OBJECTIVES: The present mini review aimed to summarize the existing knowledge regarding the beneficial and adverse effects of raloxifene in menopausal women. METHODS: This study is a review of relevant publications about the effects of raloxifene on sleep disorder, depression, venous thromboembolism, the plasma concentration of lipoprotein, breast cancer, and cognitive function among menopausal women. RESULTS: Raloxifene showed no significant effect on depression and sleep disorder. Verbal memory improved with administration of 60 mg/day of raloxifene while a mild cognitive impairment risk reduction by 33% was observed with administration of 120 mg/day of raloxifene. Raloxifene was associated with a 50% decrease in the need for prolapse surgery. The result of a meta-analysis showed a significant decline in the plasma concentration of lipoprotein in the raloxifene group compared to placebo (standardized mean difference, −0.43; 10 trials). A network meta-analysis showed that raloxifene significantly decreased the risk of breast cancer (relative risk, 0.572; 95% confidence interval, 0.327–0.881; P = 0.01). In terms of adverse effects of raloxifene, the odds ratio (OR) was observed to be 1.54 (P = 0.006), indicating 54% increase in the risk of deep vein thrombosis (DVT) while the OR for pulmonary embolism (PE) was 1.05, suggesting a 91% increase in the risk of PE alone (P = 0.03). CONCLUSIONS: Raloxifene had no significant effect on depression and sleep disorder but decreased the concentration of lipoprotein. Raloxifene administration was associated with an increased risk of DVT and PE and a decreased risk of breast cancer and pelvic organ prolapse in postmenopausal women.
Breast Neoplasms ; Cognition ; Depression ; Female ; Humans ; Lipoproteins ; Memory ; Mild Cognitive Impairment ; Odds Ratio ; Pelvic Organ Prolapse ; Plasma ; Prolapse ; Pulmonary Embolism ; Raloxifene Hydrochloride ; Risk Reduction Behavior ; Sleep Wake Disorders ; Venous Thromboembolism ; Venous Thrombosis

The author and author's affiliation should be corrected.
Bone Density* ; Endometriosis* ; Female ; Gonadotropin-Releasing Hormone* ; Humans ; Raloxifene Hydrochloride*

OBJECTIVES: To evaluate and compare the efficacy and safety of the combination of raloxifene and alendronate with those of monotherapies in elderly women with osteoporosis. METHODS: Sixty-two postmenopausal women (mean age 63.5 ± 0.5 years) attending gynecologic osteoporosis clinics with established osteoporosis were randomly allocated to one of four treatment groups and monitored for 3 years. All patients enrolled in this study, including those in the control group (n = 14), received 1.0 g elemental calcium and 400 units of vitamin D per day. The raloxifene group (n = 16) received raloxifene 60 mg (Evista®) per day; alendronate group (n = 17) received low-dose (5 mg) alendronate with calcitriol 0.5 µg (Maxmarvil®) per day; and the combination therapy group (n = 15) received both raloxifene 60 mg and low-dose (5 mg) alendronate with calcitriol 0.5 µg. Bone mineral density (BMD) was measured in the lumbar spine and hip before and after 3 years of treatment. RESULTS: In patients who received the combined therapy, BMD increased in the lumbar spine and the hip by 7.2% (P<0.001) and 4.8% (P<0.001) at 3 years. For patients in the alendronate group, the increases were 6.7% (P<0.001) and 3.1% (P<0.01) respectively, for the raloxifene group, the increases were 4.36% (P<0.001) and 1.9% (P<0.05) in the vertebrae and femora, respectively; however, the BMD of patients in the control group decreased by 1.81% (P<0.05) and 1.6% (P<0.05), respectively, after 3 years. Patients who received the combination therapy had significantly higher BMD in both the vertebrae femora (P<0.01) in comparison to that in those treated with raloxifene or alendronate individually. CONCLUSIONS: This 3-year randomized study showed the improved effects of alendronate and raloxifene combination on spine and hip BMD in elderly postmenopausal women with established osteoporosis.
Aged* ; Alendronate* ; Bone Density ; Calcitriol ; Calcium ; Female ; Hip ; Humans ; Osteoporosis* ; Raloxifene Hydrochloride* ; Spine ; Vitamin D

OBJECTIVE: Bisphosphonate, a typical bone resorption inhibitor, is an important first-line drug for treating osteoporosis. Recent studies show a novel paradigm in stimulating bone formation. Teriparatide, which is composed of recombinant human parathyroid hormone, stimulates osteoblasts and induces bone regeneration. Bone mineral density (BMD) that was used before and after the treatment with anti-osteoporosis drug was compared for the effectiveness in therapy between a combination of teriparatide and selective estrogen receptor modulator (SERM), and bisphosphonate. METHODS: We retrospectively reviewed the outcomes of 85 postmenopausal women who were concurrently diagnosed with osteoporosis and spinal compression fracture between November 2008 and January 2015. The targeted group were treated with teriparatide and SERM (TS group, n=26) and bisphosphonate (B group, n=59). RESULTS: In both groups, BMD of femur neck was not improved after the medication. In the TS group, on the other hand the BMD and T-score of lumbar spine has significantly improved. BMD ratio of lumbar spine was prominently higher than those of TS group. CONCLUSION: The combination therapy of teriparatide and SERM was very effective in treating the lumbar spine, compared to that of bisphosphonate. Although the period of teriparatide treatment has been relatively short, the preventive effects of compression fracture were considerable. Thus, combination therapy of teriparatide and SERM is highly recommended for patients who are concerned with spinal compression fracture from osteoporosis.
Bone Density ; Bone Regeneration ; Bone Resorption ; Female ; Femur Neck ; Fractures, Compression* ; Hand ; Humans ; Osteoblasts ; Osteogenesis ; Osteoporosis* ; Parathyroid Hormone ; Postmenopause ; Raloxifene Hydrochloride* ; Retrospective Studies ; Selective Estrogen Receptor Modulators ; Spine ; Teriparatide*

Selective estrogen receptor modulators (SERMs) are now being used as a treatment for breast cancer, osteoporosis and postmenopausal symptoms, as these drugs have features that can act as an estrogen agonist and an antagonist, depending on the target tissue. After tamoxifen, raloxifene, lasofoxifene and bazedoxifene SERMs have been developed and used for treatment. The clinically decisive difference among these drugs (i.e., the key difference) is their endometrial safety. Compared to bisphosphonate drug formulations for osteoporosis, SERMs are to be used primarily in postmenopausal women of younger age and are particularly recommended if there is a family history of invasive breast cancer, as their use greatly reduces the incidence of this type of cancer in women. Among the above mentioned SERMs, raloxifene has been widely used in prevention and treatment of postmenopausal osteoporosis and vertebral compression fractures, and clinical studies are now underway to test the comparative advantages of raloxifene with those of bazedoxifene, a more recently developed SERM. Research on a number of adverse side effects of SERM agents is being performed to determine the long-term safety of this class of compouds for treatment of osteoporosis.
Breast Neoplasms ; Chemistry, Pharmaceutical ; Estrogens ; Female ; Fractures, Compression ; Humans ; Incidence ; Osteoporosis ; Osteoporosis, Postmenopausal ; Raloxifene Hydrochloride ; Selective Estrogen Receptor Modulators* ; Tamoxifen

The objectives of this article are to review current pharmacologic approaches for the treatment of osteoporosis in Korea. Calcium and vitamin D supplementation are necessary for osteoporotic patients with inadequate calcium intake and low vitamin D nutritional status, which is a risk factor of osteoporosis. Several pharmacologic therapies are available for treatment of osteoporosis. Antiresorptive agents, bisphosphonates, selective estrogen receptor modulators, denosumab, estrogens, and tibolone are the basis of therapy. Antiresorptive medications reduce the rates of bone remodeling. Several drugs have shown their ability to reduce vertebral and/or nonvertebral fractures in patients with osteoporosis. Bisphosphonates that reduced bone loss and fragility are usually the mainstay of the treatment of osteoporosis. The recently registered denosumab shows similar anti-fracture efficacy by neutralizing receptor activator of nuclear factor-κB ligand, however, marked differences in reversibility can be observed between the two drugs. The anabolic agents, teriparatide, stimulates new bone formation, increases bone density, and reduces fractures. Other treatment options such as hormone replacement therapy, tibolone, raloxifene, and bazedoxifene are also reviewed in this article. Pharmacologic treatments of osteoporosis are associated with adverse effects, but the benefits generally far surpass the risks.
Anabolic Agents ; Bone Density ; Bone Density Conservation Agents ; Bone Remodeling ; Calcium ; Denosumab ; Diphosphonates ; Estrogens ; Hormone Replacement Therapy ; Humans ; Korea ; Nutritional Status ; Osteogenesis ; Osteoporosis* ; Raloxifene Hydrochloride ; Risk Factors ; Selective Estrogen Receptor Modulators ; Teriparatide ; Vitamin D

BACKGROUND: To assess the cost-effectiveness of drug therapy to prevent osteoporotic fractures in postmenopausal women with osteopenia in Korea. METHODS: A Markov cohort simulation was conducted for lifetime with a hypothetical cohort of postmenopausal women with osteopenia and without prior fractures. They were assumed to receive calcium/vitamin D supplements only or drug therapy (i.e., raloxifene or risedronate) along with calcium/vitamin D for 5 years. The Markov model includes fracture-specific and non-fracture specific health states (i.e. breast cancer and venous thromboembolism), and all-cause death. Published literature was used to determine the model parameters. Local data were used to estimate the baseline incidence rates of fracture in those with osteopenia and the costs associated with each health state. RESULTS: From a societal perspective, the estimated incremental cost-effectiveness ratios (ICERs) for the base cases that had T-scores between -2.0 and -2.4 and began drug therapy at the age of 55, 60, or 65 years were $16,472, $6,741, and -$13,982 per quality-adjusted life year (QALY) gained, respectively. Sensitivity analyses for medication compliance, risk of death following vertebral fracture, and relaxing definition of osteopenia resulted in ICERs reached to $24,227 per QALY gained. CONCLUSIONS: ICERs for the base case and sensitivity analyses remained within the World Health Organization's willingness-to-pay threshold, which is less than per-capita gross domestic product in Korea (about $25,700). Thus, we conclude that drug therapy for osteopenia would be a cost-effective intervention, and we recommend that the Korean National Health Insurance expand its coverage to include drug therapy for osteopenia.
Bone Diseases, Metabolic* ; Breast Neoplasms ; Cohort Studies ; Cost-Benefit Analysis ; Drug Therapy ; Female ; Global Health ; Gross Domestic Product ; Humans ; Incidence ; Korea ; Medication Adherence ; National Health Programs ; Osteoporotic Fractures* ; Postmenopause ; Quality-Adjusted Life Years ; Raloxifene Hydrochloride ; Risedronate Sodium

OBJECTIVES: To evaluate the efficacy of raloxifene in preventing bone loss associated with long term gonadotropin-releasing hormone agonist (GnRH-a) administration. METHODS: Twenty-two premenopausal women with severe endometriosis were treated with leuprolide acetate depot at a dosage of 3.75 mg/4 weeks, for 48 weeks. Bone mineral density (BMD) was evaluated at admission, and after 12 treatment cycles. RESULTS: At cycle 12 of GnRH-a plus raloxifene treatment, lumbar spine, trochanter femoral neck, and Ward's BMD differed from before the treatment. A year after treatment, the lumbar spine and trochanter decreased slightly, but were not significantly different. CONCLUSIONS: Our study shows that the administration of GnRH-a plus raloxifene in pre-menopausal women with severe endometriosis, is an effective long-term treatment to prevent bone loss.
Bone Density* ; Endometriosis* ; Female ; Femur ; Femur Neck ; Gonadotropin-Releasing Hormone* ; Humans ; Leuprolide ; Raloxifene Hydrochloride* ; Spine

BACKGROUND: Epidemiology studies suggest that oral bisphosphonate may increase the risk of esophageal cancer. The present study aimed to investigate the association between exposure of oral bisphosphonate and risk of esophageal cancer. METHODS: Using the nationwide medical claim database in South Korea, 2,167,955 subjects, who initiated osteoporosis treatment (oral bisphosphonate, intravenous bisphosphonate or raloxifene) or performed dual energy X-ray absorptiometry (DXA) between 2008 and 2012, were analyzed. Diagnosis of esophageal cancer was estimated from medical claim database. Standardized incidence ratio (SIR) was estimated by comparing with incidence in the general population. Cox proportional hazards modeling was used to investigate age-adjusted hazard ratio (aHR) of esophageal cancer. RESULTS: The present study included oral bisphosphonate group (N=1,435,846), comparator group 1 (intravenous bisphosphonate or raloxifene, N=78,363) and comparator group 2 (DXA, N=653,746). Mean age was 65.6+/-8.8 years and mean observation duration was 30.9+/-17.7 months. During 5,503,688 patient-years, 205 esophageal cancer incidences were observed. The annual incidence of esophageal cancer was 3.88, 4.21, and 3.30 for oral bisphosphonate group, comparator group 1 and comparator group 2, respectively. SIR of esophageal cancer was 1.24, 1.38, and 1.40 for oral bisphosphonate group, comparator group 1 and comparator group 2, respectively. Esophageal cancer risk of oral bisphosphonate group was not significantly different from comparator group 1 and comparator group 2 (aHR 0.87; 95% confidence interval [CI] 0.39-1.98 and aHR 0.94; 95% CI 0.68-1.30, respectively). CONCLUSIONS: The use of oral bisphosphonate was not associated with increased risk of esophageal cancer in real clinical practice using large scale nationwide database.
Absorptiometry, Photon ; Diagnosis ; Epidemiology ; Esophageal Neoplasms* ; Incidence ; Korea ; Osteoporosis ; Proportional Hazards Models ; Raloxifene Hydrochloride

Selective estrogen receptor modulators (SERMs) are a diverse group of synthetic non-steroidal compounds that have various levels of estrogen receptor (ER) agonist or antagonist activity depending on the target tissue. This feature of SERMs could be explained by the differential expression of two ER isoforms (ERalpha or ERbeta), the differential ER conformational change and the differential coregulatory proteins (coactivator or corepressor) in a selected tissue. Based on their efficacy and safety, SERMs have been used for the prevention and treatment of breast cancer (tamoxifene and toremifene), prevention and treatment of osteoporosis (relaoxifene and bazedoxifene), treatment for dyspareunia related to vulvovaginal atrophy (ospemifene) and treatment for vasomotor symptoms associated with menopause (tissue selective estrogen complex; TSEC). Many of the available SERMs are well-known for their anti-estrogenic effects in breast and for their estrogenic effects in bone. The effect on the endometrium have played a key role in differentiate SERMs in clinical practice. The effect of SERMs in the vagina also shows clear distinction among different SERMs. This review summarizes their action mechanism and describes their clinical findings in different target tissues. In the osteoporosis treatment, SERMs such as raloxifene and bazedoxifene is a safe and effective option for women who cannot tolerate or are unwilling to take bisphosphonates and may be appropriate for younger woman with the age of < or =70 years old who expect to remain on therapy for many years and are concerned about the long-term safety of bisphosphonates.
Atrophy ; Breast ; Breast Neoplasms ; Diphosphonates ; Dyspareunia ; Endometrium ; Estrogens ; Female ; Humans ; Menopause ; Osteoporosis ; Protein Isoforms ; Raloxifene Hydrochloride ; Selective Estrogen Receptor Modulators ; Vagina