MEASURES: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. RESULTS: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

Adult↗
PubMed1999

Special considerations in breast cancer risk and survival.

Experimental and clinical evidence suggests that breast neoplasia appears to be a hormone-dependent process that may also be influenced by dietary factors in many women. Conflicting reports on the relationship between exogenous hormones and the development, progression, and recurrence of breast cancer are critically examined in this report. The absolute breast cancer risk associated with either hormone replacement therapy or oral contraceptive use has not been clearly defined. Data from some large prospective studies have actually documented lower mortality rates for women taking hormone replacement compared with those for women who did not have hormone replacement therapy. In this regard, age, duration of use, and preexisting breast cancer risk factors must be taken into account. Although the results of two major prospective clinical trials addressing the role of timing of surgery within the menstrual cycle are forthcoming, the majority of studies have found no consistent association between timing of surgery and breast cancer survival. Recently reported prospective randomized data showing that selective-estrogen-receptor-modulators can act as effective chemoprevention agents in women at increased risk for breast cancer development are presented. Finally, information regarding the effect of dietary manipulation on breast cancer risk and survival is reviewed.

Breast Neoplasms↗
PubMed2000

Absolute structure determination of the highly biologically active bisdehydrodoisynolic acids.

In a project designed to relate the unexpected in vivo and in vitro properties exhibited by (+)- and (-)-bisdehydrodoisynolic acid with their absolute stereochemical structure, an X-ray crystal-structure analysis was undertaken of the highly estrogenic, poorly binding (-) enantiomer. (1) and (13)C NMR spectra are also reported for the first time. The crystal structure shows the cis juxtaposition of the carboxyl and ethyl groups, which are separated by a large torsion angle, and that only the carbon atom holding the carboxyl group is out of the plane in which the remainder of the fused three-ring moiety lies. The crystal structure, which unequivocally characterizes the (-) enantiomer as cis-13(S),14(R) and, implicitly, the (+) enantiomer as cis-13(R),14(S), will be useful in continued studies aimed at explaining the selective estrogen receptor modulation (SERM) of these enantiomers which, in some cases, produces significantly different end-organ effects compared to those of estradiol, in both males and females, affording the promise of a variety of therapeutic and pharmacologic applications.

Crystallography, X-Ray↗
PubMedDate not supplied

Antiestrogens.

Explore the source record for details and available documents.

Estrogen Antagonists↗
PubMed2003

Diagnosis and management of treatment-related osteoporosis in men with prostate carcinoma.

Osteoporosis is a complication of androgen deprivation therapy in men with prostate carcinoma. Androgen deprivation therapy, caused by either bilateral orchiectomy or treatment with a gonadotropin-releasing hormone agonist, decreases bone mineral density and increases fracture risk. Other factors including diet and lifestyle may contribute to bone loss. There is limited information regarding the best strategy to prevent osteoporosis in men with prostate carcinoma. Lifestyle modification including smoking cessation, moderation of alcohol consumption, and regular weight-bearing exercise should be encouraged. Supplemental calcium and vitamin D are also recommended. Additional treatment may be warranted for men with osteoporosis, fractures, or high rates of bone loss during androgen deprivation therapy. Intravenous pamidronate, a second-generation bisphosphonate, prevents bone loss during androgen deprivation therapy. Zoledronic acid, a more potent third-generation bisphosphonate, not only prevents bone loss but also increases bone mineral density during androgen deprivation therapy. Other bisphosphonates may be effective although they have not been evaluated in this clinical setting. Treatment with estrogens or selective estrogen receptor modulators may also be effective. Monotherapy with bicalutamide or other antiandrogens may cause less bone loss than androgen deprivation therapy.

Absorptiometry, Photon↗
PubMed2003

Favorable cardiac risk among elderly breast carcinoma survivors.

BACKGROUND: There are two reasons why women who survive breast carcinoma may be at a lower risk of developing coronary heart disease (CHD) compared with women without a history of breast carcinoma. First, estrogens may be etiologic in the development of breast carcinoma and protective of CHD. Second, a common therapy for breast carcinoma (tamoxifen) may be associated with cardiac protection. METHODS: In this population-level cohort study, the authors analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-Medicare program to study the cardiac risk of elderly female Medicare beneficiaries with and without a history of breast carcinoma. Using the SEER file, the authors identified elderly women survivors of Stage 0, I, or II breast carcinoma (n = 5980) diagnosed between the ages of 55 and 64. Using the Medicare 5% noncancer file, the authors also identified elderly women without a history of cancer (n = 23,165). They followed women from age 67 for up to 5 years for hospitalization for acute myocardial infarction (AMI) through a review of Medicare claims. The authors controlled the analyses for race, socioeconomic status, geographic location, cohort entry year, and medical comorbidity. RESULTS: The hazard of hospitalization for AMI for breast carcinoma survivors relative to comparison patients was 0.66 (95% confidence interval, 0.49-0.88). This apparent cardioprotective effect of breast carcinoma survivorship was stronger in breast carcinoma survivors with documented cardiac risk factors. CONCLUSIONS: Survivors of early-stage postmenopausal breast carcinoma are at a significantly lower risk of hospitalization for AMI than women who do not have a history of breast carcinoma. That survivors' risk varies with previous cardiac risk factors may be consistent with effects of selective estrogen receptor modulators. This phenomenon should be evaluated further with individual-level data containing information on patient cardiac risk factors and tamoxifen use to help clarify the mechanism behind the risk reduction.

Aged↗
PubMed2003

Antiestrogens are pro-apoptotic in normal human breast epithelial cells.

Estrogens promote cell proliferation in normal and transformed mammary epithelial cells by inducing expression of hormone-responsive genes involved in the cell cycle. The action of antiestrogens is therefore central in regard to their potent inhibitory effects on estrogen-induced cell growth. We used normal human epithelial breast cells from primary cultures (HBE cells) to study hormonal (estrogen and antiestrogen) regulation on 3 key proteins involved in the apoptotic process: Bcl-2, p53 and caspase-3. The mammary adenocarcinoma cell line, MCF-7, was also used to study the molecular regulation of Bcl-2. In both HBE and MCF-7 cells, we found that estradiol (E2) induced an increase in Bcl-2 mRNA levels. This effect was counteracted in the presence of a pure antiestrogen, ICI 182780 (ICI). Alone, ICI did not modify either the Bcl-2 protein or mRNA levels in HBE cells, whereas in MCF-7, a strong downregulation of Bcl-2 mRNA was observed. In parallel, in HBE cells, we observed that E2 caused a decrease in p53 and caspase-3 protein levels, whereas ICI alone increased p53 and caspase-3 protein levels. The ICI effects on p53 and caspase-3 were partially counteracted by E2. Under the same experimental conditions, ICI exerts a potent pro-apoptotic effect, which was not counteracted by E2. In contrast, 4-hydroxytamoxifen was slightly weaker as a pro-apoptotic agent in HBE cells and its effects were reversed by E2. We demonstrate that in HBE cells, ICI reverses the anti-apoptotic action of E2 and alone acts as a highly potent pro-apoptotic molecule. These results provide new insight into treatment for breast cancer prevention.

Adenocarcinoma↗
PubMed2003

Polymorphic variation at the -202 locus in IGFBP3: Influence on serum levels of insulin-like growth factors, interaction with plasma retinol and vitamin D and breast cancer risk.

Previous reports have suggested an association between circulating IGFBP-3 levels and the risk of premenopausal breast cancer, and a single nucleotide polymorphism (SNP) in the promoter region of IGFBP-3 (nucleotide -202) was shown to influence transcription. There is prior evidence that the action of antiproliferative agents such as retinoids and selective estrogen receptor modulators (SERMs) act in part by upregulating IGFBP3 gene expression. We identified 677 women with incident breast cancer and 834 matched controls from the Nurses' Health Study (NHS) and genotyped them at the -202 locus. For 943 of these women, we had previously measured IGF-I and IGFBP-3 plasma levels, and for 861 of these subjects, plasma retinol levels were available. Age-adjusted mean circulating IGFBP-3 levels were highest in the individuals with the AA genotype and decreased significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4,426 ng/ml, 4,060 ng/ml and 3,697 ng/ml, respectively). We found a positive relation between age-adjusted IGFBP-3 levels and plasma retinol (14% difference in IGFBP-3 in top vs. bottom tertiles of retinol, p for trend < 0.001; Spearman correlation coefficient r = 0.25), which was similar across genotypes at the -202 IGFBP3 locus (interaction term, F = 0.10, p = 0.91). Breast cancer risk was not significantly related to genotype at the -202 locus in our prospective analyses. We confirmed a relation between the -202 IGFBP3 polymorphism and IGFBP-3 serum levels and observed a positive correlation between circulating retinol levels and circulating IGFBP-3 levels, providing further evidence that retinoids may influence IGF physiology. Our data do not demonstrate a significant influence of this locus on breast cancer risk, but we cannot exclude a minor influence or an influence confined to subgroups.

Adult↗
PubMed2006

Leptin--from regulation of fat metabolism to stimulation of breast cancer growth.

Leptin restricts intake of calories as a satiety hormone. It probably stimulates neoplastic proliferation in breast cancer, too. Growth of malignant cells could be regulated by various leptin-induced second messengers like STAT3 (signal transducers and activators of transcription 3), AP-1 (transcription activator protein 1), MAPK (mitogen-activated protein kinase) and ERKs (extracellular signal-regulated kinases). They seem to be involved in aromatase expression, generation of estrogens and activation of estrogen receptor alpha (ERalpha) in malignant breast epithelium. Leptin may maintain resistance to antiestrogen therapy. Namely, it increased activation of estrogen receptors, therefore, it was suspected to reduce or even overcome the inhibitory effect of tamoxifen on breast cell proliferation. Although several valuable reviews have been focused on the role of leptin in breast cancer, the status of knowledge in this field changes quickly and our insight should be continuously revised. In this summary, we provide refreshed interpretation of intensively reported scientific queries of the topic.

Animals↗
PubMed2003

Assessment of bone mineral density in adults and children with Marfan syndrome.

Recent studies indicate that decreased bone mineral density (BMD) occurs in the spine, femoral necks and greater trochanters of some adults and children with Marfan syndrome. Because there is uncertainty regarding the BMD status of patients with Marfan syndrome, we undertook an analysis of BMD in both adults and children with Marfan syndrome. Dual energy X-ray absorptiometry analysis was performed on a convenience sample of 51 patients (30 adults and 21 children) with diagnosed Marfan syndrome from 1993 to 2000. T-Scores (i.e. the number of standard deviations above or below the average normal peak bone density) were determined for comparison of adults. Mean+/-SD of individual BMD values were used for comparison of the data of children. Compared to standard values obtained from normal adult patients, adult males with Marfan syndrome demonstrated significantly reduced femoral neck BMD with an average T-score of -1.54 ( P<0.001), diagnostic of osteopenia. Although osteopenia and osteoporosis were observed in several middle aged and pre- and postmenopausal women, the average T-score value for adult females and children were within normal limits. The etiology and full significance of decreased BMD in adult male patients with Marfan syndrome remain uncertain at the present time. Our results lead us to question the value of aggressive BMD evaluations by DXA in these patients, particularly prior to reaching mid-age. Further investigations will be required to shed insights into the natural history of BMD in adults and children with Marfan syndrome. Any application of bone mineral replacement therapy such as bisphosphonate, selective estrogen receptor modulators, hormone replacement therapy and vitamin D in these patients may be premature based on the existing evidence.

Absorptiometry, Photon↗
PubMed2005

The effect of a fracture protocol on hospital prescriptions after minimal trauma fractured neck of the femur: a retrospective audit.

Effective therapies for the treatment of osteoporosis and fracture have been available for a number of years. Despite this, there are numerous reports indicating very low uptake rates in those admitted to hospital with fracture. The aim of this retrospective audit was to assess the impact of a fracture protocol on inpatient prescriptions of osteoporosis therapy. A fracture protocol was arrived at by consensus and was based on recommendations from the Australian Fracture Prevention Summit, which included specific advice on the commencement in hospital of calcium, vitamin D, synthetic estrogen receptor modulators (SERMs) and bisphosphonates. We studied subjects who were treated for fractured neck of the femur at Royal Hobart Hospital from March 2002 to March 2004 and included 161 prior to the start of the protocol and 93 after. As compared to the baseline period, subjects after the introduction of the protocol had higher rates of in-hospital prescription for any treatment (58 vs. 36%, P <0.01), calcium (51 vs. 26%, P <0.01), vitamin D (48 vs. 29%, P <0.01) and oral bisphosphonates (24 vs. 5%, P <0.01), but not SERMs as expected (1 vs. 1%, P =0.70). Additional factors affecting the decision to start any treatment included in-hospital death (OR 0.16, 95% CI 0.05-0.49), dementia (OR 0.39, 95% CI 0.21-0.74), a trend for female sex (OR 1.79, 95%CI 0.96-3.36), but not age. In conclusion, a structural approach to changing hospital policy from the top down is effective at substantially increasing the usage of effective therapy after fractured neck of the femur.

Aged↗