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Efficacy and safety of weekly alendronate plus vitamin D? 5600 IU versus weekly alendronate alone in Korean osteoporotic women: 16-week randomized trial.

ABSTRACT: Vitamin D (vit-D) is essential for bone health, although many osteoporosis patients have low levels of 25-hydroxy-vit-D [25(OH)D]. This randomized, open-label study compared the effects of once weekly alendronate 70 mg containing 5600 IU vit-D? (ALN/D5600) to alendronate 70 mg without additional vit-D (ALN) on the percent of patients with vit-D insufficiency [25(OH)D <15 ng/mL, primary endpoint] and serum parathyroid hormone (PTH, secondary endpoint) levels in postmenopausal, osteoporotic Korean women. Neuromuscular function was also measured. A total of 268 subjects were randomized. Overall, 35% of patients had vit-D insufficiency at baseline. After 16-weeks, there were fewer patients with vit-D insufficiency in the ALN/D5600 group (1.47%) than in the ALN group (41.67%) (p<0.001). Patients receiving ALN/D5600 compared with ALN were at a significantly decreased risk of vit-D insufficiency [odds ratio=0.02, 95% confidence interval (CI) 0.00-0.08]. In the ALN/D5600 group, significant increases in serum 25(OH)D were observed at weeks 8 (9.60 ng/mL) and 16 (11.41 ng/mL), where as a significant decrease was recorded in the ALN group at week 16 (-1.61 ng/mL). By multiple regression analysis, major determinants of increases in serum 25(OH)D were ALN/D5600 administration, seasonal variation, and baseline 25(OH)D. The least squares mean percent change from baseline in serum PTH in the ALN/D5600 group (8.17%) was lower than that in the ALN group (29.98%) (p=0.0091). There was no significant difference between treatment groups in neuromuscular function. Overall safety was similar between groups. In conclusion, the administration of 5600 IU vit-D in the ALN/D5600 group improved vit-D status and reduced the magnitude of PTH increase without significant side-effects after 16 weeks in Korean osteoporotic patients.

SUBMITTER: Kim KJ

PROVIDER: S-EPMC3990072 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Efficacy and safety of weekly alendronate plus vitamin D₃ 5600 IU versus weekly alendronate alone in Korean osteoporotic women: 16-week randomized trial.

Kim Kwang Joon KJ Min Yong-Ki YK Koh Jung-Min JM Chung Yoon-Sok YS Kim Kyoung Min KM Byun Dong-Won DW Kim In Joo IJ Kim Mikyung M Kim Sung-Soo SS Min Kyung Wan KW Han Ki Ok KO Park Hyoung Moo HM Shin Chan Soo CS Choi Sung Hee SH Park Jong Suk JS Chung Dong Jin DJ Mok Ji Oh JO Baek Hong Sun HS Moon Seong-Hwan SH Kim Yong Soo YS Lim Sung-Kil SK

Yonsei medical journal 20140401 3

Vitamin D (vit-D) is essential for bone health, although many osteoporosis patients have low levels of 25-hydroxy-vit-D [25(OH)D]. This randomized, open-label study compared the effects of once weekly alendronate 70 mg containing 5600 IU vit-D₃ (ALN/D5600) to alendronate 70 mg without additional vit-D (ALN) on the percent of patients with vit-D insufficiency [25(OH)D <15 ng/mL, primary endpoint] and serum parathyroid hormone (PTH, secondary endpoint) levels in postmenopausal, osteoporotic Korean ...[more]

PMID: 24719139

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Project description:In this randomized, controlled trial, sequential therapy with once-weekly subcutaneous injection of teriparatide for 72 weeks, followed by alendronate for 48 weeks resulted in a significantly lower incidence of morphometric vertebral fracture than monotherapy with alendronate for 120 weeks in women with osteoporosis at high risk of fracture.PurposeTo determine whether the anti-fracture efficacy of sequential therapy with teriparatide, followed by alendronate is superior to that of monotherapy with alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed.MethodsJapanese women aged at least 75 years were eligible for the study, if they had primary osteoporosis and if they were at high risk of fracture. Patients were randomly assigned (1:1) to receive the sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks, followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint in the final analysis was the incidence of morphometric vertebral fracture during the 120-week follow-up period.ResultsBetween October 2014 and June 2020, 505 patients in the sequential therapy group and 506 in the monotherapy group were enrolled. Of these, 489 and 496, respectively, were included in the main analysis. The incidence of morphometric vertebral fracture during the 120-week follow-up period in the sequential therapy group (64 per 627.5 person-years, annual incidence rate 0.1020) was significantly lower than that in the monotherapy group (126 per 844.2 person-years, annual incidence rate 0.1492), with a rate ratio of 0.69 (95% confidence interval 0.54 to 0.88, P < 0.01). After 72 weeks, no patient had a severe adverse event that was considered related to the study drug.ConclusionOnce-weekly injection of teriparatide, followed by alendronate resulted in a significantly lower incidence of morphometric vertebral fracture than alendronate monotherapy in women with osteoporosis who were at high risk of fracture. TRIAL REGISTRATION NUMBER, DATE OF REGISTRATION: jRCTs031180235 and UMIN000015573, March 12, 2019.

Project description:Using a Markov microsimulation model among hypothetical cohorts of community-dwelling older osteoporotic Japanese women with prior vertebral fracture over a lifetime horizon, we found that daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years was not cost-effective compared with alendronate monotherapy for 10 years.PurposeTeriparatide has proven efficacy in reducing osteoporotic fractures, but with substantial cost. We examined the cost-effectiveness of sequential teriparatide/alendronate (i.e., daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years) compared with alendronate monotherapy for 10 years among community-dwelling older osteoporotic women with prior clinical or morphometric vertebral fracture in Japan.MethodsUsing a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life year [QALY]) from the perspective of a single payer responsible for both public healthcare and long-term care. We assumed a lifetime horizon with a willingness-to-pay of ¥5million (or $47,500) per QALY in the base case. We modeled the cost of biosimilar teriparatide, which has been available since November 2019 in Japan, assuming the efficacy was the same as that of the brand version.ResultsIn the base case, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy. In deterministic sensitivity analyses, sequential teriparatide/alendronate would become cost-effective with 85%, 50%, and 15% price discounts to teriparatide at ages 70, 75, and 80, respectively, compared to the current biosimilar cost. Otherwise, results were especially sensitive to changes that affected efficacy of teriparatide or alendronate. In probabilistic sensitivity analyses, the probabilities of sequential teriparatide/alendronate being cost-effective were 0%, 1%, and 37% at ages 70, 75, and 80, respectively.ConclusionsAmong high-risk osteoporotic women in Japan, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy, even with the availability of biosimilar teriparatide.

Project description:Teriparatide, currently only available in brand form in the United States, is a costly drug approved for the treatment of postmenopausal osteoporotic women who are at high risk of fracture. Because market exclusivity for brand teriparatide expired in August 2019 in the US, we sought to understand the potential health economic impact of the availability of generic or biosimilar (generic/biosimilar) teriparatide. We examined the cost-effectiveness of daily teriparatide for 2?years followed by weekly alendronate for 10?years (ie, sequential teriparatide/alendronate) compared with alendronate alone for 10?years in community-dwelling white osteoporotic women with prior vertebral fracture at ages 65, 70, 75, and 80. Using an updated version of previously validated Markov microsimulation models, we obtained incremental cost-effectiveness ratios (ICERs) (dollars [$] per quality-adjusted life year [QALY]) with a willingness-to-pay (WTP) of $150,000 per QALY from a societal perspective with a lifelong time horizon. In the base case, we estimated the annual cost of teriparatide to be $20,161, based on the assumption of 10% brand usage (at a cost of $27,618) and 90% generic/biosimilar usage (priced 30% lower than brand). The ICERs of sequential teriparatide/alendronate compared with alendronate alone were greater than $280,000 per QALY at all ages examined. In deterministic sensitivity analyses, results were sensitive to teriparatide's cost, with the cost of a generic/biosimilar product needing to be 65% to 85% lower than brand for sequential teriparatide/alendronate to be cost-effective. In probabilistic sensitivity analyses, under the assumption that the annual cost of teriparatide was $20,161, the probabilities of sequential teriparatide/alendronate being cost-effective were less than 4% at a WTP of $150,000 per QALY. In conclusion, among community-dwelling older osteoporotic women with prior vertebral fracture in the US, even with the potential availability of generic/biosimilar teriparatide, sequential teriparatide/alendronate would not be cost-effective unless the cost of generic/biosimilar teriparatide were heavily discounted with respect to the current brand cost. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Project description:Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

Project description:Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years. Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.

Project description:UNLABELLED:The randomised, double blind intervention trial 'Optimising Vitamin D Status in Older People' (VDOP) will test the effect of three oral dosages of vitamin D given for one year on bone mineral density (BMD) and biochemical markers of vitamin D metabolism, bone turnover and safety in older people. VDOP is funded by Arthritis Research UK, supported through Newcastle University and MRC Human Nutrition Research and sponsored by the Newcastle upon Tyne Hospitals NHS Foundation Trust.a BACKGROUND:Vitamin D insufficiency is common in older people and may lead to secondary hyperparathyroidism, bone loss, impairment of muscle function and increased risk of falls and fractures. Vitamin D supplementation trials have yielded conflicting results with regard to decreasing rates of bone loss, falls and fractures and the optimal plasma concentration of 25 hydroxy vitamin D (25OHD) for skeletal health remains unclear. METHOD/DESIGN:Older (?70 years) community dwelling men and women are recruited through General Practices in Northern England and 375 participants are randomised to take 12,000 international units (IU), 24,000 IU or 48,000 IU of vitamin D3 orally each month for one year starting in the winter or early spring. Hip BMD and anthropometry are measured at baseline and 12 months. Fasting blood samples are collected at baseline and three-month intervals for the measurement of plasma 25OHD, parathyroid hormone (PTH), biochemical markers of bone turnover and biochemistry to assess the dose-response and safety of supplementation. Questionnaire data include falls, fractures, quality of life, adverse events and outcomes, compliance, dietary calcium intake and sunshine exposure. DISCUSSION:This is the first integrated vitamin D supplementation trial in older men and women using a range of doses given at monthly intervals to assess BMD, plasma 25OHD, PTH and biochemical markers of bone turnover and safety, quality of life and physical performance. We aim to investigate the vitamin D supplementation and plasma 25OHD concentration required to maintain bone health and to develop a set of biochemical markers that reflects the effect of vitamin D on bone. This will aid future studies investigating the effect of vitamin D supplementation on fracture risk.#ISRCTN 35648481 (assigned 16 August 2012), EudraCT 2011-004890-10.

Project description:This analysis assessed whether responses with exenatide once weekly plus dapagliflozin (n?=?231), exenatide once weekly alone (n?=?230), or dapagliflozin alone (n?=?233) differed in key patient subpopulations of the DURATION-8 trial. Potential treatment-by-subgroup interactions for changes in glycated haemoglobin (HbA1c) and body weight after 28?weeks were evaluated among subgroups determined by baseline HbA1c, age, sex, body mass index, type 2 diabetes duration, race, ethnicity and estimated glomerular filtration rate (eGFR). Exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all subgroups: least-squares mean reductions ranged from -8.4 to -26.1?mmol/mol (-0.77% to -2.39%) for HbA1c and from -2.07 to -4.55?kg for body weight. Potential treatment-by-subgroup interactions (P?<?.10) were found for HbA1c change by age (P?= .016) and eGFR (P?= .097). Age subgroup analysis findings were not consistent with expected mechanistic effects, with the small number of patients aged ?65?years (n?=?74 vs n?=?499 for patients aged <65?years) limiting the interpretability of the interaction term. In the exenatide once weekly plus dapagliflozin and dapagliflozin groups, but not the exenatide once weekly group, HbA1c reductions were greater among patients with eGFR ?90 vs ?60 to <90?mL/min/1.73?m2 (least-squares mean reductions of -23.6 vs -19.0?mmol/mol [-2.16% vs -1.74%], -17.3 vs -12.0?mmol/mol [-1.58% vs -1.10%], and -17.7 vs -16.9?mmol/mol [-1.62% vs -1.55%] for the respective treatments); this was consistent with the mechanism of action of dapagliflozin. A potential treatment-by-subgroup interaction was observed for change in body weight by sex (P?= .099), with greater weight loss for women vs men across all treatments (range?-2.56 to -3.98?kg vs -0.56 to -2.99?kg). In conclusion, treatment with exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all patient subgroups and was more effective than exenatide once weekly or dapagliflozin alone in all adequately sized subgroups.

Project description:BackgroundIt is generally believed that Thai people do not suffer from hypovitaminosis D because there is abundant sunlight throughout the year, and that taking vitamin D supplements could result in abnormally high levels of vitamin D. This is a Thai FDA-driven study to investigate this risk over a period of 26 weeks of taking alendronate sodium/vitamin D3 combination tablets.MethodsOsteoporosis patients in Thailand were recruited to a multicenter, open-label, 6-month trial of oral alendronate sodium 70 mg/vitamin D3 5600 IU. Patients received study medication once a week for 26 weeks. Serum 25-hydroxyvitamin D (25(OH)D) and Beta-CrossLaps (β-CTx) levels were measured at baseline and 26 weeks. The primary endpoint was the proportion of patients with 25(OH)D ≥ 50 ng/mL at week 26; it was hypothesized that 26 weeks' treatment would not result in 25(OH)D serum levels ≥ 50 ng/mL in > 7% of osteoporosis patients.ResultsOne hundred ninety-eight patients were recruited. At baseline, 67.2% of the patients had 25(OH)D < 30 ng/mL; this declined to 34.4% by week 26. The mean 25(OH)D level improved from 27.8 ng/mL at baseline to 33.6 ng/mL at week 26. Five patients (2.69% of the full analysis set) had 25(OH)D levels ≥ 50 ng/mL at 26 weeks. The highest 25(OH)D level, 64.3 ng/mL, was observed in a patient whose baseline level was 102.2 ng/mL. The majority (62.9%) of the patients had optimal 25(OH)D levels (30-50 ng/mL). β-CTx levels were reduced by 57.7% after 26 weeks' treatment. No clinically significant cases of hypercalcemia which could be associated with hypervitaminosis D were identified during physical examination, in vital signs, or in laboratory results. Overall, 73 patients (36.9%) reported at least one adverse event (AE), with 13 (6.6%) reporting drug-related AEs. Four patients discontinued due to AEs, two of which were drug-related. Serious AEs were reported for four patients, of which one was considered drug-related.ConclusionsOral alendronate sodium 70 mg plus vitamin D3 5600 IU once weekly had an acceptable safety profile in this study, and increased serum 25(OH)D and reduced β-CTx levels in osteoporosis patients. This treatment improved 25(OH)D levels, without causing abnormally high levels, after 26 weeks' treatment.Trial registrationClinical Trials.gov NCT01437111 , Registered September 19, 2011.

Project description:In this randomized, controlled trial, treatment with once-weekly subcutaneous injection of teriparatide for 72 weeks was found to be associated with a significant reduction in the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture.IntroductionTo determine whether the anti-fracture efficacy of teriparatide is superior to that of alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed.MethodsJapanese women aged at least 75 years were eligible for the study if they had primary osteoporosis and were at high risk of fracture. Patients were randomly assigned in a 1:1 ratio to receive sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint was the incidence of morphometric vertebral fractures at 72 weeks (at the end of teriparatide treatment).ResultsBetween October 2014 and December 2017, 1011 patients (505 in the teriparatide group and 506 in the alendronate group) were enrolled. Of these, 778 patients (351 and 427, respectively) were included in the primary analysis. The incidence of morphometric vertebral fractures was significantly lower in the teriparatide group (56 per 419.9 person-years, annual incidence rate 0.1334) than in the alendronate group (96 per 553.6 person-years, annual incidence rate 0.1734), with a rate ratio of 0.78 (95% confidence interval 0.61 to 0.99, P = 0.04). In both groups, adverse events were most frequently reported in the following system organ classes: infections and infestations, gastrointestinal disorders, and musculoskeletal and connective tissue disorders.ConclusionOnce-weekly subcutaneous injection of teriparatide significantly reduced the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture.Trial registrationjRCTs031180235 and UMIN000015573, March 12, 2019.

Dataset Information

Efficacy and safety of weekly alendronate plus vitamin D? 5600 IU versus weekly alendronate alone in Korean osteoporotic women: 16-week randomized trial.

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Efficacy and safety of weekly alendronate plus vitamin D₃ 5600 IU versus weekly alendronate alone in Korean osteoporotic women: 16-week randomized trial.

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