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Vitamin D and Calcium Supplement Attenuate Bone Loss among HIVInfected Patients Receiving Tenofovir Disoproxil Fumarate/Emtricitabine/ Efavirenz: An Open-Label, Randomized Controlled Trial.
Boontanondha, P, Nimitphong, H, Musikarat, S, Ragkho, A, Kiertiburanakul, S
Current HIV research. 2020;(1):52-62
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BACKGROUND Antiretroviral therapy (ART), especially with tenofovir disoproxil fumarate (TDF), has been associated with accelerated bone turnover and leads to significant bone loss. OBJECTIVE We aimed to determine the effect of vitamin D2 and calcium on bone mineral density (BMD) in HIV-infected patients receiving TDF/emtricitabine (FTC)/efavirenz (EFV). METHODS A prospective, open-label, randomized controlled study was conducted. Eligible patients were ART naïve HIV individuals who initiated TDF/FTC/EFV. The study group received supplementation with vitamin D2 and calcium carbonate, whereas the control group was administered only ART. The primary outcome was the percentage change in total hip BMD at week 24 compared with baseline. RESULTS A total of 18 patients were randomized (9 in each group). The mean (standard deviation; SD) total hip BMD significantly decreased from baseline in both groups, from 0.96 (0.14) g/cm2 to 0.93 (0.13) g/cm2 in the study group (p = 0.006) and from 0.87 (0.11) g/cm2 to 0.84 (0.11) g/cm2 in the control group (p = 0.004). The mean (SD) lumbar spine BMD significantly decreased from baseline in both groups, from 1.00 (0.13) g/cm2 to 0.97 (0.13) g/cm2 (p = 0.004) in the study group and from 0.90 (0.09) g/cm3 to 0.86 (0.08) g/cm2 in the control group (p = 0.006). At week 24, the mean (SD) lumbar spine BMD was significantly greater in the study group than in the control group (p = 0.042). However, there were no significant differences in the percentage change of total hip, lumbar spine, and femoral neck BMD between both groups. No adverse events were reported. In conclusion, as early as 24 weeks after TDF initiation, a significant decline in BMD was detected. CONCLUSION Vitamin D2 and calcium supplements should be considered for HIV-infected patients receiving TDF/FTC/EFV in a resource-limited setting where there are limited ART options (Clinicaltrials. gov NCT0287643).
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Predictive Power of Bone Turnover Biomarkers to Estimate Bone Mineral Density after Kidney Transplantation with or without Denosumab: A post hoc Analysis of the POSTOP Study.
Heimgartner, N, Graf, N, Frey, D, Saleh, L, Wüthrich, RP, Bonani, M
Kidney & blood pressure research. 2020;(5):758-767
Abstract
BACKGROUND Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients. METHODS Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), β-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D. RESULTS Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment. CONCLUSIONS Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.
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Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four-Month Randomized, Double-Blind, Double-Dummy Trial.
Saag, KG, Pannacciulli, N, Geusens, P, Adachi, JD, Messina, OD, Morales-Torres, J, Emkey, R, Butler, PW, Yin, X, Lems, WF
Arthritis & rheumatology (Hoboken, N.J.). 2019;(7):1174-1184
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OBJECTIVE Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. METHODS This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of -2.0 or less (or -1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. RESULTS Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. CONCLUSION Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.
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Efficacy and safety of denosumab therapy for low bone mineral density in childhood cancer survivors: A report of preliminary experience.
Huang, TH, Liu, HC, Hou, JY, Chang, CY, Sun, FJ, Yeh, TC
Pediatric blood & cancer. 2019;(10):e27927
Abstract
BACKGROUND In childhood cancer survivors, low bone mineral density (BMD) is a bone-related consequence. Efficacy of denosumab, an effective therapy for adult patients with osteoporosis, remains unclear in children. This study aimed to investigate denosumab therapy efficacy for low BMD in childhood cancer survivors. PROCEDURE Between January 2014 and January 2018, we monitored lumbar BMD of children with cancer using dual-energy X-ray absorptiometry after completing chemotherapy with a 6-month interval. For patients with low BMD, defined as height-adjusted Z-scores of BMD < -1.5 in this study, calcium carbonate and vitamin D supplements were initially administered. When low BMD continued for at least 6 months, denosumab therapy was introduced. Calcium and vitamin D supplementation were continued in patients on denosumab. We investigated BMD change and adverse effects during denosumab therapy. RESULTS During the study period, 20 patients received denosumab treatment. Mean height-adjusted Z-score of BMD before denosumab treatment was -2.68 but increased to -2, -1.96, and -1.33 at 0.5, 1, and 1.5 years after denosumab treatment, respectively (P = .012). In addition, hypocalcemia occurred in 40% (8/20) of patients; three patients had hypocalcemic symptoms with numbness in all four limbs. All hypocalcemic patients, except one patient who died due to relapsed leukemia, recovered well after continuous calcium supplementation. CONCLUSIONS Denosumab is an effective treatment for low BMD in childhood cancer survivors. However, the complication of hypocalcemia might develop posttreatment.
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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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Calcitriol treatment in patients with low vitamin D levels.
Tanakol, R, Gül, N, Üzüm, AK, Aral, F
Archives of osteoporosis. 2018;(1):114
Abstract
UNLABELLED The aim of the the study is to compare the effects of cholecalciferol and calcitriol on bone mineral metabolism in women with vitamin D deficiency. Calcitriol was associated with a significant increase in bone mineral density at the lumbar spine in patients with low vitamin D levels. PURPOSE/INTRODUCTION Active vitamin D analogs may have larger impact in decreasing bone loss and fracture rate compared to cholecalciferol in osteoporosis. However, their effects in the treatment of vitamin D deficiency compared to cholecalciferol are not clear. The aim of the present study is to compare the effects of cholecalciferol and calcitriol on bone mineral metabolism and bone mineral density in pre- and postmenopausal women with vitamin D deficiency. METHODS This was a 6-month prospective, open-label, controlled clinical trial. Eligible 120 participants were pre- and postmenopausal women diagnosed with vitamin D deficiency. Forty-three subjects (group 1) received 1000 IU of cholecalciferol and 1 g of calcium daily. The other 77 subjects (group 2) received 0.5 μg calcitriol in addition to 400 IU of cholecalciferol and 1 g of calcium daily. RESULTS Oral vitamin D supplementation did not increase bone mineral density after 6 months of intervention in group 1. On the other hand, bone mineral density at the lumbar spine increased from 0.809 ± 0.172 to 0.848 ± 0.161 g/cm2 in group 2 patients (p < 0.017 vs baseline). CONCLUSIONS Oral daily calcitriol was associated with a significant increase in bone mineral density at the lumbar spine in patients with low vitamin D, elevated PTH, and osteoporosis.
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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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Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.
D'Eufemia, P, Finocchiaro, R, Zambrano, A, Lodato, V, Celli, L, Finocchiaro, S, Persiani, P, Turchetti, A, Celli, M
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2017;(1):339-346
Abstract
UNLABELLED This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. INTRODUCTION The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. METHODS This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. RESULTS Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. CONCLUSIONS This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.
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Effect of alfacalcidol on the pulmonary function of adult asthmatic patients: A randomized trial.
Ali, AM, Selim, S, Abbassi, MM, Sabry, NA
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2017;(5):557-563
Abstract
BACKGROUND Despite the use of alfacalcidol in the management of corticosteroid-induced osteoporosis, it has never been considered an adjunct treatment for asthma management. It can target vitamin D deficiency, a possible risk factor for asthma, and, hence, improve pulmonary function of patients with asthma. OBJECTIVE To explore the effect of alfacalcidol administration on pulmonary function and study the pattern of vitamin D deficiency in adults with asthma in Egypt. METHODS Serum 25-hydroxyvitamin D was measured in 115 adults: 33 healthy subjects and 82 patients with asthma. Then, patients with asthma were randomized to receive standard asthma treatment only (n = 39) or receive it in addition to 1 μg of alfacalcidol daily for 4 months (n = 43). Randomization was stratified by the stage of asthma severity. Spirometry and measurement of 25-hydroxyvitamin were performed at baseline and end of follow-up. RESULTS Vitamin D deficiency was more common in patients with asthma (57.3%) than in healthy subjects (21.2%; P < .001). In patients with asthma, alfacalcidol significantly improved forced expiratory volume in the first second and forced vital capacity (P < .001 for the 2 tests). Moreover, more patients in the intervention arm showed improvement in asthma severity stage (P = .04). A nonsignificant difference was observed in improvement of forced expiratory volume in the first second between patients with vitamin D deficiency and those without deficiency in the intervention group (P > .05). CONCLUSION Alfacalcidol supplementation improved the pulmonary function and severity stage of adult patients with asthma regardless of deficiency. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02747381.