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Efficacy of risedronate with cholecalciferol on bone mineral density in Korean patients with osteoporosis.
Park, SY, Kang, MI, Park, HM, Rhee, Y, Moon, SH, Yoon, HK, Koh, JM, Chang, JS, Kim, IJ, Won, YY, et al
Archives of osteoporosis. 2019;(1):3
Abstract
UNLABELLED The efficacy of once-weekly risedronate with and without cholecalciferol in bone mineral density (BMD) in Korean patients with osteoporosis was compared. After 12 months, both spine and hip BMD increased significantly in both groups, but there was no significant difference between two groups. INTRODUCTION This study investigated the efficacy and safety of once-weekly risedronate with and without cholecalciferol in BMD in Korean patients with osteoporosis. METHODS This was a prospective, 12-month, randomized, open-labeled, actively controlled trial involving 41 hospitals. A total of 841 subjects with osteoporosis were randomized to once-weekly risedronate (35 mg) and cholecalciferol (5600 IU) in a single pill (RSD+, n = 642) or once-weekly risedronate (35 mg) alone (RSD, n = 199). BMD was measured via dual-energy X-ray absorptiometry at the lumbar spine and hip, and the serum levels of 25-hydroxy vitamin D (25(OH) D), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were assayed at baseline and after 12 months of treatment. RESULTS After 12 months, the lumbar spine, femoral neck, and total hip BMD increased significantly in both groups; there was no significant difference between two groups. Women in the RSD+ group exhibited significantly increased lumbar spine BMD, and subjects with previous fracture history in the RSD+ group had significantly increased total hip BMD compared with the RSD group. The serum 25(OH) D level increased significantly in the RSD+ group. The serum PTH level decreased in the RSD+ group but increased in the RSD group. The serum ALP level significantly decreased in both groups; there was no significant difference between two groups. CONCLUSIONS A once-weekly pill containing risedronate and cholecalciferol had the equivalent antiresorptive efficacy on BMD compared with risedronate alone and improved 25(OH) D serum levels after 12 months of treatment without significant adverse events in Korean patients with osteoporosis.
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Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study.
Bliuc, D, Tran, T, van Geel, T, Adachi, JD, Berger, C, van den Bergh, J, Eisman, JA, Geusens, P, Goltzman, D, Hanley, DA, et al
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(4):817-828
Abstract
UNLABELLED In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.
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Alendronate/Vitamin D for attenuating bone mineral density loss during antiretroviral initiation: a pilot randomized controlled trial.
Tan, DHS, Lee, T, Raboud, J, Qamar, A, Cheung, AM, Walmsley, S
HIV research & clinical practice. 2019;(6):140-150
Abstract
Background: Antiretroviral therapy (ART) initiation is associated with decreases in bone mineral density (BMD).Objectives: To plan for a larger trial, we sought to obtain preliminary estimates for the difference in the change in BMD at 48 weeks achieved with 24 weeks of prophylactic alendronate/vitamin D during ART initiation compared to no intervention, the within-group standard deviation of this change, and intra-patient correlation coefficient for repeated BMDs. Secondary objectives included assessing enrollment feasibility, treatment acceptability, adherence and safety.Methods: We randomized treatment-naïve HIV-positive adults initiating tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat or abacavir/lamivudine/dolutegravir 1:1:1 to immediate alendronate/vitamin D3 70 mg/5600 IU for 24 weeks (concomitant treatment arm, CTA), the same intervention starting 24 weeks after study entry (delayed treatment arm, DTA), or no bone anti-resorptive therapy (standard of care, SOC). We assessed BMD, acceptability, adverse events and drug adherence at baseline, week 24 and week 48.Results: Of 29 included participants, 72% initiated TDF/FTC/ELV/c and 28% initiated ABC/3TC/DTG. Median (IQR) CD4 count was 388 (303,525) cells/mm3 and median plasma HIV RNA was 4.45 (2.26, 4.84) log10 copies/mL. The mean (SD) percentage change in BMD for the CTA and DTA combined was 1.95% (2.53%), 0.38% (3.34%), and -0.57% (3.50%) at the lumbar spine, femoral neck and total hip respectively at 48 weeks. The ICC among repeated measurements of BMD was 0.978, 0.964, and 0.967 at these sites, respectively. Enrollment feasibility, drug acceptability, adherence, and tolerability were good.Conclusions: Our findings inform the sample size for a larger trial of bone anti-resorptive therapy during ART initiation and support feasibility.
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Prescribing and adherence to bone protection medications following hip fracture in the United Kingdom: results from the World Hip Trauma Evaluation (WHiTE) cohort study.
Cehic, M, Lerner, RG, Achten, J, Griffin, XL, Prieto-Alhambra, D, Costa, ML
The bone & joint journal. 2019;(11):1402-1407
Abstract
AIMS: Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group. PATIENTS AND METHODS The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants' discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery. RESULTS Of 5456 recruited patients with baseline data, 2853 patients (52%) were prescribed bone protection medication at discharge, of which oral bisphosphonates were the most common, 4109 patients (75%) were prescribed vitamin D or calcium, and 606 patients (11%) were not prescribed anything. Of those prescribed a bone protection medication, only 932 patients (33%) reported still taking their medication 120 days later. CONCLUSION These data provide a reference for current prescription and adherence rates. Adherence with oral medication remains poor in patients with hip fracture. Cite this article: Bone Joint J 2019;101-B:1402-1407.
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Novel Approach to Estimate Osteoarthritis Progression: Use of the Reliable Change Index in the Evaluation of Joint Space Loss.
Parsons, CM, Judge, A, Leyland, K, Bruyère, O, Petit Dop, F, Chapurlat, R, Reginster, JY, Edwards, MH, Dennison, EM, Cooper, C, et al
Arthritis care & research. 2019;(2):300-307
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OBJECTIVE Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression. METHODS Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. RESULTS Between consecutive years, 57-69% of participants had an apparent decrease (change <0) in JSW, while 31-43% of participants had annual changes indicating improvement in JSW. The RCI identified JSW decreases in only 6.0% of patients between baseline and year 1, and in 4.5% of patients between the remaining study years. The apparent increases in JSW were almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% of patients had a significant increase, dropping to 0.9% between years 2 and 3. CONCLUSION The RCI provides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSW from radiographs in clinical and research settings.
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Abaloparatide is an Effective Treatment Option for Postmenopausal Osteoporosis: Review of the Number Needed to Treat Compared with Teriparatide.
Reginster, JY, Hattersley, G, Williams, GC, Hu, MY, Fitzpatrick, LA, Lewiecki, EM
Calcified tissue international. 2018;(5):540-545
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Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 signaling pathway. In the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous ABL reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic fracture compared with placebo and of major osteoporotic fracture compared with teriparatide. To further evaluate the effectiveness of ABL, we calculated the number needed to treat (NNT) to prevent one fracture using ACTIVE data. To estimate the potential effectiveness of ABL in populations at higher fracture risk than in ACTIVE, we calculated NNT for vertebral fracture using reference populations from historical placebo-controlled trials, assuming an 86% relative risk reduction in vertebral fracture with ABL treatment as observed in ACTIVE. NNT was calculated as the reciprocal of the absolute risk reduction in ACTIVE. The projected NNT for ABL in other populations was calculated based on incidence rate (IR) for vertebral fractures in the placebo arms of the FREEDOM (placebo IR 7.2%), FIT-1 (placebo IR 15.0%), and FIT-2 (placebo IR 3.8%) trials. NNT for ABL in ACTIVE was 28 for vertebral, 55 for nonvertebral, 37 for clinical, and 34 for major osteoporotic fracture. NNT for these fracture types for teriparatide in ACTIVE were 30, 92, 59, and 75, respectively. Using placebo IRs from FREEDOM, FIT-1, and FIT-2, projected NNTs for vertebral fracture with ABL were 17, 8, and 31. These data are useful for further evaluating ABL for the treatment of osteoporosis in postmenopausal women.
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Clinical characteristics associated with bone mineral density improvement after 1-year alendronate/vitamin d3 or calcitriol treatment: Exploratory results from a phase 3, randomized, controlled trial on postmenopausal osteoporotic women in China.
Liao, EY, Zhang, ZL, Xia, WB, Lin, H, Cheng, Q, Wang, L, Hao, YQ, Chen, DC, Tang, H, Peng, YD, et al
Medicine. 2018;(31):e11694
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Baseline and on-treatment characteristics, including age, obesity, calcium intake, and bone turnover markers, may predict the bone mineral density (BMD) response in women with postmenopausal osteoporosis (PMO) to 1 to 2 years of antiresorptive therapy and/or vitamin D supplementation. This study aimed to explore clinical characteristics associated with 12-month BMD improvement in Chinese women with postmenopausal osteoporosis (PMO).In this post hoc analysis of a previous phase 3 multicenter, randomized controlled trial, Chinese PMO women who were treated with once weekly alendronate 70 mg/vitamin D3 5600 IU (ALN/D5600) or once daily calcitriol 0.25 mcg, and had measurements of 1-year lumbar spine BMD (LS-BMD) and on-treatment bone turnover markers (BTMs) were included in the analysis.In Chinese PMO patients on ALN/D5600, 1-year LS-BMD change was negatively correlated with age (β = -0.00084, P < .01), dietary calcium (β = -0.0017, P = .07), and procollagen type 1 N-terminal propeptide (P1NP) change at month 6 (β = -0.000469, P = .0016), but positively with body mass index (BMI) (β = 0.00128, P = .08); baseline P1NP above the median was associated with a significantly greater BMD percentage change at the lumbar spine (P = .02) and the total hip (P = .0001). In the calcitriol group, a significant 1-year LS-BMD increase was associated with BMI (β = 0.0023, P = .02), baseline P1NP (β = 0.00035, P = .0067), history of prior vertebral fracture(s) (β = 0.034, P < .0001) and baseline serum 25(OH)D level (β = -0.00083, P = .02).The presented findings from Chinese postmenopausal osteoporotic women suggested clinically meaningful baseline and on-treatment characteristics predicting BMD improvement after 1 year of ALN/D5600 treatment, which differed from calcitriol treatment with baseline identifiable associations. The study remained exploratory and further accumulation of evidence is needed.
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Open-label study of treatment with alendronate sodium plus vitamin D in men and women with osteoporosis in Thailand.
Songpatanasilp, T, Rojanasthien, S, Sugkraroek, P, Ongphiphadhanakul, B, Robert, L, Robert, CS, Luevitoonvechkij, S, Santora, AC
BMC musculoskeletal disorders. 2018;(1):392
Abstract
BACKGROUND It 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. METHODS Osteoporosis 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. RESULTS One 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. CONCLUSIONS Oral 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 REGISTRATION Clinical Trials.gov NCT01437111 , Registered September 19, 2011.
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Knee effusion-synovitis volume measurement and effects of vitamin D supplementation in patients with knee osteoarthritis.
Wang, X, Cicuttini, F, Jin, X, Wluka, AE, Han, W, Zhu, Z, Blizzard, L, Antony, B, Winzenberg, T, Jones, G, et al
Osteoarthritis and cartilage. 2017;(8):1304-1312
Abstract
OBJECTIVE To develop a measure of knee joint effusion-synovitis volume and to examine the effect of vitamin D supplementation on effusion-synovitis in people with knee osteoarthritis (OA) and low vitamin D levels over 24 months. METHOD Symptomatic knee OA patients with low 25-(OH)D levels (12.5-60 nmol/l) were recruited for a multi-centre, randomised, placebo-controlled and double-blind trial. Participants (age 63 ± 7 years, 208 females) were allocated to either 50,000 IU monthly vitamin D3 (n = 209) or placebo (n = 204) for 24 months. Knee effusion-synovitis volume in suprapatellar and other regions was measured on magnetic resonance imaging (MRI) using OsiriX software. The intra-class correlation coefficients (ICCs) were used to test inter- and intra-rater reliabilities. The least significant change criterion was used to define the increase/decrease in effusion-synovitis volume. RESULT The reproducibilities of effusion-synovitis volume measurement were high with ICCs ranging from 0.93 to 0.99. Over 24 months, effusion-synovitis volume remained stable in the vitamin D group but increased in placebos with a significant between-group difference (-1.94 ml, 95% confidence interval (CI): -3.54, -0.33). This effect was evident in those with baseline effusion-synovitis and with suprapatellar effusion-synovitis. The proportion with an increase in effusion-synovitis volume was lower in the vitamin D group than placebo (risk ratio (RR): 0.87, 95% CI: 0.77, 0.97). CONCLUSION This highly reproducible effusion-synovitis volume measurement could be a promising outcome measure in OA trials. Vitamin D supplementation could retard the progression of effusion-synovitis which can potentially benefit people with an inflammatory OA phenotype.
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Treatment of osteoporosis secondary to hypogonadism in prostate cancer patients: a prospective randomized multicenter international study with denosumab vs. alendronate.
Doria, C, Mosele, GR, Solla, F, Maestretti, G, Balsano, M, Scarpa, RM
Minerva urologica e nefrologica = The Italian journal of urology and nephrology. 2017;(3):271-277
Abstract
BACKGROUND Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT. METHODS A total of 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer were enrolled. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg/week) for 2 years. All patient received supplemental vitamin D (600 IU/day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), bone mineral density, fracture incidence, Visual Analogue Scale score for back pain, and Short Form-8 health survey score for health-related quality of life. RESULTS In the denosumab study group, level of BTMs for bone formation were significantly increased from baseline at all time points during the study (P<0.001); in the alendronate study group level of BTMs for bone formation were increased too (P>0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs. -1.1% with alendronate (P<0.001). CONCLUSIONS Denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.