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Toshio Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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Chapter 93 – Eldecalcitol and Osteoporosis
Vitamin D, 2020Co-Authors: Toshio Matsumoto, Fumiaki TakahashiAbstract:Abstract Eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropyloxy)vitamin D3] is an analog of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], bearing a hydroxypropyloxy residue at the 2β position. Its chemical structure gives eldecalcitol unique features of actions with long serum half-life, lower affinity but stable binding to vitamin D receptor, and little metabolism via 24-hydroxylation. Eldecalcitol suppresses bone resorption to a greater extent than Alfacalcidol by reducing osteoclast number but has a similar effect on bone formation because of resorption-independent minimodeling, resulting in a greater increase in bone mineral density in ovariectomized rats. In osteoporotic patients, eldecalcitol shows stronger effects than Alfacalcidol in increasing bone mineral density and reducing bone resorption markers. Once-daily 0.75 μg eldecalcitol reduces the incidence of vertebral fracture compared with 1.0 μg Alfacalcidol. In addition, eldecalcitol strongly reduces wrist fracture incidence. It is not known whether eldecalcitol has a stronger effect in preventing falls than Alfacalcidol.
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eldecalcitol is superior to Alfacalcidol in maintaining bone mineral density in glucocorticoid induced osteoporosis patients e gloria
Journal of Bone and Mineral Metabolism, 2020Co-Authors: Toshio Matsumoto, Tetsuo Nakano, Akihiro Hirakawa, Yoshiya Tanaka, Sakae Tanaka, Tatsuya Tomomitsu, Tsutomu Takeuchi, Kazuhiko Yamamoto, Satoshi SoenAbstract:Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of Alfacalcidol in GIO patients. A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 μg eldecalcitol compared with 1.0 μg Alfacalcidol in GIO patients. Lumbar spine BMD increased with eldecalcitol, but decreased with Alfacalcidol at 12 and 24 months (between group difference 1.29%, p 70% of the young adult mean, and with ≤ 3 months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups. Eldecalcitol was more effective than Alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO. UMIN000011700.
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Eldecalcitol is superior to Alfacalcidol in maintaining bone mineral density in glucocorticoid-induced osteoporosis patients (e-GLORIA)
Journal of Bone and Mineral Metabolism, 2020Co-Authors: Toshio Matsumoto, Tetsuo Nakano, Akihiro Hirakawa, Yoshiya Tanaka, Sakae Tanaka, Tatsuya Tomomitsu, Tsutomu Takeuchi, Kazuhiko Yamamoto, Satoshi SoenAbstract:Introduction Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of Alfacalcidol in GIO patients. Materials and methods A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 μg eldecalcitol compared with 1.0 μg Alfacalcidol in GIO patients. Results Lumbar spine BMD increased with eldecalcitol, but decreased with Alfacalcidol at 12 and 24 months (between group difference 1.29%, p
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eldecalcitol increases bone mineral density in chinese osteoporotic patients without vitamin d or calcium supplementation
Journal of Bone and Mineral Metabolism, 2019Co-Authors: Yan Jiang, Qun Cheng, Hai Tang, Zhenlin Zhang, Tsuyoshi Kobayashi, Satomi Uehara, Shuli He, Wei Yu, Toshio MatsumotoAbstract:: Eldecalcitol increased bone mineral density (BMD) and prevented vertebral fractures in vitamin D-sufficient osteoporotic subjects. However, the effect of eldecalcitol on BMD under vitamin D insufficiency is unknown. We examined the effect of eldecalcitol on BMD compared with Alfacalcidol in osteoporotic patients without vitamin D or calcium supplementation. This is a randomized, double-blind, active comparator trial. 265 Chinese osteoporotic patients were randomly assigned to receive 0.75 μg eldecalcitol or 1.0 μg Alfacalcidol for 12 months without vitamin D or calcium supplementation. Baseline calcium intakes were less than 550 mg/day and mean serum 25-hydroxyvitamin D [25(OH)D] was below 43 nmol/L in both groups. Baseline BMD tended to be lower in patients with lower calcium intake and serum 25(OH)D. Lumbar BMD increased by 2.05% higher in eldecalcitol than Alfacalcidol group at 12 months. Total hip and femoral neck BMD also increased by 1.33 and 1.78%, respectively, in the eldecalcitol than the Alfacalcidol group. The effect of eldecalcitol on BMD was not affected by serum 25(OH)D or calcium intake. The incidence of adverse events was not different between the two groups. Incidence of hypercalcemia in the edecalcitol group was not affected by serum 25(OH)D. In conclusion, baseline BMD tended to be lower in patients with low calcium intake and serum 25(OH)D. Eldecalcitol increased lumbar and hip BMD more than Alfacalcidol regardless of serum 25(OH)D or calcium intake without vitamin D or calcium supplementation. These results suggest that eldecalcitol is effective in increasing the BMD of osteoporotic patients regardless of vitamin D status or calcium intake.Clinical Trial Registration number JAPIC CTI 152904.
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chapter 93 eldecalcitol and osteoporosis
Vitamin D (Fourth Edition)#R##N#Volume 2: Health Disease and Therapeutics, 2018Co-Authors: Toshio Matsumoto, Fumiaki TakahashiAbstract:Abstract Eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropyloxy)vitamin D3] is an analog of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], bearing a hydroxypropyloxy residue at the 2β position. Its chemical structure gives eldecalcitol unique features of actions with long serum half-life, lower affinity but stable binding to vitamin D receptor, and little metabolism via 24-hydroxylation. Eldecalcitol suppresses bone resorption to a greater extent than Alfacalcidol by reducing osteoclast number but has a similar effect on bone formation because of resorption-independent minimodeling, resulting in a greater increase in bone mineral density in ovariectomized rats. In osteoporotic patients, eldecalcitol shows stronger effects than Alfacalcidol in increasing bone mineral density and reducing bone resorption markers. Once-daily 0.75 μg eldecalcitol reduces the incidence of vertebral fracture compared with 1.0 μg Alfacalcidol. In addition, eldecalcitol strongly reduces wrist fracture incidence. It is not known whether eldecalcitol has a stronger effect in preventing falls than Alfacalcidol.
Masataka Shiraki - One of the best experts on this subject based on the ideXlab platform.
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Eldecalcitol is more effective for the prevention of osteoporotic fractures than Alfacalcidol
Journal of Bone and Mineral Metabolism, 2013Co-Authors: Toshitaka Nakamura, Masao Fukunaga, Toshiyuki Takano, Masataka Shiraki, Toshio MatsumotoAbstract:Eldecalcitol, a vitamin D_3 analogue, significantly reduces the risk of new vertebral fractures and increases bone mineral density (BMD) more than does Alfacalcidol. To determine the effect of eldecalcitol on the incidence of all fragility fractures caused by osteoporosis, we conducted post hoc analyses of the phase III clinical trial to evaluate the incidence of the osteoporotic fractures defined in the World Health Organization (WHO) Technical Report, and, also, the incidence of the major osteoporotic fractures utilized in the WHO Fracture Risk Assessment Tool (FRAX), and compared those in the eldecalcitol group with those in the Alfacalcidol group. We also analyzed the incidence of osteoporotic fractures stratified by prespecified risk factors for fractures. Eldecalcitol treatment reduced the incidence of osteoporotic fractures defined by the WHO more than Alfacalcidol treatment (18.6 % vs. 25.2 %; hazard ratio, 0.70; 95 % CI, 0.54–0.93). Prevalent vertebral fractures, two or more prevalent vertebral fractures, and total hip BMD T score less than −2.5 were the risk factors for new osteoporotic fractures with significant differences between the two treatments. Eldecalcitol also decreased the incidence of major osteoporotic fractures in the FRAX more than Alfacalcidol (11.1 % vs. 16.3 %; hazard ratio, 0.66; 95 % CI, 0.46–0.94). In conclusion, treatment with eldecalcitol reduced the risk of fragility fractures caused by osteoporosis compared with Alfacalcidol administration, which may result from a potent effect of eldecalcitol on BMD, bone structure, and bone turnover.
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Eldecalcitol reduces the risk of severe vertebral fractures and improves the health-related quality of life in patients with osteoporosis
Journal of Bone and Mineral Metabolism, 2013Co-Authors: Hiroshi Hagino, Masao Fukunaga, Toshiyuki Takano, Toshitaka Nakamura, Masataka Shiraki, Toshio MatsumotoAbstract:Eldecalcitol reduces the risk of vertebral fractures in comparison to Alfacalcidol in osteoporotic patients under vitamin D repletion. The aim of this study was to evaluate the effects of eldecalcitol on the spinal location of incident vertebral fractures, the severity of the fractures, and the changes in health-related quality of life (HRQOL) compared with those of Alfacalcidol. The post hoc analysis has been performed on the data from the three-year, double-blind, randomized, head-to-head clinical trial of eldecalcitol versus Alfacalcidol conducted in Japan. A total of 1054 patients were enrolled and randomized to take 0.75 μg eldecalcitol or 1.0 μg Alfacalcidol daily for 3 years. The incidence of vertebral fractures was re-evaluated based on the location on the spine (upper T4–T10; lower T11–L4). The severity of vertebral fractures was determined by the semi-quantitative method, and the change in HRQOL was analyzed by using the Medical Outcomes Study Short Form 36-item questionnaire. The incidence of vertebral fracture at the lower spine was less in the eldecalcitol group than in the Alfacalcidol group ( p = 0.029). The incidence of severe vertebral fracture (Grade 3) was 3.8 % in the eldecalcitol group and 6.7 % in the Alfacalcidol group, demonstrated a significant difference between the 2 groups ( p = 0.036). Both eldecalcitol and Alfacalcidol improved HRQOL in osteoporotic patients. Although no significant differences in each HRQOL scores were observed between eldecalcitol and Alfacalcidol during the observational period, overall improvement from baseline of HRQOL scores were clearly observed in the eldecalcitol group. In conclusion, the incidences of lower spinal vertebral fractures and severe vertebral fractures were reduced further by eldecalcitol compared to Alfacalcidol in the 3-year clinical trial. Daily treatment with eldecalcitol is effective in improving HRQOL, possibly owing to the reduced risk of lower spinal vertebral fractures and/or severe vertebral fractures.
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a new active vitamin d3 analog eldecalcitol prevents the risk of osteoporotic fractures a randomized active comparator double blind study
Bone, 2011Co-Authors: Toshio Matsumoto, Yasufumi Hayashi, Takako Hirota, Teruki Sone, Masao Fukunaga, Yusuke Tanigawara, Masataka Shiraki, Toshitaka NakamuraAbstract:Abstract Background Eldecalcitol is an analog of 1,25-dihydroxyvitamin D 3 that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to Alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456. Methods and results This 3 year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75 μg eldecalcitol versus 1.0 μg Alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92 years old were randomly assigned 1:1 to receive eldecalcitol (n = 528) or Alfacalcidol (n = 526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels ( 3 . Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the Alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36 months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56–0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than Alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11–0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups. Conclusions Eldecalcitol is more efficacious than Alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to Alfacalcidol.
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Alfacalcidol reduces accelerated bone turnover in elderly women with osteoporosis
Journal of Bone and Mineral Metabolism, 2004Co-Authors: Masataka Shiraki, Masayuki Fukuchi, Takeshi Kiriyama, Sumiaki Okamoto, Takehisa Ueno, Hiroshi Sakamoto, Tsuneji NagaiAbstract:To evaluate the effects of Alfacalcidol on bone turnover in elderly women with osteoporosis, an open-label, prospective, calcium-controlled study was conducted. A total of 80 patients with osteoporosis were divided into two groups: the control group, group C (mean age, 78.0 years), in which patients were given calcium, and group D (mean age, 77.4 years), in which the patients were given Alfacalcidol 1 µg/day together with calcium for 6 months. Calcium regulation, lumbar bone mineral density (LBMD), and markers for bone turnover were assessed. A significant increase in urinary calcium/creatinine ratio (90% increase from baseline at 3 months; P = 0.0083, and 60% at 6 months; P = 0.0091) and a significant decrease in serum parathyroid hormone (30% decrease from baseline at 6 months; P < 0.0001) was observed in group D compared with the corresponding changes in group C. Significant decreases of bone resorption markers (deoxypyridinoline and N-telopeptide) at 6 months (about 15% decrease from the baseline values) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers (bone-derived alkaline phosphatase and osteocalcin) in group D were significantly different at 6 months (−21.5%; P = 0.0047 and −13.4%; P = 0.0032, respectively) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values, suggesting that Alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates. The LBMD in group D increased by 1.7% and that in group C decreased by 1.6% (P = 0.0384). The changes in calcium metabolism and LBMD were in good agreement with those in previous reports. Although the changes in bone turnover markers in group D were slight, significant reduction in bone turnover with Alfacalcidol treatment, together with the change in calcium metabolism, may account for the effects of Alfacalcidol on BMD and on fracture prevention reported previously. In conclusion, Alfacalcidol reduces bone turnover in elderly women with high-bone-turnover osteoporosis, and it may have beneficial effects on bone.
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A Double-Masked Multicenter Comparative Study Between Alendronate and Alfacalcidol in Japanese Patients with Osteoporosis
Osteoporosis International, 1999Co-Authors: Masataka Shiraki, Masao Fukunaga, Kazuhiro Kushida, Hideaki Kishimoto, Michiyoshi Taga, T Nakamura, Kiyoshi Kaneda, Hiroshi Minaguchi, T Inoue, H MoriiAbstract:To evaluate the efficacy and safety of alendronate, a double-masked, active (Alfacalcidol) controlled comparative study for 48 weeks was carried out in a total of 210 Japanese patients with osteoporosis. The doses of alendronate and Alfacalcidol were 5 mg/day and 1 μg/day, respectively. The lumbar bone mineral density (LBMD) values observed at 12, 24, 36 and 48 weeks after the initiation of alendronate treatment were 3.53 ± 0.53%, 5.37 ± 0.62%, 5.87 ± 0.74% and 6.21 ± 0.59% (mean ± SE), respectively, higher than the baseline value. Corresponding values in the Alfacalcidol group were 1.50 ± 0.43%, 0.69 ± 0.63%, 1.12 ± 0.60% and 1.36 ± 0.63%, respectively. There was a significant difference between the two groups at each time point (p
Michio Sata - One of the best experts on this subject based on the ideXlab platform.
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clinical trial comparison of alendronate and Alfacalcidol in glucocorticoid associated osteoporosis in patients with ulcerative colitis
Alimentary Pharmacology & Therapeutics, 2009Co-Authors: S Kitazaki, Keiichi Mitsuyama, J Masuda, Kazunori Harada, Hiroshi Yamasaki, Kotaro Kuwaki, Hidetoshi Takedatsu, Gen Sugiyama, Osamu Tsuruta, Michio SataAbstract:Summary Background Bone loss is often observed in patients with ulcerative colitis, particularly if they require glucocorticoids. Aim To determine whether the bisphosphonate, alendronate, is safe and effective in preserving bone mass compared to the active vitamin D3, Alfacalcidol, in ulcerative colitis patients receiving glucocorticoids. Methods Thirty-nine patients with ulcerative colitis and treated with glucocorticoids were randomized to receive alendronate (5 mg/day) or Alfacalcidol (1 μg/day) daily for 12 months. Loss of bone mass was evaluated by bone mineral density, bone resorption by urinary N-telopeptide for type I collagen, and bone formation by serum bone alkaline phosphatase. Results Alendronate, but not Alfacalcidol, significantly increased bone mineral density in the lumbar spine. Alendronate decreased serum bone alkaline phosphatase levels, but Alfacalcidol did not. Urinary N-telopeptide for type I collagen levels decreased in both groups, but were significantly lower in the alendronate group. There were no significant differences in the adverse events in the two groups. Conclusion Our study indicates that alendronate is a safe, well-tolerated and more effective therapy than Alfacalcidol for preventing glucocorticoid-associated bone loss in patients with ulcerative colitis.
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Clinical trial: comparison of alendronate and Alfacalcidol in glucocorticoid‐associated osteoporosis in patients with ulcerative colitis
Alimentary Pharmacology & Therapeutics, 2008Co-Authors: S Kitazaki, Keiichi Mitsuyama, J Masuda, Kazunori Harada, Hiroshi Yamasaki, Kotaro Kuwaki, Hidetoshi Takedatsu, Osamu Tsuruta, Sugiyama, Michio SataAbstract:Summary Background Bone loss is often observed in patients with ulcerative colitis, particularly if they require glucocorticoids. Aim To determine whether the bisphosphonate, alendronate, is safe and effective in preserving bone mass compared to the active vitamin D3, Alfacalcidol, in ulcerative colitis patients receiving glucocorticoids. Methods Thirty-nine patients with ulcerative colitis and treated with glucocorticoids were randomized to receive alendronate (5 mg/day) or Alfacalcidol (1 μg/day) daily for 12 months. Loss of bone mass was evaluated by bone mineral density, bone resorption by urinary N-telopeptide for type I collagen, and bone formation by serum bone alkaline phosphatase. Results Alendronate, but not Alfacalcidol, significantly increased bone mineral density in the lumbar spine. Alendronate decreased serum bone alkaline phosphatase levels, but Alfacalcidol did not. Urinary N-telopeptide for type I collagen levels decreased in both groups, but were significantly lower in the alendronate group. There were no significant differences in the adverse events in the two groups. Conclusion Our study indicates that alendronate is a safe, well-tolerated and more effective therapy than Alfacalcidol for preventing glucocorticoid-associated bone loss in patients with ulcerative colitis.
Toshitaka Nakamura - One of the best experts on this subject based on the ideXlab platform.
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Eldecalcitol is more effective for the prevention of osteoporotic fractures than Alfacalcidol
Journal of Bone and Mineral Metabolism, 2013Co-Authors: Toshitaka Nakamura, Masao Fukunaga, Toshiyuki Takano, Masataka Shiraki, Toshio MatsumotoAbstract:Eldecalcitol, a vitamin D_3 analogue, significantly reduces the risk of new vertebral fractures and increases bone mineral density (BMD) more than does Alfacalcidol. To determine the effect of eldecalcitol on the incidence of all fragility fractures caused by osteoporosis, we conducted post hoc analyses of the phase III clinical trial to evaluate the incidence of the osteoporotic fractures defined in the World Health Organization (WHO) Technical Report, and, also, the incidence of the major osteoporotic fractures utilized in the WHO Fracture Risk Assessment Tool (FRAX), and compared those in the eldecalcitol group with those in the Alfacalcidol group. We also analyzed the incidence of osteoporotic fractures stratified by prespecified risk factors for fractures. Eldecalcitol treatment reduced the incidence of osteoporotic fractures defined by the WHO more than Alfacalcidol treatment (18.6 % vs. 25.2 %; hazard ratio, 0.70; 95 % CI, 0.54–0.93). Prevalent vertebral fractures, two or more prevalent vertebral fractures, and total hip BMD T score less than −2.5 were the risk factors for new osteoporotic fractures with significant differences between the two treatments. Eldecalcitol also decreased the incidence of major osteoporotic fractures in the FRAX more than Alfacalcidol (11.1 % vs. 16.3 %; hazard ratio, 0.66; 95 % CI, 0.46–0.94). In conclusion, treatment with eldecalcitol reduced the risk of fragility fractures caused by osteoporosis compared with Alfacalcidol administration, which may result from a potent effect of eldecalcitol on BMD, bone structure, and bone turnover.
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Eldecalcitol reduces the risk of severe vertebral fractures and improves the health-related quality of life in patients with osteoporosis
Journal of Bone and Mineral Metabolism, 2013Co-Authors: Hiroshi Hagino, Masao Fukunaga, Toshiyuki Takano, Toshitaka Nakamura, Masataka Shiraki, Toshio MatsumotoAbstract:Eldecalcitol reduces the risk of vertebral fractures in comparison to Alfacalcidol in osteoporotic patients under vitamin D repletion. The aim of this study was to evaluate the effects of eldecalcitol on the spinal location of incident vertebral fractures, the severity of the fractures, and the changes in health-related quality of life (HRQOL) compared with those of Alfacalcidol. The post hoc analysis has been performed on the data from the three-year, double-blind, randomized, head-to-head clinical trial of eldecalcitol versus Alfacalcidol conducted in Japan. A total of 1054 patients were enrolled and randomized to take 0.75 μg eldecalcitol or 1.0 μg Alfacalcidol daily for 3 years. The incidence of vertebral fractures was re-evaluated based on the location on the spine (upper T4–T10; lower T11–L4). The severity of vertebral fractures was determined by the semi-quantitative method, and the change in HRQOL was analyzed by using the Medical Outcomes Study Short Form 36-item questionnaire. The incidence of vertebral fracture at the lower spine was less in the eldecalcitol group than in the Alfacalcidol group ( p = 0.029). The incidence of severe vertebral fracture (Grade 3) was 3.8 % in the eldecalcitol group and 6.7 % in the Alfacalcidol group, demonstrated a significant difference between the 2 groups ( p = 0.036). Both eldecalcitol and Alfacalcidol improved HRQOL in osteoporotic patients. Although no significant differences in each HRQOL scores were observed between eldecalcitol and Alfacalcidol during the observational period, overall improvement from baseline of HRQOL scores were clearly observed in the eldecalcitol group. In conclusion, the incidences of lower spinal vertebral fractures and severe vertebral fractures were reduced further by eldecalcitol compared to Alfacalcidol in the 3-year clinical trial. Daily treatment with eldecalcitol is effective in improving HRQOL, possibly owing to the reduced risk of lower spinal vertebral fractures and/or severe vertebral fractures.
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a new active vitamin d3 analog eldecalcitol prevents the risk of osteoporotic fractures a randomized active comparator double blind study
Bone, 2011Co-Authors: Toshio Matsumoto, Yasufumi Hayashi, Takako Hirota, Teruki Sone, Masao Fukunaga, Yusuke Tanigawara, Masataka Shiraki, Toshitaka NakamuraAbstract:Abstract Background Eldecalcitol is an analog of 1,25-dihydroxyvitamin D 3 that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to Alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456. Methods and results This 3 year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75 μg eldecalcitol versus 1.0 μg Alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92 years old were randomly assigned 1:1 to receive eldecalcitol (n = 528) or Alfacalcidol (n = 526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels ( 3 . Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the Alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36 months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56–0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than Alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11–0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups. Conclusions Eldecalcitol is more efficacious than Alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to Alfacalcidol.
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Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis distinct actions from estrogen
Journal of Bone and Mineral Research, 2010Co-Authors: Ayako Shiraishi, Noboru Kubodera, Toshitaka Nakamura, Satoshi Takeda, Toshimi Masaki, Yoshinobu Higuchi, Yasushi Uchiyama, K Sato, M Kyoji D Ikeda, Toshio MatsumotoAbstract:Although Alfacalcidol has been widely used for the treatment of osteoporosis in certain countries, its mechanism of action in bone, especially in the vitamin D–replete state, remains unclear. Here we provide histomorphometric as well as biochemical evidence that Alfacalcidol suppresses osteoclastic bone resorption in an ovariectomized rat model of osteoporosis. Furthermore, when compared with 17β-estradiol, a representative antiresorptive drug, it is evident that Alfacalcidol causes a dose-dependent suppression of bone resorption, and yet maintains or even stimulates bone formation, as reflected in increases in serum osteocalcin levels and bone formation rate at both trabecular and cortical sites. 17β-Estradiol, which suppresses bone resorption to the same extent as Alfacalcidol, causes a parallel reduction in the biochemical and histomorphometric markers of bone formation. As a final outcome, treatment with Alfacalcidol increases bone mineral density and improves mechanical strength more effectively than 17β-estradiol, with a more pronounced difference in cortical bone. We conclude that estrogens depress bone turnover primarily by suppressing bone resorption and, as a consequence, bone formation as well, whereas Alfacalcidol “supercouples” these processes, in that it suppresses bone resorption while maintaining or stimulating bone formation.
Jelena Vojinovic - One of the best experts on this subject based on the ideXlab platform.
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ab0079 Alfacalcidol suplementation modulates cytokine production in peripheral blood mononuclear cells culture of patients with active rheumatoid arthritis
Annals of the Rheumatic Diseases, 2018Co-Authors: Zivanovic T Radnic, Nemanja Damjanov, Simic K Pasalic, Sefik M Bukilica, Jelena VojinovicAbstract:Background Hormone D and its analogues display immunomodulatory activities that provide a beneficial effect in immunoinflammatory diseases. However, whether this hormone has an additive immunosuppressive effect when it is used with corticosteroids has not been investigated, although these agents are commonly used together. Objectives Testing the immunomodulatory in vitro effects of vitamin D analogue, Alfacalcidol, in peripheral blood mononuclear cells (PBMC) cultures of patients with active rheumatoid arthritis (RA). Methods Sixteen patients with active RA were enrolled in the study. Patients PBMCs were isolated, stimulated with PMA/Ionomycin and cultivated for 48 hours at 37°C, 5% CO2 in cell cultures medium with or without supplementation. In vitro effects of supplementation with Alfacalcidol (concentration 10 nM), calcitriol (concentration 10 nM), methylprednisolone (concentration 400 nM) and cotreatment with Alfacalcidol/methylprednisolone on cytokine production were studied. Stimulated production of cytokines IL-6, IL-17, IL-21, TNF-α, IL-4, IL-10, TGF-β and IFN-γ were determined in cell culture supernatant by standard ELISA method. Results In vitro Alfacalcidol supplementation reduces the production of proinflammatory cytokines IL-17 (p=0.001), IL-21 (p=0.001), TNF-α (p=0.002) and IL-6 (p=0.4), and induce more intense anti-inflammatory cytokine production IL-4 (p Conclusions Alfacalcidol, in vitro, showed a significant immunomodulatory effect through the specific inhibition of Th1- cytokine production, while Th2 cell response was enhanced – “Th2 switch”. Our results demonstrate that Alfacalcidol has significant additive effects on glycocorticoid-mediated inhibition of Th1 cytokine production when combined with methylprednisolone. These findings demonstrate the potential use of Alfacalcidol as an immunosuppressive agent when combined with corticosteroids in Th1, but not Th2, immune response. References [1] Živanovic Radnic T, Simic-Pasalic K, Sefik Bukilica M, Misirlic Dencic S, Isakovic AM, Stojkovic T, Petronijevic N, Damjanov N, Vojinovic J. J. Serb. Chem. Soc2016. doi:10.2298/JSC160506039Z [2] Cutolo M. Vitamin D and autoimmune rheumatic diseases. Rheumatology2008. [3] Andjelkovic Z, Vojinovic J, Pejnovic N, Popovic M, Dujic A, Mitrovic D, et al. Disease modifynig and immunoregulatory effects of high oral dose 1a(OH)D3 in rheumatoid arthritis patients. Clin Exp Rheumatol1999;17(4):59–62. Disclosure of Interest None declared
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Alfacalcidol modulates oxidative stress parameters in the peripheral blood of patients with active rheumatoid arthritis
Journal of The Serbian Chemical Society, 2016Co-Authors: Tatjana Zivanovicradnic, Katarina Simicpasalic, M Sefikbukilica, Sonja Misirlicdencic, Andjelka M Isakovic, Tihomir Stojkovic, Natasa Petronijevic, Nemanja Damjanov, Jelena VojinovicAbstract:Hormone D and its analogues display immunomodulatory activities providing a beneficial effect in immunoinflammatory diseases. The aim of this study was to assess the effect of Alfacalcidol treatment on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity and glutathione (GSH) and malondialdehyde (MDA) levels in patients with active RA. Sixteen patients with active RA and twenty controls were enrolled in the study. Blood samples were taken before and after 12 weeks of Alfacalcidol therapy (2 μg/day). Oxidative stress parameters were determined spectrophotometrically and by flow cytometry assessment. Disease activity was assessed using DAS28 score. The results revealed that Alfacalcidol treatment, significantly ( p = 0.04) reduced SOD activity and CAT activity ( p = 0.001) in RA patients. The activity of GPx was significantly lower in RA patients before treatment, compared to controls ( p = 0.04). After therapy, GPx activity was restored to control levels, and GSH levels were significantly reduced ( p = 0.01). MDA levels in patients at the beginning of the study protocol, remained significantly elevated compared to controls ( p = 0.01). Alfacalcidol treatment decreased MDA levels in patients ( p = 0.19). Furthermore, 12-weeks Alfacalcidol therapy, changed the response of RA patients’ PBMC to stimulation preventing the O 2 - production and mitochondrial membrane depolarisation. After Alfacalcidol treatment, significant clinical improvement was observed.
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sat0228 high doses of Alfacalcidol or prednisone combined with basic therapy are there some more advantages for patients with active rheumatoid arthritis
Annals of the Rheumatic Diseases, 2015Co-Authors: Simic K Pasalic, Nemanja Damjanov, Zivanovic T Radnic, Sefik M Bukilica, A Andjelkovic, Jelena VojinovicAbstract:Background The discovery of vitamin D receptor (VDR) in immune cells and the fact that some of these cells produce D hormone, indicated its antiinflammatory and immunoregulatory properties. Alfacalcidol is a VDR agonist. Objectives To investigate the clinical effect of adding high doses of Alfacalcidol or prednisone in patients with active rheumatoid arthritis (RA), to standard basic therapy Methods The study which was approved by the Ethics Committee and the Drugs Agency and included active RA patients from the Rheumatology Institute in Belgrade, on standard prior methotrexate (MTX) use, for more than 3 months. After signing a consent for participation, demographic and clinical data were collected, disease activity (DAS 28), functional status (HAQ questionnaire), muscle function (timed up and go test -TUG and six minutes walk test- 6MWT) and quality of life (SF36 questionnaire) were assessed. Patients were randomly assigned to receive three-months treatment of 1 μg, 2μg, 3μg Alfacalcidol or prednisone 20mg orally daily, with background MTX. They were monthly followed for clinical and laboratory findings, as well as adverse events (AE). At the end of treatment period, all tests were repeated and compared with the baseline ones. Statistical analysis was performed using the SPSS package. Results Out of 67 pts, who were comparable, 39 were females, average age 56,36 years, disease duration 7,65 years, DAS28 5,6, HAQ 0,58, MTX dose 15,48mg/weekly, serum 25(OH)D3 level 31.5 ng/ml. After 12 weeks of treatment, all four treatment arms significantly reduced DAS 28 (5,6 vs 4,4), HAQ (0,58 vs 0,4), improved PSC QoL (36,39 vs 38,9), 6MWT (404,5 vs 464 m) ( p =0,01, 0,03 and 0,001 respectively), while patients receiving Alfacalcidol (N=51) also improved TUG (7,26 vs 6,69s), MCS QoL (48,1 vs 50,57), serum levels of HDL cholesterol (1,5 vs 1,62 mmol/l, p =0,006). Serum levels of 25(OH)D3 in prednisone users (N=16) significantly decreased (37,02 vs 21,93 ng/ml, p =0,000). Multiple comparison showed that Alfacalcidol 2mg treated pts (N=19) improved DAS28, HAQ, PCS and MCS QoL significantly better than others ( p p =0,001). Conclusions Three months treatment with high doses of Alfacalcidol in vitamin D replete active RA patients, led to improvement of disease activity, functional status, PCSQoL comparable to prednisone use, but also improved MCSQoL, muscle function and serum levels of HDL cholesterol, while preserving serum levels of 25(OH)D3. Disclosure of Interest None declared
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ab0600 Alfacalcidol d hormone analog modulate inflammatory cytokine production without conversion to calcitriol
Annals of the Rheumatic Diseases, 2013Co-Authors: Jelena Vojinovic, M Sefikbukilica, T Zivanovicradnic, K Simicpasalic, Nemanja DamjanovAbstract:Background D hormone 1,25(OH)2D3 (calcitriol) is believed to be the only active form of D hormone (synthesized from vitamin D - cholecalciferol) within the body. It is well known that high doses of D hormone exert immunomodulatory properties that could benefit rheumatoid arthritis [1]. Alfacalcidol, synthetic D hormone analogue 1(OH)D3, compared to calcitriol, is known for its safer profile (lower hypercalcemic activity) when used in higher doses. Mostly it is used for prophylaxis and treatment of osteoporosis, but some encouraging results were achieved in rheumatoid arthritis as well [2]. Actually it is believed that Alfacalcidol must be hydroxylated at 25 position (conversion to calcitriol) to induce any effect on cells. Objectives Aim of the study was to investigate if Alfacalcidol itself could influence cytokine production, as calcitriol does, shifting Th1 to Th2 profile. Methods Isolated peripheral blood mononuclear cells (PBMC), from 20 healthy volunteers, were stimulated with PMA and Ionomycin and cultivated in cell cultures (48 hours at 37°C, 5% CO 2 ) medium without supplements or supplemented with 10 nM of Alfacalcidol or calcitriol, respectively. Produced levels of IL-17A, IL-21, IL-23, IFN-γ, TNF-α, and IL-4 were measured in cell culture supernatant by standard manufacturer ELISA method. Results In vitro test results have shown that Alfacalcidol can act on cells directly, and there was no statistically significant difference compared to calcitriol. Compared to controls, without any supplements in culture, Alfacalcidol and calcitriol significantly reduced production of IL-17 (p Conclusions This is the first prove that Alfacalcidol, as a synthetic vitamin D analogue, may act on cells directly, without 25-hydroxylation to calcitriol. Same as calcitriol, it has immunomodulatory potential, promoting Th2 while inhibiting Th1-cytokine profile. Better safety profile when used in high doses and ability to suppress Th17 production in activated cells could provide considerable therapeutic potential on lymphocyte differentiation and osteoclasts benefiting RA and secondary osteoporosis. References Cutolo M. Vitamin D and autoimmune rheumatic diseases. Arthritis Research & Therapy 2008; 10:123-4 Andjelkovic Z, Vojinovic J, Pejnovic N et al. Disease modifynig and immunoregulatory effects of high oral dose 1a(OH)D3 in rheumatoid arthritis patients. Clin Exp Rheumatol 1999; 17(4): 59-62. Disclosure of Interest None Declared
