Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Background: Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Patients and methods: Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. Results: A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. Conclusions: The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

Intravenous ferric derisomaltose versus saccharated ferric oxide for iron deficiency anemia associated with menorrhagia: a randomized, open-label, active-controlled, noninferiority study.

A multicenter, randomized, open-label, phase III study was conducted to compare the efficacy and safety of intravenous ferric derisomaltose (FDI) versus saccharated ferric oxide (SFO) in Japanese patients with iron deficiency anemia associated with menorrhagia. FDI can be administered as a single dose up to 1000 mg, whereas SFO has a maximum single dose of 120 mg. The primary endpoint, which was the maximum change in hemoglobin concentration from baseline, was noninferior for the FDI group compared with the SFO group. The incidence of treatment-emergent adverse events was lower in the FDI group (66.2%) than in the SFO group (90.8%). Notably, the incidence of serum phosphorus level < 2.0 mg/dL was significantly lower in the FDI group (8.4%) than in the SFO group (83.2%), and severe hypophosphatemia (≤ 1.0 mg/dL) occurred in 6.7% of SFO­treated patients compared with none in the FDI group. The percentage of patients who achieved the cumulative total iron dose during the 8-week treatment period was higher in the FDI group (92.8%) than in the SFO group (43.2%). The study met its primary endpoint, and also demonstrated the tolerability of a high dose of FDI per infusion, with a lower incidence of hypophosphatemia.

Studying the Effects of Cold Plasma Phosphorus Using Physiological and Digital Image Processing Techniques.

The goal of this study is to see how cold plasma affects rabbit bone tissue infected with osteoporosis. The search is divided into three categories: control, infected, and treated. The rabbits were subjected to cold plasma for five minutes in a room with a microwave plasma voltage of "175 V" and a gas flow of "2." A histopathological photograph of infected bone cells is obtained to demonstrate the influence of plasma on infected bone cells, as well as the extent of destruction and effect of plasma therapy before and after exposure. The findings of the search show that plasma has a clear impact on Ca and vitamin D levels. In the cold plasma, the levels of osteocalcin and alkali phosphates (ALP) respond as well. Image processing techniques (second-order gray level matrix) with textural elements are employed as an extra proof. The outcome gives good treatment indicators, and the image processing result corresponds to the biological result.

Icariin attenuates thioacetamide­induced bone loss via the RANKL­p38/ERK­NFAT signaling pathway.

There is an increasing incidence of destructive bone disease caused by osteoclast proliferation. This is characterized by reduced bone mass and imbalance of bone homeostasis. Icariin (ICA), a flavonoid compound isolated from Epimedium, has anti­osteoporosis activity and inhibits the formation of osteoclasts and bone resorption. The purpose of the present study was to investigate the protective effect of ICA on osteoclastic differentiation induced by thioacetamide (TAA) and its possible mechanism in Sprague Dawley (SD) rats. In the present study, SD rats were intraperitoneally injected with TAA (300 mg/kg) for the bone loss model, treated with ICA (600 mg/kg, intragastric gavage) in the ICA group and TAA+ICA group for treatment of bone loss for 6 weeks. Indexes associated with bone metabolism, such as alkaline phosphatase, N­terminal telopeptide of type­I collagen (NTX­I), calcium (Ca), phosphorus (P) and magnesium (Mg) in the serum, were detected. Osteoclast differentiation of femoral tissues was detected by hematoxylin and eosin and tartrate­resistant acid phosphatase staining. The femoral bone mass was evaluated using a three­point bending test and micro computed tomography. Western blotting was used to detect the expression levels of osteoclast­related proteins in each group. In the rats treated with TAA, the serum concentrations of Ca, P and Mg were decreased, the serum concentration of NTX­I was increased, osteoclast differentiation of the femur was increased, femur bone stress and bone mass were decreased and the bone loss and osteoclast formation were reduced after ICA treatment. In addition, ICA inhibited the protein expression of receptor activator of nuclear factor κ­Β ligand (RANKL), receptor activator of nuclear factor κ­B (RANK), p38, ERK, c­Fos and nuclear factor of activated T cells 1 (NFATc1) in the femur of rats treated with TAA. The results suggested that ICA may inhibit osteoclast differentiation by downregulating the RANKL­p38/ERK­NFAT signaling pathway and prevent TAA­induced bone loss. The results are helpful to understand the mechanism of osteoclast differentiation induced by TAA, as well as the antiresorptive activity and molecular mechanism of ICA, and to provide new ideas for the treatment of osteolytic diseases.

The value of clinical-ultrasonographic feature model to predict the severity of secondary hyperparathyroidism.

OBJECTIVES: To analyze conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in patients with secondary hyperparathyroidism (SHPT) and to evaluate the clinical-ultrasonographic feature based model for predicting the severity of SHPT. METHODS: From February 2016 to March 2021, a total of 59 patients (age 51.3 ± 11.7 years, seCr 797.8 ± 431.7 µmol/L, iPTH 1535.1 ± 1063.9 ng/L) with SHPT (including 181 parathyroid glands (PTGs)) without the history of intact parathyroid hormone (iPTH)-reducing drugs using were enrolled. The patients were divided into the mild SHPT group (mSHPT, iPTH <800 ng/L) and the severe SHPT group (sSHPT, iPTH ≥ 800 ng/L) according to the serum iPTH level. The clinical test data of patients were collected and CUS and CEUS examinations were performed for every patient. Multivariable logistic regression model according to clinical-ultrasonographic features was adopted to establish a nomogram. We performed K-fold cross-validation on this nomogram model and nomogram performance was determined by its discrimination, calibration, and clinical usefulness. RESULTS: There were 19 patients in the mSHPT group and 40 patients in the sSHPT group. Multivariable logistic regression indicated serum calcium, serum phosphorus and total volume of PTGs were independent predictors related with serum iPTH level. Even though CEUS score of wash-in and wash-out were showed related to severity of SHPT in univariate logistic regression analysis, they were not predictors of SHPT severity (p = 0.539, 0.474 respectively). The nomogram developed by clinical and ultrasonographic features showed good calibration and discrimination. The accuracy and the area under the curve (AUC), positive predictive value (PPV), negative predictive value (NPV) and accuracy of this model were 0.888, 92.5%, 63.2% and 83.1%, respectively. When applied to internal validation, the score revealed good discrimination with stratified fivefold cross-validation in the cohort (mean AUC = 0.833). CONCLUSIONS: The clinical-ultrasonographic features model has good performance for predicting the severity of SHPT.

Estimated Glomerular Filtration Rate in Chronic Kidney Disease: A Critical Review of Estimate-Based Predictions of Individual Outcomes in Kidney Disease.

Chronic kidney disease (CKD) is generally regarded as a final common pathway of several renal diseases, often leading to end-stage kidney disease (ESKD) and a need for renal replacement therapy. Estimated GFR (eGFR) has been used to predict this outcome recognizing its robust association with renal disease progression and the eventual need for dialysis in large, mainly cross-sectional epidemiological studies. However, GFR is implicitly limited as follows: (1) GFR reflects only one of the many physiological functions of the kidney; (2) it is dependent on several non-renal factors; (3) it has intrinsic variability that is a function of dietary intake, fluid and cardiovascular status, and blood pressure especially with impaired autoregulation or medication use; (4) it has been shown to change with age with a unique non-linear pattern; and (5) eGFR may not correlate with GFR in certain conditions and disease states. Yet, many clinicians, especially our non-nephrologist colleagues, tend to regard eGFR obtained from a simple laboratory test as both a valid reflection of renal function and a reliable diagnostic tool in establishing the diagnosis of CKD. What is the validity of these beliefs? This review will critically reassess the limitations of such single-focused attention, with a particular focus on inter-individual variability. What does science actually tell us about the usefulness of eGFR in diagnosing CKD?

Early vs late initiation of sodium glycerophosphate: Impact on hypophosphatemia in preterm infants <32 weeks.

BACKGROUND & AIMS: Early electrolyte and mineral imbalances have emerged as a conspicuous problem in very preterm babies since the revision of nutrition guidelines and the eventual implementation of early aggressive parenteral nutrition (PN). We opted to carry out a study with the introduction of phosphorus as sodium glycerophosphate in PN from the first day onward to reveal the impact on serum phosphorus and calcium levels following the surge in the incidence of hypercalcemia and hypophosphatemia. METHODS: In this single-center, prospective, observational cohort study, inborn babies <32 gestational weeks and <1500 g between August 2017 and July 2018 were enrolled consecutively. Infants born in the first 6-month of this period were initiated PN (Early phosphorus group) containing phosphorus (1 mmol P as sodium glycerophosphate/100 ml PN) immediately after birth, and in the latter six-months, mineral-free standard PN (Control group) was commenced up until 48 h of life. Parenteral nutritional prescriptions of both groups were similar in terms of macro and micronutrient intakes except for early phosphorus, calcium, and sodium. Serum mineral and electrolyte levels were measured on Days 1-3-7 and compared between the groups. The primary outcome was the presence of hypophosphatemia in the first week of life. The secondary outcome was hypercalcemia, preterm morbidity, and mortality. RESULTS: A total of 261 infants were included in this study. There were 130 babies in Early phosphorus group and 131 in control group. Gestational ages (28.79 ± 2.1 vs 28.46 ± 2.2 weeks, respectively) and birth weights (1138 ± 273 vs 1090 ± 274 g, respectively) were similar in the groups. Mean serum phosphorus levels were higher on all days in Early phosphorus group (p < 0.001). Early phosphorus group had a lower incidence of hypophosphatemia on days 1-3 and 7 (p < 0.001). The percentage of hypercalcemic infants was significantly lower in Early phosphorus group on day 3 (p < 0.001). No difference was noted in terms of hypernatremia in the groups. CONCLUSIONS: Adding phosphorus to PN in the first hours of life reduced the frequency of hypophosphatemia and hypercalcemia without any surge in hypernatremia or morbidity. Nutrition guidelines need to be revised accordingly in terms of early mineral/electrolyte supplementation.

Serum calcium-phosphorus product for predicting the risk of osteoporotic vertebral compression fractures in elderly patients: a retrospective observational study.

BACKGROUND: This study retrospectively analyzed and evaluated the potential correlations of serum calcium, serum phosphorus, and calcium-phosphorus product (Ca-P product) with the incidence of osteoporotic vertebral compression fractures (OVCFs), with the aim of exploring whether the Ca-P product can be used as a serological indicator to predict the risk of OVCFs. METHODS: This study randomly enrolled 400 elderly patients in our hospital with OVCFs and 400 patients with hip and knee arthroplasty due to femoral head necrosis or osteoarthritis from August 2013 to April 2021. Age, sex, past medical history, and admission biochemical indicators, including albumin, blood urea nitrogen, serum creatinine, serum calcium and serum phosphorus, were collected for statistical analysis. RESULTS: Albumin, serum calcium, serum phosphorus, Ca-P product, corrected serum calcium and corrected Ca-P product were lower in the OVCF group than in the non-OVCF group (P < 0.05). Multivariate logistic regression analysis showed that low values of serum calcium, serum phosphorus, Ca-P product, corrected blood calcium, and corrected Ca-P product can all be risk factors for OVCF. The ROC curve showed that the Ca-P product and corrected Ca-P product were effective in predicting the risk of OVCFs. The predictive value of the Ca-P product was the best; the cutoff point was 29.88, the sensitivity was 0.72 and the specificity was 0.62. The cutoff point of the corrected Ca-P product was 30.50, the sensitivity was 0.74, and the specificity was 0.62. CONCLUSION: The Ca-P product and corrected Ca-P product can be used as serological indicators to predict the risk of OVCFs in elderly individuals. Early clinical interventions targeting this risk factor can further reduce the risk of OVCFs. Also, timely and regular testing of the serum calcium and phosphorus level is recommended and encouraged for this group of people.

Haplotypes in the GC, CYP2R1 and CYP24A1 Genes and Biomarkers of Bone Mineral Metabolism in Older Adults.

Candidate gene studies have analyzed the effect of specific vitamin D pathway genes on vitamin D availability; however, it is not clear whether genetic variants also affect overall bone metabolism. This study evaluated the association between genetic polymorphisms in GC, CYP2R1 and CYP24A1 and serum levels of total 25(OH)D, iPTH and other mineral metabolism biomarkers (albumin, total calcium and phosphorus) in a sample of 273 older Spanish adults. We observed a significant difference between CYP2R1 rs10741657 codominant model and total 25(OH)D levels after adjusting them by gender (p = 0.024). In addition, the two SNPs in the GC gene (rs4588 and rs2282679) were identified significantly associated with iPTH and creatinine serum levels. In the case of phosphorus, we observed an association with GC SNPs in dominant model. We found a relationship between haplotype 2 and 25(OH)D levels, haplotype 4 and iPTH serum levels and haplotype 7 and phosphorus levels. In conclusion, genetic variants in CYP2R1 and GC could be predictive of 25(OH)D and iPTH serum levels, respectively, in older Caucasian adults. The current study confirmed the role of iPTH as one of the most sensitive biomarkers of vitamin D activity in vivo.

Application of bone metabolic parameters in the diagnosis of growing pains.

OBJECTIVE: The present study aimed to assess the diagnostic significance of serum bone metabolic parameters in children with growing pains (GPs). METHODS: All patients diagnosed with GP and healthy controls matched with age and gender were recruited at the outpatient clinic of Children's Hospital at Zhejiang University School of Medicine from August 2016 to August 2021. In all subjects, serum levels of calcium (Ca), phosphorus (P), procollagen type-I N-terminal (PINP), parathormone (PTH), 25-hydroxyvitamin D (25-(OH)D), osteocalcin (OC), N-terminal cross-linked telopeptides of type-I collagen (CTX), and tartrate-resistant acid phosphatase type 5b (TRACP5b) were investigated. The univariate analysis, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve were used to identify the bone metabolic parameters factors for diagnosing GP. RESULTS: We enrolled 386 children with GP and 399 healthy controls in present study. The mean age of GP group was 5.319 years, and, primarily, the subjects were preschool-age children. The gender ratio (male-to-female) was 1.27 in GP group. After adjusting for age and gender, we identified that the serum levels of Ca (p < 0.001, OR: 25.039), P (p = 0.018, OR: 2.681), PINP (p < 0.001, OR: 1.002), and PTH (p = 0.036, OR: 0.988) were independent diagnostic factors associated with GP. Area under curve (AUC) of the ROC curves was in the order: PINP (0.612) > Ca (0.599) > P (0.583) > PTH (0.541). A combination of independent diagnostic factors and multivariable logistic regression analysis provided a refined logistic regression model to improve the diagnostic potential, of which the AUC had reached 0.655. CONCLUSIONS: Serum levels of Ca, P, PINP, and PTH could be independent diagnostic factors associated with GP. The logistic model was significantly superior to bone metabolic parameters for diagnosing GP.

Activation of the Calcium Receptor by Calcimimetic Agents Is Preserved Despite Modest Attenuating Effects of Hyperphosphatemia.

BACKGROUND: Phosphorus levels in the range seen clinically among patients undergoing dialysis have been reported to attenuate calcium receptor activation and modify parathyroid hormone (PTH) release from isolated parathyroid glands in vitro. Some clinicians and providers of dialysis thus have suggested that calcimimetic agents are ineffective and should not be used to manage secondary hyperparathyroidism among those undergoing dialysis when serum phosphorus concentrations exceed certain threshold levels. METHODS: To determine whether hyperphosphatemia diminishes the therapeutic response to calcimimetic agents, we used data from large clinical trials to analyze the effects of etelcalcetide and cinacalcet to lower plasma PTH levels in individuals on hemodialysis who had secondary hyperparathyroidism and varying degrees of hyperphosphatemia. RESULTS: Plasma PTH levels declined progressively during 26 weeks of treatment with either etelcalcetide or cinacalcet without regard to the degree of hyperphosphatemia at baseline. However, with each calcimimetic agent, the decreases in PTH from baseline were less at each interval of follow-up during the trials among participants with serum phosphorus levels above one of three prespecified threshold values compared with those with serum phosphorus levels below these thresholds. CONCLUSIONS: These in vivo findings are the first in humans to support the idea that hyperphosphatemia attenuates calcium receptor activation by calcium ions and by calcimimetic agents. The effect of hyperphosphatemia on the responsiveness to calcimimetic agents appears relatively modest, however, and unlikely to be significant therapeutically. The efficacy of treatment with calcimimetic agents for lowering plasma PTH levels among those with secondary hyperparathyroidism remains robust despite substantial elevations in serum phosphorus.

Impact of Longer Hemodialysis Vintage with Higher Serum Phosphorus Level on Clinical Outcomes in Patients with Chronic Limb-Threatening Ischemia Presenting Tissue Loss after Endovascular Therapy.

AIMS: Hemodialysis vintage and serum phosphorus levels adversely affect outcomes in patients on hemodialysis. Whether these factors have a similar prognostic impact on patients who are on hemodialysis and have chronic limb-threatening ischemia (CLTI) has not been systematically studied. We aimed to explore the risk factors, including hemodialysis vintage and serum phosphorus levels, on clinical outcomes after endovascular therapy (EVT) in hemodialysis patients with CLTI. METHODS: The current study rerospectively analyzed 374 hemodialysis patients with CLTI presenting with ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 68.2%, Rutherford 5: 75.9%, 6: 24.1%, WIfI stage 4: 50.0%) primarily treated with EVT between April 2007 and December 2016. The primary outcome measure was 1-year amputation-free survival (AFS), while the secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model. RESULTS: Multivariate analysis significantly associated longer hemodialysis vintages with higher serum phosphorus levels (hazard ratio [HR], 0.599; 95% confidence interval [CI], 0.394-0.910; p=0.016) with 1-year AFS. Longer vintages for hemodialysis with higher serum phosphorus levels were marginally, but not significantly, associated with 1-year wound healing. (HR, 0.684; 95% CI, 0.467-1.000; p=0.050). CONCLUSION: Longer hemodialysis vintages with higher serum phosphorus levels adversely affect outcomes after EVT for hemodialysis patients with CLTI presenting with ischemic tissue loss.

Population Pharmacokinetics and Pharmacodynamics of Burosumab in Adult and Pediatric Patients With X-linked Hypophosphatemia.

Burosumab is a fully human monoclonal antibody against fibroblast growth factor 23, which has been approved to treat X-linked hypophosphatemia (XLH) in adult and pediatric patients. The present work describes the pharmacokinetics (PK) of burosumab and the pharmacokinetic-pharmacodynamic (PK-PD) relationship between burosumab and serum phosphorus in adult and pediatric patients with XLH. A total of 2844 measurable serum concentrations of burosumab and 6047 measurable serum concentrations of phosphorus in 277 subjects from 9 clinical studies were included in the population PK and PK-PD modeling. The serum concentration of burosumab following a subcutaneous administration was well described by a population PK model comprising a first-order absorption, 1-compartmental distribution, and a linear elimination. The relationship between serum burosumab and serum phosphorus was adequately described by a sigmoid maximal efficacy model. Body weight was the only covariate associated with PK and PK-PD parameters. No other intrinsic factors affected PK or PK-PD relationship in adult and pediatric patients with XLH. Further simulations helped to guide the dosing regimen of burosumab in adult and pediatric patients with XLH including age groups with no clinical data.

Circulating phosphorus concentration and risk of prostate cancer: a Mendelian randomization study.

BACKGROUND: Recent observational studies have suggested that circulating phosphorus concentrations are positively associated with the risk of prostate cancer. However, little is known about the causal direction of the association. OBJECTIVES: To explore the potential causal relation between circulating phosphorus and risk of prostate cancer, we conducted a Mendelian randomization (MR) study. METHODS: Summary statistics of prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWASs) consisting of 79,148 cases and 61,106 controls. Single-nucleotide polymorphisms (SNPs) associated with serum phosphorus concentration were selected from a GWAS of 291,408 individuals from the UK Biobank. MR analysis was performed using the inverse variance weighted (IVW) method, supplemented with simple median method, weighted median method, maximum likelihood-based method, MR-Egger regression, and the MR pleiotropy residual sum and outlier test. We also performed a meta-analysis of observational studies to assess the associations of dietary phosphorus intake and serum phosphorus concentration with risk of prostate cancer. RESULTS: In the MR analysis, a total of 125 independent SNPs associated with serum phosphorus concentrations were used as instrumental variables. Genetically predicted serum phosphorus concentrations were associated with a 19% increased risk of prostate cancer (95% CI: 9%, 31%) per 1-SD increment of serum phosphorus by IVW (P = 1.82 × 10-4). Sensitivity analyses using alternative MR methods produced similar positive associations, and no evidence of pleiotropy was detected by MR-Egger regression (P = 0.422). For meta-analysis, 8 studies for dietary phosphorus intake and 4 for serum phosphorus concentrations were included involving a total of 669,080 participants. Consistently, high dietary phosphorus intake and serum phosphorus concentrations were associated with an 8% (95% CI: 4%, 12%) and 7% (95% CI: 1%, 14%) increase in prostate cancer risk, respectively. CONCLUSIONS: Our study suggested a potential causal relation between circulating phosphorus and risk of prostate cancer. Further studies are warranted to elucidate the underlying mechanism of phosphorus in the development of prostate cancer.

Number of cells in parathyroid tissue in primary hyperparathyroidism cases and its relationship with serum calcium value.

BACKGROUND: The relationship between serum calcium (Ca) level to serum parathyroid hormone (PTH), phosphorus (P) levels and tissue properties of the parathyroid gland is unknown in primary hyperparathyroidism cases. Revealing this relationship may be useful for understanding the etiopathogenesis of primary hyperparathyroidism and determining the time of treatment. METHODS: Ninety patients (71 females, 19 males, age range; 27-73 years, average age; 46) who underwent single gland excision with the diagnosis of primary hyperparathyroidism were studied. The patients were divided into 2 groups as serum Ca level <12 and serum Ca level ≥12. Age and sex of the patients, mean cell number of the gland, mean volume of the gland, serum levels of PTH, P, and histopathologic type of hyperplasia were evaluated. RESULTS: The mean cell number per cubic centimeter is 22.9 (10-220 range) million in all glands. Serum Ca level was <12 in 82 (91.1%) of the patients, and ≥12 in 8 (8.9%) cases. Mean cell number of the gland, mean volume of the gland, existence of cystic hyperplasia of the gland, serum levels of PTH and P were statistically significant between the 2 groups (P < .001, P < .001, P < .05, P < .001, P < .05 respectively). CONCLUSION: In primary hyperparathyroidism cases serum Ca level is not related to age and sex but directly related to proportionals to the cell number and volume of the gland and serum levels of PTH, inversely related to cystic hyperplasia and serum levels of P. Early surgical intervention should be planned since the serum Ca level will be high in large adenomas with a noncystic radiological appearance.

Higher Serum Phosphorus Is Not an Independent Risk Factor of Mortality in Heart Failure with Reduced Ejection Fraction.

Higher serum phosphorus has detrimental health effects. Even high-normal rage sP is associated with worse outcomes. The relationship of serum phosphorus with prognostic markers in heart failure remains unclear. We investigated the association of serum phosphorus with heart failure prognostic factors and risk of mortality related to serum phosphorus. In 1029 stable heart failure patients, we investigated the distribution of markers of more advanced heart failure stage across quintiles of serum phosphorus and estimated the relative risk of mortality in comparison to reference. Higher serum phosphorus levels sP were associated with markers of a worse outcome. The best survival was observed in low-normal serum levels. The unadjusted hazard ratio for mortality increased toward higher phosphorus quintiles but not to lower levels of sP. The correction for age, sex, BMI, percent weight loss, inflammation, kidney function, and LVEF did not modify the risk profile substantially. The adjustment for NYHA, natriuretic peptides, serum sodium, and treatment characteristics broke down the risk relationship completely. A higher serum phosphorus is associated with markers of a more risky profile of heart failure. Elevated serum levels of phosphorus sP does not provide independent prognostic information beyond the strongest markers of the severity of the syndrome. The potential involvement of higher serum phosphorus as a mediator in the pathophysiology of heart failure warrants further study.

Factors affecting vitamin D status in outpatients with abdominal aortic aneurysm and peripheral artery disease- a single centre study.

BACKGROUND AND AIMS: Vitamin D (VD) deficiency is considered an important risk factor for the development of atherosclerosis and aortic aneurysms. The deficiency is claimed to enhance degeneration and remodeling of collagen and elastin fibers in the artery wall, leading to its weakening and progressive dilatation. This study aimed to assess vitamin D status, in outpatients with abdominal aneurysms (AAA) and peripheral artery disease (PAD) not treated with VD, and factors affecting serum 25-OH-D levels. METHODS AND RESULTS: This cross-sectional study involved 59 outpatients with AAA and 150 with PAD. AAA was defined as local dilation of the aorta diameter >30 mm in imaging. None of the patients was prescribed VD containing medicines. Serum 25-OH, iPTH, phosphorus and calcium levels were assessed in all study participants. VD status was categorized according to commonly used cut-offs for serum 25-OH-D (<20 ng/mL - deficiency, <30 ng/mL -insufficiency). Serum 25-OH-D levels were similar in patient with AAA and PAD [1-3Q: 26.2 (18.8-37.6) vs 21.8 (15.9-31.4) ng/mL; p = 0.30], with deficiency noted in 25.4% with AAA and 41.8% with PAD (p < 0.05). Multiple regression analysis revealed that VD deficiency was explained by past stroke episodes [OR = 2.80 (95%CI: 1.22-6.41)]. Secondary hyperparathyroidism was diagnosed in 1.7% of patients with AAA and 1.9% with PAD. CONCLUSIONS: The frequency of VD deficiency in outpatient with AAA is not greater than in those with PAD. Past stroke episode is associated with an increased occurrence of VD deficiency in both outpatients with AAA and PAD other than sun exposure and diet.

Implementation and effectiveness of an intensive education program on phosphate control among hemodialysis patients: a non-randomized, single-arm, single-center trial.

BACKGROUND: Hyperphosphatemia is a common complication in patients on maintenance hemodialysis. Patients' adherence to phosphorus control can be improved by consistent education. However, few studies have focused on the model construction and effects of health education on phosphate control for hemodialysis patients. OBJECTIVE: To develop an intensive education program focusing on phosphate control among hemodialysis patients and to analyze the effectiveness of this program. DESIGN: A non-randomized, single-arm, single-center trial lasting for 6 months. SETTING: This program was conducted in a hemodialysis center in a teaching hospital in Zhuhai, China. PARTICIPANTS: Patients on maintenance hemodialysis with hyperphosphatemia. METHODS: An intensive hyperphosphatemia control education program lasting for 6 months was conducted among 366 hemodialysis patients applying the First Principles of Instruction model, which focused on mastering four stages: (a) activation of prior experience, (b) demonstration of skills, (c) application of skills and (d) integration of these skills into real-world activities. The controlled percentage of serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders before and after the education program were assessed. RESULTS: The proportion of controlled serum phosphorus was significantly increased from 43.5 to 54.9% (P<0.001). The scores on the knowledge of phosphate control were improved significantly from 59.0 ± 18.9 to 80.6 ± 12.4 (P < 0.001). The proportion of high adherence to phosphate binders was increased dramatically from 21.9 to 44.5% (P < 0.001). CONCLUSION: The intensive education program can effectively improve serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders among hemodialysis patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100042017 . Retrospectively registered January 12th, 2021.

Evaluation of Vitamin D (25OHD), Bone Alkaline Phosphatase (BALP), Serum Calcium, Serum Phosphorus, Ionized Calcium in Patients with Mandibular Third Molar Impaction. An Observational Study.

The aim of this study was to evaluate the levels of vitamin D (25OHD) and other bone biomarkers in patients with third molar impaction (TMI). Thirty males and 30 females with unilateral or bilateral impacted mandibular third molar, and 15 males and 15 females as a control group (CG) were recruited. Rx-OPT was used to evaluate dental position and Pederson index to measure the difficulty of the intervention. Bone biomarkers were measured through blood venous sample in TMI group and CG. Mann-Whitney test, Pearson's correlation coefficient, linear regression model were used to compare the different parameters in the two groups. 25OHD showed lower values in TMI group than in CG (p < 0.05) with values significantly lower in bilateral impaction (p < 0.05). Pearson's coefficient for 25OHD presented a negative correlation with the Pederson index (ρ = -0.75). Bone alkaline phosphatase (BALP) showed significantly lower dosage in TMI group than CG (p = 0.02), Pearson's coefficient for BALP presented a negative correlation with the Pederson index. Serum calcium, serum phosphorus, ionized calcium levels in TMI and CG groups were similar and Mann-Whitney test did not significantly differ between TMI and CG. TMI could be a sign of vitamin D deficiency and of low BALP levels that should be investigated.

Dominant factors of the phosphorus regulatory network differ under various dietary phosphate loads in healthy individuals.

BACKGROUND: The purpose of this study was to explore the contribution of each factor of the phosphorus metabolism network following phosphorus diet intervention via Granger causality analysis. METHODS: In this study, a total of six healthy male volunteers were enrolled. All participants sequentially received regular, low-, and high-phosphorus diets. Consumption of each diet lasted for five days, with a 5-day washout period between different diets. Blood and urinary samples were collected on the fifth day of consumption of each diet at 9 time points (00:00, 04:00, 08:00, 10:00, 12:00, 14:00, 16:00, 20:00, 24:00) for measurements of serum levels of phosphate, calcium, PTH, FGF23, BALP, α-Klotho, and 1,25 D and urinary phosphorus excretion. Granger causality and the centrality of the above variables in the phosphorus network were analyzed by pairwise panel Granger causality analysis using the time-series data. RESULTS: The mean age of the participants was 28.5 ± 2.1 years. By using Granger causality analysis, we found that the α-Klotho level had the strongest connection with and played a key role in influencing the other variables. In addition, urinary phosphorus excretion was frequently regulated by other variables in the network of phosphorus metabolism following a regular phosphorus diet. After low-phosphorus diet intervention, serum phosphate affected the other factors the most, and the 1,25 D level was the main outcome factor, while urinary phosphorus excretion was the most strongly associated variable in the network of phosphorus metabolism. After high-phosphorus diet intervention, FGF23 and 1,25 D played a more critical role in active regulation and passive regulation in the Granger causality analysis. CONCLUSIONS: Variations in dietary phosphorus intake led to changes in the central factors involved in phosphorus metabolism.