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JAMA Network Open Apr 2022Several health benefits of vitamin D have been suggested; however, the safety of high-dose supplementation in early childhood is not well described. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Several health benefits of vitamin D have been suggested; however, the safety of high-dose supplementation in early childhood is not well described.
OBJECTIVE
To systematically assess the risk of adverse events after high-dose supplementation with vitamin D reported in published randomized clinical trials.
DATA SOURCES
PubMed and ClinicalTrials.gov were searched through August 24, 2021.
STUDY SELECTION
Randomized clinical trials of high-dose vitamin D supplementation in children aged 0 to 6 years, defined as greater than 1000 IU/d for infants (aged 0-1 year) and greater than 2000 IU/d for children aged 1 to 6 years.
DATA EXTRACTION AND SYNTHESIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 reviewers independently extracted the data from the eligible studies. Summary risk ratio (RR), 95% CI, and P values were derived from random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
Adverse events, serious adverse events (SAEs), and/or levels of 25-hydroxyvitamin D, calcium, alkaline phosphatase, phosphate, parathyroid hormone, and/or the ratio of urine calcium to creatinine levels.
RESULTS
A total of 32 randomized clinical trials with 8400 unique participants were included. Different clinical outcomes of children receiving high-dose vitamin D supplements ranging from 1200 to 10 000 IU/d and bolus doses from 30 000 IU/week to a single dose of 600 000 IU were evaluated. Eight studies with 4612 participants were eligible for meta-analysis using a control group receiving either low-dose vitamin D supplementation (≤400 IU/d) or placebo when investigating the risk of SAEs such as hospitalization or death. No overall increased risk of SAEs in the high-dose vitamin D vs control groups was found (RR, 1.01 [95% CI, 0.73-1.39]; P = .89, I2 = 0%). In addition, risk of hypercalcemia (n = 726) was not increased (RR, 1.18 [95% CI, 0.72-1.93]; P = .51). Clinical adverse events potentially related to the vitamin D supplementation reported in the studies were rare.
CONCLUSIONS AND RELEVANCE
This meta-analysis and systematic review found that high-dose vitamin D supplementation was not associated with an increased risk of SAEs in children aged 0 to 6 years, and that clinical adverse events potentially related to the supplementation were rare. These findings suggest that vitamin D supplementation in the dose ranges of 1200 to 10 000 IU/d and bolus doses to 600 000 IU to young children may be well tolerated.
Topics: Calcium; Child; Child, Preschool; Dietary Supplements; Humans; Infant; Randomized Controlled Trials as Topic; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 35420658
DOI: 10.1001/jamanetworkopen.2022.7410 -
Scientific Reports Feb 2022Chronic Pb exposure associated systemic illness are partly posited to involve calcium homeostasis. Present systematic review aims to comprehensively evaluate the... (Meta-Analysis)
Meta-Analysis
Chronic Pb exposure associated systemic illness are partly posited to involve calcium homeostasis. Present systematic review aims to comprehensively evaluate the association between chronic lead exposure and markers of calcium homeostasis. Observational studies documenting the changes in calcium homeostasis markers (i.e. serum calcium, parathyroid hormone, vitamin D & calcitonin) between occupationally Pb exposed group and control group were systematically searched from pubmed-Medline, Scopus, and Embase digital databases since inception to September 24, 2021. The protocol was earlier registered at PROSPERO (ID: CRD42020199503) and executed adhering to PRISMA 2020 guidelines. Mean differences of calcium homeostasis markers between the groups were analysed using random-effects model. Conventional I statistics was employed to assess heterogeneity, while the risk for various biases were assessed using Newcastle Ottawa Scale. Sub-group, sensitivity and meta-regression analyses were performed where data permitted. Eleven studies including 837 Pb exposed and 739 controls were part of the present study. Pb exposed group exhibited higher mean blood lead level [i.e. 36.13 (with 95% CI 25.88-46.38) µg/dl] significantly lower serum calcium (i.e. - 0.72 mg/dl with 95% CI - 0.36 to - 1.07) and trend of higher parathyroid levels and lower vitamin D levels than controls. Heterogeneity was high (I > 90%) among the studies. Considering the cardinal role of calcium in multiple biological functions, present observations emphasis the need for periodic evaluation of calcium levels and its markers among those with known cumulative Pb exposure.
Topics: Adult; Biomarkers; Calcitonin; Calcium; Female; Homeostasis; Humans; Lead; Lead Poisoning; Male; Middle Aged; Observational Studies as Topic; Occupational Exposure; Parathyroid Hormone; Vitamin D; Young Adult
PubMed: 35115666
DOI: 10.1038/s41598-022-05976-4 -
Clinical Therapeutics Jan 2022The efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to... (Meta-Analysis)
Meta-Analysis
PURPOSE
The efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to determine comparative effectiveness. This study was the first to investigate the impact of time point-specific NMAs of osteoporosis treatments on variability in treatments' onset of action caused by their different mechanisms of actions and trial designs.
METHODS
A systematic literature review was conducted to identify randomized controlled trials (RCTs) of treatments for postmenopausal women with osteoporosis, including romosozumab (ROMO), teriparatide (TPTD), abaloparatide (ABL), alendronate (ALN), risedronate (RIS), ibandronate (IB), zoledronic acid/zoledronate (ZOL), denosumab (DEN), and raloxifene (RLX), on at least 1 fracture or bone mineral density (BMD) outcome. Of 100 RCTs identified in 5 databases, 27 RCTs were included for NMAs of new vertebral, nonvertebral, and hip fracture outcomes at 12, 24, and 36 months, and 47 RCTs were included for NMAs of BMD outcomes at lumbar spine, total hip, and femoral neck to compare the relative efficacy of osteoporosis treatments. Quality of included studies was assessed using the Cochrane Risk of Bias tool.
FINDINGS
For vertebral fractures, TPTD (83.63%), ABL (69.11%), and ROMO/ALN (78.70%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO/ALN had the highest probability (54.4%, 64.69%, and 90.29%, respectively) to be the most effective treatment for nonvertebral fractures at 12, 24, and 36 months. For hip fractures, ROMO/ALN (46.31%), ABL (61.1%), and DEN (55.21%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO had the highest probability (76.06%, 44.19%, and 51.78%, respectively) to be the most effective treatment for BMD outcomes at lumbar spine, total hip, and femoral neck.
IMPLICATIONS
The importance of indirectly comparing available osteoporosis treatments using time point-specific NMAs was confirmed because indirect comparison results differed substantially across time points.
Topics: Bone Density; Bone Density Conservation Agents; Female; Humans; Network Meta-Analysis; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Teriparatide; Zoledronic Acid
PubMed: 35058055
DOI: 10.1016/j.clinthera.2021.11.015 -
European Review For Medical and... Jan 2022The data on the treatment of secondary hyperparathyroidism (SHPT) provided in scientific publications are divergent and contradictory. Therefore, the aim of our...
OBJECTIVE
The data on the treatment of secondary hyperparathyroidism (SHPT) provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of SHPT treatment in (chronic kidney disease) CKD.
MATERIALS AND METHODS
The Cochrane, PubMed, and Scopus databases were searched independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness and side effects of calcifediol, ergocaliferol, calcitriol, paricalcitol, and cinacalcet were compared and analyzed.
RESULTS
Extended-release (ER) calcifediol raised the total serum 25-hydroxyvitamin D level over the threshold of 30 ng/mL in 80% of the patients analyzed in the study. It is the level required for intact PTH (iPTH) suppression. ER calcifediol reduced the iPTH level by 30% in about 30% of the patients, whereas only 2.1% of them had hypercalcemia. Calcitriol significantly decreased the iPTH values. It was the cause of hypercalcemia in 1.7% of the patients. The reduction of the iPTH level by more than 30% was observed in 85.7% of the patients in the paracalcitol group after 48-week supplementation. Paricalcitol was the cause of hypercalcemia in 1.9% of the patients. The cinacalcet therapy resulted in the highest percentage of patients with the iPTH level within the limits recommended by the KDOQI (70-110 ng/L for stage 4 CKD and 150-300 ng/L for stage 5 CKD). 92% of the patients met the KDOQI guidelines and the mean decrease in the serum iPTH level was 68%.
CONCLUSIONS
Calcifediol ER, paricalcitol, and cinacalcet significantly decreased the iPTH level in the patients under study. Paricalcitol increased the serum calcium concentration the most of all the drugs under analysis. It is noteworthy that only cinacalcet does not carry the risk of hypercalcemia.
Topics: Calcitriol; Calcium; Cinacalcet; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 35049000
DOI: 10.26355/eurrev_202201_27773 -
Stomatologija 2022To systematically review the current literature and determine whether the additional TPTD administration for patients with BRONJ is an effective treatment modality.
OBJECTIVE
To systematically review the current literature and determine whether the additional TPTD administration for patients with BRONJ is an effective treatment modality.
MATERIAL AND METHODS
The systematic review was registered in the PROSPERO (CRD42021242796) and conducted according to the PRISMA statement. An electronic search was performed using MEDLINE (PubMed), ScienceDirect, The Cochrane Library and LILACS databases using a combination of the keywords "Bisphosphonate-Associated Osteonecrosis of the Jaw"[Mesh], "treatment" to identify studies published from 2010.
RESULTS
The authors found 8 articles that met the inclusion criteria of this systematic review. According to two studies, TPTD was statistically significantly associated with a greater BRONJ lesion resolution, compared to control group (p<0.05). However, one article showed no significant difference in proportion of resolved lesions (p=0.478). Regarding the effectiveness of TPTD treatment according to administration frequency, daily injection group showed no significant changes in the clinical stage of BRONJ, no difference in the percentage of bone formation on patients osteolysis, compared to weekly injections. Concerning bone resorption/regeneration markers, all the included studies showed that bone resorption markers significantly increased after 3-month TPTD administration. In a study which used multivariate analysis between TPTD and non-TPTD groups using age, BMI, duration of BP usage, the difference in s-OC values after 3 months of the treatment was significant (p<0.05).
CONCLUSION
This review provides evidence for the potential benefits of additional TPTD administration for patients with BRONJ being an effective treatment modality.
Topics: Humans; Infant; Teriparatide; Bisphosphonate-Associated Osteonecrosis of the Jaw; Treatment Outcome; Bone Resorption; Bone Density Conservation Agents
PubMed: 37140255
DOI: No ID Found -
Clinical Kidney Journal Nov 2021This study evaluates the effects of active (1α-hydroxylated) vitamin D (AVD) therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and...
Active vitamin D increases the risk of hypercalcaemia in non-dialysis chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis.
BACKGROUND
This study evaluates the effects of active (1α-hydroxylated) vitamin D (AVD) therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and secondary hyperparathyroidism (SHPT).
METHODS
A systematic search of the PubMed, Embase and Cochrane Library databases (up to 14 May 2020) was performed to identify randomized, placebo-controlled trials of single-agent, oral AVD therapies in adults with ND-CKD and SHPT. Only studies with ≥30 participants per arm and ≥6 weeks in duration were eligible. The outcome of interest was the number of subjects with an episode of hypercalcaemia. A meta-analysis of eligible studies was conducted using Comprehensive Meta-Analysis software (version 3.0).
RESULTS
Six studies (five evaluating paricalcitol, one evaluating alfacalcidol) involving 799 patients were identified. Treatment durations ranged from 16 weeks to 2 years. The weekly doses of paricalcitol administered were 7 (three studies) and 14 µg (two studies); the weekly dose of alfacalcidol was 1.75-7.0 µg. Across all studies, rates of hypercalcaemia were 1.1-43.3% with AVD versus 0-3.4% with placebo. Meta-analysis of the six studies showed that AVD was associated with a 6.6-fold greater probability of hypercalcaemia versus placebo (odds ratio: 6.63, 95% confidence interval: 2.37, 18.55; P < 0.001). Two separate sensitivity analyses (one excluded a study identified as having a high risk of bias; the second excluded two studies that accounted for a large proportion of observed hypercalcaemia events) indicated the primary meta-analysis findings were robust.
CONCLUSIONS
Compared with placebo, AVD significantly increased the risk of hypercalcaemia among ND-CKD patients with SHPT.
PubMed: 34754440
DOI: 10.1093/ckj/sfab091 -
Cureus Oct 2021Nowadays, chronic kidney disease (CKD) and osteoporosis have become crucial health-related issues globally. CKD-induced osteoporosis is a systemic disease characterized... (Review)
Review
Nowadays, chronic kidney disease (CKD) and osteoporosis have become crucial health-related issues globally. CKD-induced osteoporosis is a systemic disease characterized by the disruption of mineral, hormone, and vitamin homeostasis that elevates the likelihood of fracture. Here, we review recent studies on the association of CKD and osteoporosis. In particular, we focus on the pathogenesis of CKD-associated osteoporosis, including the homeostasis and pathways of several components such as parathyroid hormone, calcium, phosphate, vitamin D, fibroblast growth factor, and klotho, as well as abnormal bone mineralization, remodeling, and turnover. In addition, we explore the diagnostic tools and possible therapeutic approaches for the management and prevention of CKD-associated osteoporosis. Patients with CKD show higher osteoporosis prevalence, greater fracture rate, increased morbidity and mortality, and an elevated occurrence of hip fracture. We also rule out that increased severity of CKD is related to a more severe condition of osteoporosis. Furthermore, supplements such as calcium and vitamin D as well as lifestyle modifications such as exercise and cessation of smoking and alcohol help in fracture prevention. However, new approaches and advancements in treatment are needed to reduce the fracture risk in patients with CKD. Therefore, further collaborative multidisciplinary research is needed in this regard.
PubMed: 34692259
DOI: 10.7759/cureus.18488 -
The American Journal of Clinical... Feb 2022Circulating 25-hydroxyvitamin D [25(OH)D] has been the accepted vitamin D exposure/intake biomarker of choice within recent DRI exercises, but use of other vitamin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating 25-hydroxyvitamin D [25(OH)D] has been the accepted vitamin D exposure/intake biomarker of choice within recent DRI exercises, but use of other vitamin D-related biomarkers as well as functional markers has been suggested. These may be of value in future vitamin D DRI exercises, such as the FAO/WHO's one for young children.
OBJECTIVES
To systematically review the usefulness of circulating 25(OH)D, parathyroid hormone (PTH), free and bioavailable 25(OH)D, C3-epimer of 25(OH)D, vitamin D3, 24,25-dihydroxyvitamin D [24,25(OH)2D], and bone turnover markers and calcium absorption as vitamin D biomarkers for DRI development in children.
METHODS
Methods included structured searches of published articles, full-text reviews, data extraction, quality assessment, meta-analysis, and random-effects meta-regression.
RESULTS
Fifty-nine vitamin D supplementation randomized controlled trials (RCTs) were included (39 in infants/children as the priority group and the remainder in adults since pediatric studies were absent/limited). Vitamin D supplementation significantly raised circulating 25(OH)D in infants and children, but the response was highly heterogeneous [weighted mean difference (WMD): 27.7 nmol/L; 95% CI: 22.9, 32.5; 27 RCTs; I2 = 93%]. Meta-regression suggested an increase by 1.7 nmol/L (95% CI: 0.7, 2.6) in serum 25(OH)D per each 100-IU increment in vitamin D intake (P = 0.0005). Vitamin D supplementation had a significant effect on circulating 24,25(OH)2D (WMD: 3.4 nmol/L; 95% CI: 2.4, 4.5; 13 RCTs; I2 = 95%), with a dose-response relation (+0.15 nmol/L per 100 IU; 95% CI: -0.01, 0.29). With circulating PTH, although there was a significant effect of vitamin D on WMD (P = 0.05), there was no significant dose-response relation (P = 0.32). Pediatric data were too limited in relation to the usefulness of the other biomarkers.
CONCLUSIONS
Circulating 25(OH)D may be a useful biomarker of vitamin D exposure/intake for DRI development in infants and children. Circulating 24,25(OH)2D also showed some promise, but further data are needed, especially in infants and children.
Topics: Biomarkers; Bone Remodeling; Calcium, Dietary; Child; Child, Preschool; Dietary Supplements; Female; Humans; Infant; Male; Nutritional Status; Parathyroid Hormone; Randomized Controlled Trials as Topic; Recommended Dietary Allowances; Vitamin D; Vitamin D Deficiency
PubMed: 34687199
DOI: 10.1093/ajcn/nqab357 -
Nutrients Sep 2021Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D) or cholecalciferol (vitamin D), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D) and cholecalciferol (vitamin D) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density.
METHODS
Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to "Preferred Reporting Items for Systematic reviews and Meta-analysis" guidelines. Search terms were constructed on the basis of the "participants", "intervention", "control", "outcome" and "study type" (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods.
RESULTS
Apparently healthy human participants ( = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis.
CONCLUSIONS
Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation.
Topics: Cholecalciferol; Ergocalciferols; Humans; Multivariate Analysis; Parathyroid Hormone; Publication Bias; Regression Analysis; Risk
PubMed: 34684328
DOI: 10.3390/nu13103328 -
Revista Brasileira de Ginecologia E... Sep 2021To evaluate the effects of vitamin D supplementation in the postpartum period of women with previous gestational diabetes mellitus (GDM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effects of vitamin D supplementation in the postpartum period of women with previous gestational diabetes mellitus (GDM).
METHODS
Randomized clinical trials of pregnant women with GDM of any chronological, gestational age and parity, with no history of previous disease who received vitamin D supplementation in the prenatal and/or postpartum period and were evaluated in the postpartum period were included. The PubMed, EMBASE, Cochrane, and LILACS databases were consulted until July 2019. Serum vitamin D concentration (25-hydroxyvitamin D in nmol/L), fasting blood glucose, glycated hemoglobin, serum calcium concentration, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), parathyroid hormone (PTH) and body mass index (BMI) were evaluated. Similar results in at least two trials were plotted using the RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. The quality of the evidence was generated according to the classification, development, and evaluation of the classification of the recommendations.
RESULTS
Four studies were included in the present review (200 women). The findings indicate that there is no difference in the postpartum period in women diagnosed with previous GDM who received vitamin D supplementation in the prenatal and/or in the postpartum period, showing only that there was a significant increase in the concentration of vitamin D (relative risk [RR]: 1.85; 95% confidence interval [CI]: 1.02-2.68).
CONCLUSION
This increase in the concentration of vitamin D should be interpreted with caution, since the assessment of the quality of the evidence was very low. For the other analyzed outcomes, there was no significance between the intervention and control groups, and the outcomes, when analyzed in their strength of evidence, were considered very low and low in their evaluation.
Topics: Diabetes, Gestational; Dietary Supplements; Female; Humans; Pregnancy; Randomized Controlled Trials as Topic; Vitamin D; Vitamins
PubMed: 34670305
DOI: 10.1055/s-0041-1734000