Raloxifene/Vitamin D Combination Therapy vs. Raloxifene Monotherapy on Serum 25-Hydroxy- Vitamin D Level among Postmenopausal Women with Osteoporosis or Osteopenia: A Randomized Controlled Trial

You-Bin Lee,Ki-Hyun Baek,Ho Yeon Chung,변동원,Yong-Ki Min 대한골대사학회 2022 대한골대사학회지 Vol.29 No.3

Background: We compared the efficacy of a fixed dose combination of raloxifene 60 mg/vitamin D 800 IU to raloxifene 60 mg alone on vitamin D status, as indicated by change in serum 25-hydroxy-vitamin D (25[OH]D) levels. Methods: In this 16-week, open-label, randomized, active controlled, multicenter clinical trial conducted in 4 uni- versity-affiliated hospitals in Korea, postmenopausal women aged 55 to 70 years with osteoporosis or osteopenia were randomly assigned in a 1:1 ratio to receive raloxifene 60 mg/cholecalciferol 800 IU combination therapy or raloxifene 60 mg monotherapy. Primary endpoint was change in serum 25(OH)D level from baseline to 16 weeks after the intervention. Results: A total of 96 participants were randomly assigned to raloxi- fene/vitamin D combination therapy (N= 49) and raloxifene monotherapy (N= 47) groups. At week 16, serum 25(OH)D level increased from baseline, only in the raloxifene/ vitamin D combination therapy group. Change in serum 25(OH)D level from baseline to week 16 was higher in the raloxifene/vitamin D combination therapy group (2.7±6.5 ng/mL) than in the raloxifene monotherapy (-1.7±6.2 ng/mL; P = 0.0034) group. Propor- tions and number of adverse events (AEs) categorized by the System-Organ Class were not different between the groups. There was only one severe AE case (spondylolisthesis; raloxifene/vitamin D group), unlikely to be related to trial intervention. Conclusions: Among postmenopausal women with osteoporosis or osteopenia, a fixed dose combi- nation of raloxifene 60 mg/vitamin D 800 IU showed superior efficacy in elevating serum 25(OH)D levels compared with raloxifene 60 mg alone during 16 weeks of follow-up. The safety of raloxifene/vitamin D combination was comparable to raloxifene alone.

The Beneficial and Adverse Effects of Raloxifene in Menopausal Women: A Mini Review

Imaneh Khorsand,Reyhaneh Kashef,Masumeh Ghazanfarpour,Elaheh Mansouri,Sareh Dashti,Talat Khadivzadeh 대한폐경학회 2018 대한폐경학회지 Vol.24 No.3

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.

A Nationwide Study on the Incidence of Breast Cancer in Korean Women with Osteoporosis Receiving Raloxifene Treatment

이지현,이지성,이종은,김지선,한선욱,허성모,최영진,박성민 한국유방암학회 2021 Journal of breast cancer Vol.24 No.3

Purpose: Raloxifene is a selective estrogen receptor modulator (SERM), and raloxifene treatment for osteoporosis is reimbursable under the Korean National Health Insurance. Evidence suggests that SERMs use reduces the risk of breast cancer in Asian population. Herein, we retrospectively investigated the protective effect of raloxifene on breast cancer rates in Korean population. Methods: Using the Health Insurance Review and Assessment Service database, we selected women with osteoporosis aged 50 years and above. Patients treated for at least 2 years with raloxifene were assigned to the user group, whereas the remaining patients were assigned to the non-user group. The effect on breast cancer risk was assessed using the Cox proportional-hazards model with a time-dependent covariate to adjust for immortal time bias. Results: A total of 322,870 women who were registered between 2010 and 2011 were included. The user group comprised 0.7% (n = 2,307) of the total population. The mean age was 65.7 ± 8.0 years and 67.2 ± 8.6 years in the user and non-user groups, respectively (p < 0.001). There was no difference in the previous use of estrogen replacement between the 2 groups (p = 0.087). The incidence of breast cancer per 1,000 person-years was 0.49 (n = 8) and 0.68 (n = 1,714) in the user and non-user groups, respectively (hazard ratio [HR], 0.63, 95% confidence interval [CI], 0.32–1.27). HR decreased with increase in the treatment duration, but this change was not statistically significant (HR, 1.00, 95% CI, 0.32–3.11 in 2–3 years; HR, 0.63, 95% CI, 0.20–1.94 in 3–4 years; and HR, 0.41, 95% CI, 0.10–1.65 in 4–5 years). Conclusion: Long-term treatment with raloxifene in women with osteoporosis was not significantly associated with a reduction in breast cancer rates. However, further investigation is required for a conclusive proof.

Optimized and Validated Spectrophotometric Methods for the Determination of Raloxifene in Pharmaceuticals Using Permanganate

Kanakapura Basavaiah,Salmara ganeshbhat Hiriyanna,Kanakapura Basavaiah Vinay,Kalsang Tharpa,Urdigere Rangachar Anil Kumar,Nagaraju Rajedraprasad 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.9

Two simple and sensitive spectrophotometric methods are described for the determination of raloxifene hydrochloride (RLX) in pure form and in tablets. The first method (method A) is based on the formation of a yellowish-brown chromogen peaking at 430 nm when RLX was reacted with permanganate in acetic acid medium. In the second method (method B), RLX was reacted with a measured excess of permanganate in H2SO4 medium followed by the spectrophotometric measurement of the unreacted KMnO4 at 550 nm. Under the optimized experimental conditions, Beer’s law is obeyed in the concentration range 0.6-6.0 and 1.5-15.0 μg mL-1 with molar absorptivity of 7.01 × 104 and 2.8 × 104 L mol-1 cm-1 for method A and method B, respectively. The limits of detection (LOD) and quantification (LOQ) have also been reported. The intra-day and inter-day RSD and RE values at three different concentrations were assessed. The proposed methods were applied to the commercially available tablets, and the results were statistically compared with those of the reference method. The accuracy and reliability of the methods were further ascertained by recovery studies.

Raloxifene Administration in Women Treated with Long Term Gonadotropin-releasing Hormone Agonist for Severe Endometriosis: Effects on Bone Mineral Density

( Young Hwa Cho ),( Mi Jung Um ),( Suk Jin Kim ),( Soo Ah Kim ),( Hyuk Jung ) 대한폐경학회 2016 대한폐경학회지 Vol.22 No.3

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. (J Menopausal Med 2016;22:174-179)

The Efficacy of Selective Estrogen Receptor Modulators Monotherapies in Postmenopausal Women with Osteopenia

Kyung Wook Kim,Young-Il Kim,Ki-Choul Kim 대한골대사학회 2022 대한골대사학회지 Vol.29 No.3

Background: The impact of osteopenia as a risk factor for fractures is underrecognized. Moreover, the efficacy of selective estrogen receptor modulators (SERMs) in postmeno- pausal women with osteopenia is limited. This study aimed to evaluate the efficacy of SERMs in postmenopausal women with osteopenia. Methods: Thirty-two postmeno- pausal women with osteopenia were treated with 3 types of SERMs medication: raloxi- fene (group I, N = 15), bazedoxifene (group II, N = 8), and raloxifene with cholecalciferol (group III, N= 9). Bone mineral density (BMD) was measured using dual energy X-ray ab- sorptiometry scans before treatment to after 3 years of treatment once a year. Results: Patients in group I showed significant increases in hip BMD, -1.93 to -1.73 and spine BMD, -1.85 to -1.67. In addition, patients in groups II and III showed significant increases in hip BMD, -1.93 to -1.69 and -2.22 to -1.86, respectively and spine BMD, -2.1 to -1.3 and -2.22 to -1.37, respectively. The BMD increased in the hip and spine by 9.7% and 10.3%, respectively in group I, 38.0% and 12.4%, respectively in group II, and 38.2% and 16.2%, respectively in group III. Conclusions: In this study, we found that SERMs could improve spine and hip BMD. In conclusion, preemptive treatment using SERMs is necessary for postmenopausal women with osteopenia. None of the patients experienced fractures during the follow-up period.

Cost-effectiveness of Pharmaceutical Interventions to Prevent Osteoporotic Fractures in Postmenopausal Women with Osteopenia

권진원,박혜영,김예지,문성환,강혜영 대한골대사학회 2016 대한골대사학회지 Vol.23 No.2

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.