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International Urology and Nephrology May 2024Mineral and bone disease in children with chronic kidney disease can cause abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D and when left... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mineral and bone disease in children with chronic kidney disease can cause abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D and when left untreated can result in impaired growth, bone deformities, fractures, and vascular calcification. Cinacalcet is a calcimimetic widely used as a therapy to reduce parathyroid hormone levels in the adult population, with hypocalcemia among its side effects. The analysis of safety in the pediatric population is questioned due to the scarcity of randomized clinical trials in this group.
OBJECTIVE
To assess the onset of symptomatic hypocalcemia or other adverse events (serious or non-serious) with the use of cinacalcet in children and adolescents with mineral and bone disorder in chronic kidney disease.
DATA SOURCES AND STUDY ELIGIBILITY CRITERIA
The bibliographic search identified 2699 references from 1927 to August/2023 (57 LILACS, 44 Web of Science, 686 PubMed, 131 Cochrane, 1246 Scopus, 535 Embase). Four references were added from the bibliography of articles found and 12 references from the gray literature (Clinical Trials). Of the 77 studies analyzed in full, 68 were excluded because they did not meet the following criteria: population, types of studies, medication, publication types and 1 article that did not present results (gray literature).
PARTICIPANTS AND INTERVENTIONS
There were 149 patients aged 0-18 years old with Chronic Kidney Disease and mineral bone disorder who received cinacalcet.
STUDY APPRAISAL AND SYNTHESIS METHODS
Nine eligible studies were examined for study type, size, intervention, and reported outcomes.
RESULTS
There was an incidence of 0.2% of fatal adverse events and 16% of serious adverse events (p < 0.01 and I = 69%), in addition to 10.7% of hypocalcemia, totaling 45.7% of total adverse events.
LIMITATIONS
There was a bias in demographic information and clinical characteristics of patients in about 50% of the studies and the majority of the studies were case series.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
If used in the pediatric population, the calcimimetic cinacalcet should be carefully monitored for serum calcium levels and attention to possible adverse events, especially in children under 50 months.
SYSTEMATIC REVIEW REGISTRATION NUMBER (PROSPERO REGISTER)
CRD42019132809.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Bone Diseases; Calcimimetic Agents; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Cinacalcet; Hyperparathyroidism, Secondary; Hypocalcemia; Minerals; Parathyroid Hormone; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 37964112
DOI: 10.1007/s11255-023-03844-2 -
Frontiers in Physiology 2023In vertebrates fibroblast growth factor 23 (FGF23) is a phosphate regulating hormone closely linked to calcium regulation by vitamin D and parathyroid hormone (PTH)....
In vertebrates fibroblast growth factor 23 (FGF23) is a phosphate regulating hormone closely linked to calcium regulation by vitamin D and parathyroid hormone (PTH). Although phosphorus, calcium and vitamin D are important for poultry well-being, relatively little is known about their levels of FGF23. Our objective was to quantitatively estimate the blood FGF23 level in birds, and to examine its relationship to diet and blood levels of other components of phosphate and calcium homeostasis. A systematic search of Agricola, Embase and Medline identified 86 studies focused on FGF23 in birds, from which 12 manuscripts reporting data for 60 independent groups of chickens were included in the analysis. FGF23 levels were 256 pg/ml (Confidence interval (CI): 215, 297) in broilers (39 datasets containing 435 birds), and 256 pg/ml (CI: 178, 339) in egg-laying hens (21 datasets containing 208 birds). FGF23 levels did not correlate with dietary phosphorus, calcium or vitamin D, or with plasma calcium or PTH. FGF23 levels demonstrated a trend to positively correlate with plasma phosphate and a strongly and positive correlation with plasma vitamin D. This study provides normative estimates of FGF23 levels in poultry birds and new insights into the regulation of calcium and phosphate homeostasis.
PubMed: 37908340
DOI: 10.3389/fphys.2023.1279204 -
Orthopedic Research and Reviews 2023Teriparatide is a recombinant human parathyroid hormone analog with anabolic mechanism of action utilized in the treatment of osteoporosis with well-established clinical... (Review)
Review
Teriparatide is a recombinant human parathyroid hormone analog with anabolic mechanism of action utilized in the treatment of osteoporosis with well-established clinical efficacy. Its use is significantly hindered due to label warnings resulting from pre-clinical rat studies demonstrating an increased risk of osteosarcoma. However, clinical trials and post-marketing surveillance studies did not demonstrate any increased risk of osteosarcoma, even after prolonged periods of surveillance reaching up to 15 years, with most of the identified cases of osteosarcomas being solitary and predominantly attributed to other factors. This systematic review provides a comprehensive overview of the currently available literature and provides the highest level of clinical evidence towards demonstrating the lack of any substantial evidence towards osteosarcoma development in patients utilizing TPTD.
PubMed: 37791038
DOI: 10.2147/ORR.S408718 -
The Journal of Clinical Endocrinology... Feb 2024The optimal management of pregnancy and lactation-associated osteoporosis (PLO) has not been designated. (Meta-Analysis)
Meta-Analysis
CONTEXT
The optimal management of pregnancy and lactation-associated osteoporosis (PLO) has not been designated.
OBJECTIVE
To systematically review the best available evidence regarding the effect of different therapeutic interventions on bone mineral density (BMD) and risk of fractures in these patients.
METHODS
A comprehensive search was conducted in PubMed/Scopus databases until December 20, 2022. Data were expressed as weighted mean difference (WMD) with 95% CI. The I2 index was employed for heterogeneity. Studies conducted in women with PLO who received any antiosteoporosis therapy were included. Studies including women with secondary causes of osteoporosis or with transient osteoporosis of the hip were excluded. Data extraction was independently completed by 2 researchers.
RESULTS
Sixty-six studies were included in the qualitative analysis (n = 451 [follow-up time range 6-264 months; age range 19-42 years]). The increase in lumbar spine (LS) BMD with calcium/vitamin D (CaD), bisphosphonates, and teriparatide was 2.0% to 7.5%, 5.0% to 41.5%, and 8.0% to 24.4% at 12 months, and 11.0% to 12.2%, 10.2% to 171.9%, and 24.1% to 32.9% at 24 months, respectively. Femoral neck (FN) BMD increased by 6.1% with CaD, and by 0.7% to 18% and 8.4% to 18.6% with bisphosphonates and teriparatide (18-24 months), respectively. Meta-analysis was performed for 2 interventional studies only. Teriparatide induced a greater increase in LS and FN BMD than CaD (WMD 11.5%, 95% CI 4.9-18.0%, I2 50.9%, and 5.4%, 95% CI 1.2-9.6%, I2 8.1%, respectively).
CONCLUSION
Due to high heterogeneity and lack of robust comparative data, no safe conclusions can be made regarding the optimal therapeutic intervention in women with PLO.
Topics: Pregnancy; Humans; Female; Young Adult; Adult; Teriparatide; Osteoporosis; Bone Density; Bone Density Conservation Agents; Diphosphonates; Lactation
PubMed: 37708365
DOI: 10.1210/clinem/dgad548 -
International Journal of Surgery... Dec 2023
Meta-Analysis
A commentary on 'The role of rapid intraoperative parathyroid hormone (ioPTH) assay in determining outcome of parathyroidectomy in primary hyperparathyroidism: A systematic review and meta-analysis'.
Topics: Humans; Parathyroid Hormone; Parathyroidectomy; Hyperparathyroidism, Primary; Monitoring, Intraoperative; Retrospective Studies
PubMed: 37702567
DOI: 10.1097/JS9.0000000000000716 -
Frontiers in Endocrinology 2023Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal levels of parathyroid hormone. The...
Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal levels of parathyroid hormone. The disease is caused by a heterozygous activating mutation of the calcium-sensing receptor () gene, encoding a G-Protein-coupled cell membrane sensor of extracellular calcium concentration mainly expressed by parathyroid glands, renal tubules, and the brain. ADH1 has been linked to 113 unique germline mutations, of which nearly 96% are missense mutations. There is often a lack of a clear genotype/phenotype correlation in the reported literature. Here, we described a case series of 6 unrelated ADH1 probands, each one bearing a gain-of-function mutation, and two children of one of these cases, matching our identified mutations to the same ones previously reported in the literature, and comparing the clinical and biochemical characteristics, as well as the complication profile. As a result of these genetic and clinical comparisons, we propose that a genotype/phenotype correlation may exist because our cases showed similar presentation, characteristics, and severity, with respect to published cases with the same or similar mutations. We also contend that the severity of the presentation is highly influenced by the specific variant. These findings, however, require further evaluation and assessment with a systematic review.
Topics: Gain of Function Mutation; Receptors, Calcium-Sensing; Calcium; Research; Mutation
PubMed: 37654565
DOI: 10.3389/fendo.2023.1215036 -
Plants (Basel, Switzerland) May 2023Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific... (Review)
Review
Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoprotegerin, osterix, RANKL, Runx2); and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/β, Notch, BMP, SMAD). Some phytochemical compounds-such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others-presented a beneficial and stimulating effect in the bone regeneration process due to the pro-estrogenic activity, the antioxidant and the anti-inflammatory effect and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone-related pathologies envisaged through the incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.
PubMed: 37653972
DOI: 10.3390/plants12102055 -
Obesity Facts 2023Managing nutritional deficiencies is an essential component in the treatment of severe obesity. Vitamin D deficiency is often reported in investigations in severely... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Managing nutritional deficiencies is an essential component in the treatment of severe obesity. Vitamin D deficiency is often reported in investigations in severely obese cohorts. However, no prior study has summarized findings on this topic. Consequently, the aim of this systematic review and meta-analysis was to investigate the 25-hydroxyvitamin D [25(OH)D] status in individuals with severe obesity in different regions worldwide. We also evaluated levels of calcium, parathyroid hormone (PTH), and magnesium as secondary outcome measures.
METHODS
We searched Medline, PubMed, Scopus, the Cochrane Library, and EMBASE for relevant observational studies published in English from 2009 to October 2021. The heterogeneity index among the studies was determined using the Cochran (Q) and I2 tests. Based on the heterogeneity results, the random-effect model was applied to estimate the prevalence of vitamin D deficiency.
RESULTS
We identified 109 eligible observational studies. Overall, 59.44% of patients had vitamin D deficiency [25(OH)D <20 ng/mL], whereas 26.95% had vitamin D insufficiency [25(OH)D 20-30 ng/mL]. Moreover, the mean 25(OH)D level was 18.65 ng/mL in 96 studies. The pooled mean estimate of the serum calcium, PTH, and magnesium was 9.26 mg/dL (95% confidence interval [CI]: 9.19-9.32, I2 = 99.7%, p < 0.001), 59.24 pg/mL (95% CI: 54.98, 63.51, I2 = 99.7%, p < 0.001), and 0.91 mg/dL (95% CI: 0.84, 0.98, I2 = 100.0%, p < 0.001), respectively. The results of the subgroup analysis indicated that the mean estimates of 25(OH)D were highest in North America (21.71 ng/mL [19.69, 23.74], [I2 = 97.2%, p < 0.001]) and lowest in Southeast Asia (14.93 ng/mL [14.54, 15.33], [I2 = 0.0%, p = 0.778]).
CONCLUSION
The results obtained showed a significant prevalence of vitamin D deficiency among severely obese individuals in various geographical regions, whereas the highest and lowest mean estimates were reported for North America and Southeast Asia, respectively.
Topics: Humans; Obesity, Morbid; Calcium; Magnesium; Vitamin D; Vitamin D Deficiency; Obesity; Parathyroid Hormone
PubMed: 37640022
DOI: 10.1159/000533828 -
Frontiers in Pharmacology 2023The efficacy of cuttlebone for treating hyperphosphatemia in patients with end-stage renal disease and its safety remained unclear. Randomized controlled trials...
The efficacy of cuttlebone for treating hyperphosphatemia in patients with end-stage renal disease and its safety remained unclear. Randomized controlled trials comparing the efficacy of cuttlebone with conventional interventions were retrieved from MEDLINE, EMBASE, Cochrane Library, Airiti Library, and other major Chinese databases until 1 February 2023. The primary outcome was circulating phosphate concentration, while secondary outcomes included circulating calcium and intact parathyroid hormone levels, calcium-phosphorus product, and treatment-related side-effects. Analysis of nine studies published between 2000 and 2019 including 726 participants showed a lower circulating phosphate concentration in the cuttlebone group than in controls [mean difference (MD) = -0.23, 95% CI: -0.39 to -0.06, = 0.006, I = 94%, 726 patients] and a dose-dependent effect of cuttlebone against hyperphosphatemia. Therapeutic benefits were noted after both short-term (1-2 months) and long-term (3-6 months) treatments. Besides, patients receiving hemodialysis showed a better response to cuttlebone than those receiving peritoneal dialysis. There was no difference in circulating calcium level (mean difference = 0.03, 95% CI: -0.01 to 0.07, = 0.17, I = 34%, 654 patients), while patients receiving cuttlebone showed lower circulating iPTH level and calcium-phosphorus product (MD = -43.63, 95% CI: -74.1 to -13.16, = 0.005, I = 76%, 654 patients), (MD = -0.38, 95% CI: -0.38 to -0.01, = 0.04, I = 83%, 520 patients). No difference in the risks of constipation, gastrointestinal discomfort, and elevated blood calcium was noted between the two groups. Compared with conventional phosphate-binding agents, cuttlebone more efficiently suppressed hyperphosphatemia with a dose-dependent effect. The limited number of included studies warrants further clinical investigations to verify our findings. https://www.crd.york.ac.uk/prospero/, identifier CRD42023396300.
PubMed: 37554990
DOI: 10.3389/fphar.2023.1206366 -
Nutrients Jul 2023Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host... (Review)
Review
Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host immunity. Vitamin D deficiency is common in patients with end-stage kidney disease (ESKD); however, current clinical practice has favored the use of the active hormone. Whether vitamin D deficiency should be corrected in patients with ESKD remains unclear, as few randomized trials have been conducted. In this systematic review, we summarize the current evidence examining whether vitamin D supplementation improves outcomes, beyond mineral metabolism, in patients with ESKD. Data from randomized controlled trials of adults with ESKD were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection from inception to February 2023. Twenty-three trials composed of 2489 participants were identified for inclusion. Data were synthesized by two independent reviewers and summarized in tables organized by outcome. Outcomes included measures of mortality, cardiovascular disease, inflammation, muscle strength/function, nutrition, patient well-being, and outcomes specific to ESKD including erythropoietin usage, pruritus, and dialysis access maturation. The Cochrane risk of Bias Tool (RoB 2, 2019) was used to assess study quality. Overall, our findings indicate a minimal and varied benefit of native vitamin D supplementation. From the largest studies included, we determine that vitamin D has no demonstrated effect on patient-reported measures of well-being or utilization of erythropoietin, nor does it change levels of the inflammation biomarker -reactive protein. Included trials were heterogeneous with regards to outcomes, and the majority studied small participant populations with a relatively short follow-up. We conclude that vitamin D supplementation corrects vitamin D deficiency and is safe and well-tolerated in humans with ESKD. However, it is not clear from clinical trials conducted to date that a causal pathway exists between 25(OH)D and pleiotropic effects that is responsive to vitamin D treatment.
Topics: Adult; Humans; Vitamin D; Cardiovascular Diseases; Renal Dialysis; Randomized Controlled Trials as Topic; Vitamins; Kidney Failure, Chronic; Vitamin D Deficiency; Dietary Supplements; Erythropoietin; Minerals
PubMed: 37447398
DOI: 10.3390/nu15133072