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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 -
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 -
Nutrition (Burbank, Los Angeles County,... Dec 2023Menopause and vitamin D deficiency increase bone reabsorption and bone fracture risk in women in postmenopause, and vitamin D supplementation may improve bone health and... (Review)
Review
Supplementation of vitamin D isolated or calcium-associated with bone remodeling and fracture risk in postmenopausal women without osteoporosis: A systematic review of randomized clinical trials.
Menopause and vitamin D deficiency increase bone reabsorption and bone fracture risk in women in postmenopause, and vitamin D supplementation may improve bone health and decrease bone fracture risk. This study aims to discuss the effect of vitamin D supplementation, isolated or calcium-associated, on remodeling and fracture risk bone in women in postmenopause without osteoporosis. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO database registration: CRD42022359796). A search was conducted in four databases and gray literature using MeSH and similar terms related to supplements, vitamin D, calcium, remodeling, and fracture bone, without the restriction of language and year of publication. A total of 3460 studies were identified, and nine were selected. Vitamin D supplementation increased 25-hydroxyvitamin D levels ≥10 ng/mL and decreased parathyroid hormone secretion dependent on baseline levels. The doses of 400 IU of vitamin D improved the percentage of carboxylated osteocalcin, whereas 800 to 1000 IU combined with calcium resulted in reduced, improved, or maintained bone mineral density and reduced alkaline phosphatase levels. However, 4000 IU alone or combined with calcium for 6 mo did not improve C-telopeptide and procollagen type 1 peptide levels. Additionally, 15 000 IU/wk increased the cortical area of metacarpal bone, whereas 500 000 IU of vitamin D annually for 5 y did not contribute to reducing the fracture risk and falls. Only one study found a reduction in fracture risk (dose of 800 IU of vitamin D plus 1200 mg of calcium). Thus, the vitamin D supplementation, alone or calcium-associated, improved the status of 25-hydroxyvitamin D and bone remodeling, but it was not possible to assert that it reduced fracture bone risk in postmenopausal women.
Topics: Humans; Female; Calcium; Postmenopause; Randomized Controlled Trials as Topic; Vitamin D; Vitamins; Osteoporosis; Fractures, Bone; Calcium, Dietary; Calcifediol; Dietary Supplements; Bone Remodeling
PubMed: 37544189
DOI: 10.1016/j.nut.2023.112151 -
Cardiovascular Journal of Africa Jul 2023In dialysis patients, vascular calcification is a common complication and is closely related to the morbidity and mortality of cardiovascular disease. We performed a... (Review)
Review
BACKGROUND
In dialysis patients, vascular calcification is a common complication and is closely related to the morbidity and mortality of cardiovascular disease. We performed a systematic review to determine the efficacy and safety of sodium thiosulfate (STS) in the progression of vascular calcification in dialysis patients with end-stage renal disease.
METHODS
The PubMed, Web of Science, Embase, Cochrane Library, Wanfang, CNKI, China Biology Medicine disc and Weipu databases were searched up to 9 March 2022 for clinical trials to synthesise findings on the efficacy and safety of STS in the progression of vascular calcification in dialysis patients. The primary outcome was coronary artery calcification scores (CACS) or abdominal aortic calcification scores (AACS) or Kauppila index. The secondary outcome was pulse-wave velocity (PWV). Laboratory data were shown in safety data. A random-effect model was used to provide the summary measures of effect [standardised mean difference (SMD) and 95% confidence interval (CI)].
RESULTS
Seven randomised, controlled trials and one nonrandomised, controlled trial involving 370 patients were included. Six studies reported that the progression of CACS or AACS was slower in the intravenous STS group compared with the control group (SMD -3.24, 95% CI: -5.29, -1.18, = 0.002). Two studies showed the increase in PWV was less in the STS group compared with the control group (SMD -0.52, 95% CI: -0.92, -0.13, = 0.009). During the trial period, a lower high-sensitivity C-reactive protein level (SMD 1.61, 95% CI: 0.19, 3.04, = 0.03), a decrease in serum bicarbonate level (SMD 0.67, 95% CI: 0.22, 1.11, = 0.003) and an increase in serum phosphate level (SMD -0.32, 95% CI: -0.62, -0.03, = 0.03) were noted in the intravenous STS group compared with the control group. However, serum calcium and parathyroid hormone levels showed no difference between the two groups after the trials. The most common adverse events were temporary nausea and vomiting, which occurred in 12.5 to 75% of patients.
CONCLUSIONS
Intravenous STS may slow down the progression of vascular calcification and ameliorate arterial stiffness in dialysis patients. Reliably defining the efficacy and safety of intravenous STS in attenuating the progression of vascular calcification requires a high-quality trial with a large sample size.
PubMed: 37526956
DOI: 10.5830/CVJA-2023-020 -
World Neurosurgery Nov 2023Our goal was to assess teriparatide's (TP) effectiveness in improving radiographic and functional outcomes after spinal fusion surgery. This meta-analysis included... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Our goal was to assess teriparatide's (TP) effectiveness in improving radiographic and functional outcomes after spinal fusion surgery. This meta-analysis included randomized controlled trials (RCTs) and comparative cohort studies. The findings provide valuable insights and guidance for surgeons treating osteoporotic patients undergoing spinal fusion surgery.
METHODS
We conducted a systematic review to assess TP's efficacy in spinal fusion surgery for osteoporosis. Through thorough selection, data extraction, and quality assessment, we employed network meta-analysis to evaluate radiographic outcomes (fusion rate, screw loosening, vertebral fracture) and changes in bone mineral density measured by Hounsfield units. Functional outcomes were assessed using the Oswestry Disability Index scales. Our study aims to comprehensively understand TP's impact and effectiveness in spinal fusion surgery.
RESULTS
A total of 868 patients were included in the analysis. All patients underwent thoracolumbar internal fixation fusion surgery and were divided into following 2 groups: the TP treatment group and the control group. The results revealed significant differences in radiological outcomes. The fusion rate showed a significant difference, as well as screw loosening, and bone mineral density measured in Hounsfield units. However, there was no significant difference in vertebral fracture. The TP group demonstrated favorable effects with statistical significance. In terms of functional outcomes, there was no significant difference in the assessment of Oswestry Disability Index scores between the 2 treatment groups.
CONCLUSIONS
The meta-analysis demonstrated that the TP group exhibited significantly better outcomes, particularly in radiological measures, when compared to the control group. The use of TP in spinal fusion surgery shows promise in reducing postoperative complications and providing overall benefits.
Topics: Humans; Teriparatide; Spinal Fractures; Spinal Fusion; Osteoporosis; Bone Density Conservation Agents; Lumbar Vertebrae; Treatment Outcome
PubMed: 37479030
DOI: 10.1016/j.wneu.2023.07.056 -
Diabetes & Metabolic Syndrome Aug 2023Studies have suggested that high parathyroid hormone (PTH) was associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH),... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Studies have suggested that high parathyroid hormone (PTH) was associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), although the results from existing studies are inconsistent. Using systematic review and meta-analysis, we aimed to determine the association of PTH with NAFLD and NASH.
METHODS
Potentially eligible studies were identified from Embase and Medline databases from using search strategy consisting of terms for "NAFLD/NASH", and "PTH". Eligible study must consist of one group of patients with NAFLD/NASH and another group without NAFLD/NASH. The study must provide mean ± SD PTH in both groups. We extracted such data to calculate mean difference (MD). Pooled MD was then calculated by combining MDs of each study using random-effects model. Funnel plot was used to assess for the presence of publication bias.
RESULTS
A total of 388 articles were identified. After systematic review, 12 studies fulfilled the eligibility criteria and were included into the meta-analysis. The meta-analysis of 10 studies revealed the significant association between high PTH and NAFLD, with the pooled MD of 5.479 (95%CI 0.947-10.011, I 82.4%). The funnel plot was symmetric and did not suggest publication bias. The meta-analysis of 4 studies revealed the non-significant association between high PTH and NASH, with the pooled MD of 11.955 (95%CI -4.703 - 28.614, I 81.0%).
CONCLUSIONS
High PTH level is significantly associated with NAFLD and can be used as a marker of NAFLD. However, high PTH level is non-significantly associated with NASH. Further studies are needed to increase the sample size and eliminate the confounding factors.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Parathyroid Hormone
PubMed: 37451113
DOI: 10.1016/j.dsx.2023.102827 -
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 -
American Journal of Kidney Diseases :... Nov 2023Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality,...
RATIONALE & OBJECTIVE
Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD.
STUDY DESIGN
Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023.
SETTING & STUDY POPULATIONS
Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded.
SELECTION CRITERIA FOR STUDIES
RCTs with≥3 months of follow-up evaluating a vitamin D compound.
DATA EXTRACTION
Data were extracted independently by three investigators.
ANALYTICAL APPROACH
Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE.
RESULTS
Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium.
LIMITATIONS
Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality.
CONCLUSIONS
Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture and cardiovascular and kidney outcomes were uncertain.
TRIAL REGISTRATION
Registered at PROSPERO with study number CRD42017057691.
PLAIN-LANGUAGE SUMMARY
Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.
PubMed: 37356648
DOI: 10.1053/j.ajkd.2023.04.003 -
Hemodialysis International.... Oct 2023The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a systematic review and meta-analysis of observational studies.
METHODS
The MEDLINE, EMBASE, and Cochrane Library databases were searched in June 2022 to identify studies that evaluated the risk of denosumab-associated hypocalcemia and changes in bone metabolism, changes in BMD from baseline to post-treatment in patients with ESRD.
FINDINGS
Twelve studies with 348 participants were included. The pooled incidence of hypocalcemia during denosumab treatment was 35.0% (95% confidence interval [CI], 25%-46%; I = 63.6%). There were no significant changes in either the serum calcium or phosphate levels from the baseline to post-treatment period; the mean differences were 0.04 mg/dL (95% CI, -0.12 to 0.20 mg/dL) and -0.39 mg/dL (95% CI, -0.89 to 0.12 mg/dL). We found significant changes in the alkaline phosphatase and parathyroid hormone levels; the standardized mean differences were -2.98 (95% CI, -5.36 to -0.59) and -3.12 (95% CI: -4.94 to -1.29), respectively. Denosumab may increase BMD, with mean differences of 9.10% (95% CI: 4.07%-14.13%) and 9.00% (95% CI: 5.93%-12.07%) for the femoral neck and lumbar spine, respectively.
DISCUSSION
Denosumab increased the BMDs of the lumbar spine and femoral neck in patients with ESRD. The onset of hypocalcemia must be carefully monitored during denosumab administration.
Topics: Humans; Bone Density; Denosumab; Hypocalcemia; Bone Density Conservation Agents; Renal Dialysis; Kidney Failure, Chronic
PubMed: 37264758
DOI: 10.1111/hdi.13098 -
The Journal of Clinical Endocrinology... Oct 2023Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid... (Meta-Analysis)
Meta-Analysis
CONTEXT
Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia.
OBJECTIVE
The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD).
METHODS
A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting.
RESULTS
Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed.
CONCLUSION
This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.
Topics: Humans; Calcifediol; Calcium; Ergocalciferols; Hyperparathyroidism, Secondary; Network Meta-Analysis; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic
PubMed: 37235771
DOI: 10.1210/clinem/dgad289