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Citrate dose for continuous hemofiltration: effect on calcium and magnesium balance, parathormone and vitamin D status, a randomized controlled trial.
Boer, W, Fivez, T, Vander Laenen, M, Bruckers, L, Grön, HJ, Schetz, M, Oudemans-van Straaten, H
BMC nephrology. 2021;(1):409
Abstract
BACKGROUND Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D. METHODS Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325-0.4 mmol/L vs. 0.2-0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D). RESULTS 35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs - 1.18 mmol/d (se 1.70)) (p = 0.002) in the low citrate group and 24-h Mg-balance was - 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d (p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th-75th percentile 140-384) to 162 (111-265) pg/ml (p = 0.002); oxPTH from 192 (124-353) to 154 pg/ml (87-231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l (p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml (p = 0.046), without differences between groups. CONCLUSIONS A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group. TRIAL REGISTRATION ClinicalTrials.gov : NCT02194569. Registered 18 July 2014.
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Effect of calcitriol combined with sevelamer carbonate on serum parathyroid hormone in patients with chronic renal failure.
Zheng, H, Liu, Z
Cellular and molecular biology (Noisy-le-Grand, France). 2020;(2):31-35
Abstract
This study aimed to observe and analyze the effect of calcitriol combined with sevelamer carbonate on serum parathyroid hormone in patients with chronic renal failure. This study included 180 patients who had been treated for chronic renal failure in our hospital were enrolled as research objects. The patients were randomly divided into two groups: a research group and a control group, each containing 90 cases. The research group was treated with calcitriol combined with sevelamer carbonate, and the control group was treated with calcitriol alone. The therapeutic effects of the two groups were observed and analyzed by SPSS 21. Comparing the levels of blood indexes (Ca, Cr, P, ALP, iPTH, TC, TG, LDL-C, HDL-C) of the two groups showed no significant difference between the two groups, P <0.05. Our results have the effect of different treatment regimens, the improvement effect of various blood indicators in the research group was significantly better than the control group, p<0.05. We concluded that the combined therapy of calcitriol and sevelamer carbonate in chronic renal failure patients can significantly improve the therapeutic effect, and at the same time actively improve the serum parathyroid hormone level, which is a treatment model that can be popularized and applied.
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Identifying early postoperative serum parathyroid hormone levels as predictors of hypocalcaemia after total thyroidectomy: A prospective non-randomized study.
Košec, A, Hergešić, F, Matovinović, F, Rašić, I, Vagić, D, Bedeković, V
American journal of otolaryngology. 2020;(3):102416
Abstract
OBJECTIVE There is no clear cut-off value of serum parathyroid hormone (PTH) or calcium in which patients are at risk for hypocalcemia after total thyroidectomy. We evaluated the usefulness of serum calcium and PTH concentration measurements after total thyroidectomy in predicting late-occurring hypocalcemia. DESIGN A prospective, single-center, non-randomized longitudinal cohort study of 143 patients undergoing thyroidectomy between August 2019 and December 2019 with serum calcium and PTH levels sampled 1 h after surgery and on the first and fifth postoperative day. Hypocalcemia was defined as serum calcium levels < 2.14 mmol/L regardless of clinical symptoms. Normal PTH range was 1.6-6.9 pmol/L. MEASUREMENTS The primary outcome measure was presence of hypocalcemia on the first and fifth postoperative day, analyzed by a logistic regression model. The PTH cut-off value for prediction of hypocalcemia was identified using a ROC curve comparing all three time points using the Youden J index. RESULTS Out of 143 patients, 52 (36.4%) had hypocalcemia on the fifth postoperative day. Advanced age, concomitant neck dissection and serum PTH levels < 2.9 pmol/L 1 h after surgery and on the first postoperative surgery day were associated with a high risk of hypocalcemia on the first and fifth postoperative day and need for higher doses of calcium supplements (P < 0.0001, AUC 0.748, 95% CI 0.669-0.817, with 76.92% sensitivity and 71.43% specificity). CONCLUSION Serum PTH level measured immediately postoperatively and on the first postoperative day is a reliable predictor of postoperative hypocalcemia with important clinical implications.
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Paradoxical Response of Parathyroid Hormone to Vitamin D-Calcium Supplementation in Indian Children.
Mandlik, RM, Mughal, ZM, Khadilkar, AV, Ekbote, VH, Kajale, NA, Patwardhan, VG, Khadilkar, VV, Padidela, R
The Journal of pediatrics. 2020;:197-203
Abstract
OBJECTIVES To investigate the effect of oral vitamin D-calcium supplementation on serum intact parathyroid hormone (PTH), calcium, phosphorous, and alkaline phosphatase (ALK-P) concentrations in children with habitually low calcium intakes. STUDY DESIGN In this follow-up study to a randomized controlled trial that aimed to assess the effect of vitamin D-calcium supplementation on immunity, data related to dietary intake, anthropometry, and biochemistry [serum 25(OH)D and bone profile] were collected from 178 children-79 in the vitamin D group and 99 in the non-vitamin D group. RESULTS Dietary calcium to phosphorus intake ratio was 0.4:1. Baseline serum 25(OH)D concentration was 58.2 ± 10.9 nmol/L; 66% children were vitamin D sufficient and none deficient. After supplementation, vitamin D group, compared with the non-vitamin D group, had significantly (P < .05) greater 25(OH)D (83.9 ± 30.1 nmol/L vs 58.3 ± 15.7 nmol/L), significantly greater PTH (6.7 ± 3.6 pmol/L vs 5.5 ± 3.2 pmol/L), and positive correlation (rs = 0.24) between serum 25(OH)D and PTH (vs negative correlation [rs = -0.1] in non-vitamin D group). Mean concentrations of serum bone measures in the vitamin D group were calcium (2.2 ± 0.1 mmol/L), phosphorus (1.7 ± 0.2 mmol/L), and ALK-P (178.7 ± 40.7 IU/L). At follow-up, 1-year post-supplementation, in the vitamin D group, PTH concentrations continued to remain high (but not significantly different from levels at 6 months), with low normal serum calcium, high normal phosphate, and ALK-P in reference range. CONCLUSIONS In children who are vitamin D sufficient but with habitually low dietary calcium intake, vitamin D-calcium supplementation paradoxically and significantly increased serum PTH concentrations with no apparent effect on other bone biochemistry. Chronic low dietary calcium to phosphorus ratio is likely to have caused this paradoxical response.
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Effects of vitamin D3 supplementation for 12 weeks on serum levels of anabolic hormones, anaerobic power, and aerobic performance in active male subjects: A randomized, double-blind, placebo-controlled trial.
Ramezani Ahmadi, A, Mohammadshahi, M, Alizadeh, A, Ahmadi Angali, K, Jahanshahi, A
European journal of sport science. 2020;(10):1355-1367
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Abstract
Maintenance of the serum 25-hydroxyvitamin D (25-OH-D) concentration at recommended levels is essential due to its role in the regulation of anabolic hormones and athletic performance. However, the results of the clinical experiments in athletes are controversial. The present study aimed to investigate the effect of vitamin D3 supplement on serum levels of anabolic hormones, cortisol, anaerobic and aerobic performance in active males. In this double-blind, randomized controlled trial, 46 active males randomly assigned to vitamin D3 supplement (VDS; 2000 IU/day) or placebo for 12 weeks. The Wingate test, VO2max, and serum levels of 25-OH-D, Parathyroid hormone (PTH), total testosterone, growth hormone (GH), Insulin-like growth factor-1 (IGF-1), and cortisol were assessed. Subjects in the VDS group had a higher serum level of 25-OH-D (p = 0.004), VO2max (p = 0.016), and average power (p = 0.044) compared to the placebo at the end of the study. Also, lower levels of PTH (p = 0.004) and fatigue index (p < 0.001) were observed in VDS group at the end of the study. The serum cortisol levels were reduced significantly only in subjects with vitamin D deficiency in VDS group (p = 0.042). There was a significant reduction in serum testosterone levels in VDS group (p = 0.013). No change was indicated in serum levels of GH and IGF-1 in VDS group compared to the placebo (p > 0.05). The present study showed an improvement in aerobic capacity, anaerobic performance, and vitamin D status following vitamin D3 supplementation. However, more studies are required for the effect of vitamin D3 on serum concentration of anabolic hormones.
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Changes in serological bone turnover markers in bisphosphonate induced osteonecrosis of the jaws: A case control study.
Demircan, S, Isler, SC
Nigerian journal of clinical practice. 2020;(2):154-158
Abstract
BACKGROUND There are a lot study confirmed the relationship of bone serum markers changes and skeletal irregularities. But there is no sufficient case control studies about the role of these markers on bisphosphonate induced osteonecrosis of jaws (BRONJ). AIMS The aim of this study is to find out if there is any derangement of bone markers in bisphosphonate-treated patients with ONJ. METHODS We obtained serum bone markers and other relevant endocrine assays on 20 patients with osteonecrosis of the jaw (ONJ) and 20 randomized healthy volunteers. All of the ONJ group treated with zoledronic acid and had been withdrawn from bisphosphonate for at least 6 months. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. The biochemical assays were performed on N-Telopeptides of type I collagen (NTX), bone-specific alkaline phosphatase (ALP), calcitonin, osteocalcin, intact parathyroid hormone (PTH), T3, T4, TSH, and Vitamin D 25 hydroxy (Vit-D). RESULTS In ONJ group, PTH level is statistically higher and TSH, Vit-D, osteocalcin and NTX levels statistically lower compared to control group. CONCLUSION We conclude that these changes in PTH, Vit-D, TSH, osteocalcin and NTX levels maybe have a role in the pathophysiology of BRONJ. But the data need to be confirmed by future studies.
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FGF23 and the PTH response to paricalcitol in chronic kidney disease.
D'Arrigo, G, Pizzini, P, Cutrupi, S, Tripepi, R, Tripepi, G, Mallamaci, F, Zoccali, C
European journal of clinical investigation. 2020;(2):e13196
Abstract
BACKGROUND The parathyroid glands are endowed both with receptors responsive to FGF23 and to 1,25 vitamin D. Vitamin D receptor (VDR) activation, besides lowering PTH, also raises serum FGF23. FGF23 has been implicated in parathyroid resistance to VDR activation but the issue has never been investigated in predialysis CKD patients. METHODS In the Paricalcitol and Endothelial Functio in Chronic Kidney Disease (PENNY) study (NCT01680198), a 12-week randomized trial in stage G3-4 CKD patients (placebo n = 44 and paricalcitol n = 44), we measured PTH and the active form of FGF23 with no missing value across the trial. RESULTS At baseline, serum FGF23 and PTH were inter-related (r = .54, P < .01). Paricalcitol reduced serum PTH (-75.1 pg/mL, 95% CI: -90.4 to -59.8; P < .001) and increased FGF23 (+107 pg/mL, 95% CI: 44-170 pg/mL, P = .001). Changes in the Ca × P product in response to paricalcitol were closely related to simultaneous FGF23 changes in an analysis adjusted for changes in serum calcium and phosphate (P < .001). Of note, baseline FGF23, appropriately adjusted for baseline PTH, was unrelated with the PTH response to paricalcitol (r = -.06, P = .72). Placebo did not change neither PTH nor FGF23. CONCLUSION Serum FGF23 and PTH are inter-related and changes in the Ca × P product induced by paricalcitol per se correlate with the FGF23 response to this drug. Independently of serum FGF23, the parathyroid glands of patients with moderate to severe CKD maintain an intact ability to respond to VDR activation.
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Associations Between Change in Total and Free 25-Hydroxyvitamin D With 24,25-Dihydroxyvitamin D and Parathyroid Hormone.
Shieh, A, Ma, C, Chun, RF, Wittwer-Schegg, J, Swinkels, L, Huijs, T, Wang, J, Donangelo, I, Hewison, M, Adams, JS
The Journal of clinical endocrinology and metabolism. 2018;(9):3368-3375
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CONTEXT The physiologic role of free 25-hydroxyvitamin D [25(OH)D] in humans is unclear. OBJECTIVE To assess whether rise in total vs free 25(OH)D is associated with change in downstream biomarkers of 25(OH)D entry into target cells in kidney and parathyroid: 24,25-dihyroxyvitamin D [24,25(OH)2D] and PTH, respectively. DESIGN 16-week randomized controlled trial. INTERVENTION 60 μg (2400 IU)/d of D3 or 20 μg/d of 25(OH)D3. SETTING Academic medical center. PARTICIPANTS 35 adults age ≥18 years with 25(OH)D levels < 20 ng/mL. MAIN OUTCOME MEASURES 24,25(OH)2D, 1,25-dihyroxyvitamin D [1,25(OH)2D] and PTH. RESULTS At baseline, participants [D3 and 25(OH)D3 groups combined] were 35.1 ± 10.6 years. Mean total 25(OH)D, free 25(OH)D, 24,25(OH)2D, and PTH were 16.6 ng/mL, 4.6 pg/mL, 1.3 ng/mL, and 37.2 pg/mL, respectively. From 0 to 4 weeks, rise in only free 25(OH)D was associated with a concurrent 24,25(OH)2D increase [P = 0.03, adjusted for change in 1,25(OH)2D and supplementation regimen] and PTH decrease (P = 0.01, adjusted for change in calcium and supplementation regimen). Between 4 and 8 weeks, and again from 8 to 16 weeks, rises in free and total 25(OH)D were associated with 24,25(OH)2D increase; in contrast, rise in neither total nor free 25(OH)D was associated with PTH decrease during these time periods. CONCLUSIONS Early rise in free 25(OH)D during treatment of vitamin D deficiency was more strongly associated with changes in biomarkers of 25(OH)D entry into target kidney and parathyroid cells, suggesting a physiologic role of free 25(OH)D in humans.
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Effects of Different Dietary Interventions on Calcitriol, Parathyroid Hormone, Calcium, and Phosphorus: Results from the DASH Trial.
Hassoon, A, Michos, ED, Miller, ER, Crisp, Z, Appel, LJ
Nutrients. 2018;(3)
Abstract
The "Dietary Approaches to Stop Hypertension" (DASH) diet, rich in fiber and low-fat dairy, effectively lowers blood pressure. DASH's effect on calcitriol and other markers of bone-mineral metabolism is unknown. This secondary analysis of the DASH trial aimed to determine the effect of dietary patterns on blood concentrations of calcitriol, parathyroid hormone (PTH), ionized calcium, and urinary excretion of calcium and phosphorus. Outcomes were available in 334 participants in the trial. After a 3-week run-in on the control diet, participants were randomized to control, fruits and vegetables (F&V), or DASH diets. Outcomes were assessed at the end of run-in, and during the last week of the intervention period. Mean age of participants was 45.7 ± 10.7 years, 46% female, and 57% African-American. Mean ± Standard Deviation(SD) baseline serum concentrations of calcitriol, PTH, and ionized calcium were 37.8 ± 9.2 pg/mL, 46.1 ± 18.5 pg/mL and 5.2 ± 0.23 mg/dL, respectively. Mean (±SD) urinary calcium and phosphorus excretions were 150.1 ± 77.8 and 708.0 ± 251.8 mg/24 h, respectively. Compared with control, DASH reduced calcitriol -3.32 pg/mL (p = 0.004). Otherwise, there was no significant effect on other biomarkers. DASH lowered serum calcitriol perhaps more among African-Americans. These results raise important questions about the interpretation and clinical significance of low calcitriol concentrations in the setting of recommended diets.
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Effect of calcium citrate vs calcium carbonate on elevated parathyroid hormone after Roux-en-Y gastric bypass. A double-blinded, randomized trial.
Ring Madsen, L, Espersen, R, Rejnmark, L, Richelsen, B
Clinical endocrinology. 2018;(6):734-741
Abstract
OBJECTIVE Following Roux-en-Y gastric bypass (RYGB), elevated parathyroid hormone (PTH) levels potentially harmful to bone health are commonly observed. Owing to assumed superior absorption, calcium citrate is often recommended over calcium carbonate following RYGB for the treatment of elevated PTH. We aimed to investigate the impact of either calcium carbonate or calcium citrate (1200 mg elementary calcium) in patients with elevated PTH levels following RYGB. DESIGN Clinical, double-blinded, randomized controlled trial of a 12-week duration at a Danish University Hospital. PATIENTS AND MEASUREMENTS Thirty-nine (no drop out) RYGB operated patients with elevated PTH levels (PTH > 6.9 pmol/L) and normal plasma levels of calcium and 25-hydroxyvitamin D were randomized to either calcium carbonate or calcium citrate (1200 mg elementary calcium/daily). We assessed change in PTH as the primary outcome. RESULTS The effect of the two calcium formulations on change in PTH was comparable and neutral: -1.9% (calcium citrate) vs +0.9% (calcium carbonate), P = 0.680. Compared to the carbonate-treated group, the following bone turnover markers decreased significantly in the citrate-treated group: procollagen I N-terminal propeptide (-16.6% vs -3.2%, P = 0.021), osteocalcin (-17.2% vs -4.3%, P = 0.007) and bone-specific alkaline phosphatase (-5.9% vs 3.7%, P = 0.027) and remained significantly decreased after multivariable adjustment. CONCLUSION Increasing the dose of calcium supplementation in RYGB operated patients with slightly elevated PTH levels does not normalize PTH levels, regardless of the type of supplement. Our results do not support recommending supplementation with calcium citrate over calcium carbonate in RYGB patients.