Role of Vitamin K in CKD: Is Its Supplementation Advisable in CKD Patients?

BACKGROUND: Patients with CKD are at an increased risk of developing vascular calcification (VC) and bone complications which translate into a higher morbidity and mortality. The dephosphorylated and uncarboxylated matrix Gla protein (dp-ucMGP) is considered to be an indicator of vitamin K2 status and correlates with markers of VC. It is activated by γ-glutamyl carboxylase that converts inactive MGP into an active form, and vitamin K2 is a cofactor of this reaction. The active form of MGP is a known inhibitor of arterial wall calcification and plays an important role in bone turnover. Recent studies show poor vitamin K2 status in CKD patients. We aimed to review the literature for the association between vitamin K2 status and calcification and bone disease risk and the efficacy of vitamin K2 supplementation in CKD population. SUMMARY: Most CKD patients, including those on renal replacement therapy, have vitamin K2 deficiency. The dp-ucMGP level, a marker of vitamin K2 status, is decreased by vitamin K2 supplementation in CKD patients, but there is no unequivocal proof that it influences arterial calcification progression and bone complications. Key Messages: CKD population are at risk of vitamin K deficiency. Supplementation of vitamin K2 is safe and improves the serum markers of its deficiency. There is lack of strong evidence that vitamin K2 supplementation slows progression of calcification or reduces the frequency of bone complications. More prospective studies are needed.

Osteoprotegerin in diabetic osteopathy.

AIM: The aim of this study is to evaluate the relationship between OPG and the degree of glycaemic control in a population of elderly subjects. METHODS AND RESULTS: Data presented included 172 elderly subjects, of whom 107 were hospitalized for a hip fracture and 65 were non fractured outpatients. All participants received a multidimensional geriatric evaluation and underwent blood sampling. HbA1c, OPG, CTX and OC were measured and DXA scans were performed. Carotid intima-media thickness (IMT) was measured in all outpatients. Diabetic patients had more comorbidities, higher mean values of lumbar spine and femoral neck BMD and T-score, lower circulating levels of OC and CTX, and higher circulating levels of OPG compared to non-diabetic subjects. OPG was directly correlated with HbA1c. This association was most evident in non-fractured elderly subjects. Moreover, diabetic patients with IMT>1.5 mm had greater mean values of OPG than non-diabetic subjects with high IMT and than elderly subjects with IMT < 1.5 mm, with and without T2DM. CONCLUSIONS: Diabetic patients have reduced circulating levels of OC and CTX, and elevated serum levels of OPG, suggesting a state of low bone turnover. Reduced bone turnover causes an increase of BMD and could lead to a poor bone quality. OPG and HbA1c were directly correlated and OPG mean values were higher in diabetic patients with poor glucose control. Diabetic osteopathy could be considered a late complication of T2DM, directly related with the degree of glucose control and the duration of the disease.

The Association Between Osteocalcin and C-Reactive Protein; A Relation of Bone with Inflammation: A Systematic Review and Meta-Analysis.

A meta-analysis was performed to summarize the evidence from observational studies regarding the association between serum osteocalcin (OC) and C-reactive protein (CRP). A systemic research of the literature databases including PubMed, SCOPUS, and Google Scholar was performed to identify the relevant studies up to March 2018. We used the random-effects model by the method of DerSimonian and Laird to calculate the overall effect size. Q-test and I 2-statistics were used to assess between-study heterogeneity. In addition, we did subgroup analysis to detect possible sources of heterogeneity based on BMI range, gender, type of study population and age. We identified 21studies of association between serum osteocalcin and CRP eligible for the meta-analysis. The overall effect size showed a significant inverse association between OC and CRP (Fisher's z=-0.127; 95% CI: -0.166, -0.088, p<0.0001). However, the significant chi-squared statistic result, indicates a heterogeneity of effect sizes (I 2=61.6, df=20, p<0.0001). The subgroup analysis found BMI range, type of study population, and age were the potential sources of heterogeneity. In addition, the strongest correlation was observed in the subgroup of obese subjects (Fisher's z=-0.264, p=0.002), less than 40 years old (Fisher's z=-0.115, p<0.0001) and healthy subjects (Fisher's z=-0.115, p<0.0001). These findings suggest that there is a significant inverse association between serum OC and CRP levels in the adult population.

Association between mineral and bone disorder in patients with acute kidney injury following cardiac surgery and adverse outcomes.

BACKGROUND: Numerous studies have evaluated the prevalence and importance of mineral and bone disorders among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, little is known about dysregulated mineral and bone metabolism in acute kidney injury (AKI). METHODS: We evaluated the association between mineral and bone metabolites and clinical outcomes in 158 patients who underwent cardiac surgery and developed AKI between June 2014 and January 2016. The baseline characteristics of the patients were recorded, and the levels of mineral and bone metabolites, including calcium, phosphate, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25D), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP-5b) and C-terminal fibroblast growth factor 23 (cFGF23) were measured within 12 h after establishing the clinical diagnosis. RESULTS: The serum phosphate, iPTH and cFGF23 levels were significantly associated with the 28-day mortality (phosphate: Hazard Ratio [HR] =2.620, 95% CI: 1.083 to 6.338, p = 0.035; iPTH: HR = 1.044, 95% CI: 1.001 to 1.090, p = 0.046; cFGF23: HR = 1.367, 95% CI: 1.168 to 1.599, p < 0.001). Moreover, higher serum cFGF23 and BAP levels were independently associated with an increased risk of adverse outcomes. Additionally, we found that the serum cFGF23 levels rose most significantly and were associated with the severity of AKI (P < 0.001). CONCLUSIONS: Mineral and bone metabolites are dysregulated and are associated with adverse clinical outcomes among patients with AKI. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00953992. Registered 6 August 2009.

Aberrant methylation-induced dysfunction of p16 is associated with osteoblast activation caused by fluoride.

Chronic exposure to fluoride continues to be a public health problem worldwide, affecting thousands of people. Fluoride can cause abnormal proliferation and activation of osteoblast and osteoclast, leading to skeletal fluorosis that can cause pain and harm to joints and bones and even lead to permanent disability. Nevertheless, there is no recognized mechanism to explain the bone lesions of fluorosis. In this work, we performed a population study and in vitro experiments to investigate the pathogenic mechanism of skeletal fluorosis in relation to methylation of the promoter of p16. The protein coded by the p16 gene inhibits cdk (cyclin-dependent kinase) 4/cdk6-mediated phosphorylation4 of retinoblastoma gene product and induces cell cycle arrest. The results showed that hypermethylation of p16 and reduced gene expression was evident in peripheral blood mononuclear cells of patients with fluorosis and correlated with the level of fluoride exposure. Studies with cell cultures of osteoblasts revealed in response to sodium fluoride (NaF) treatment, there was an induction of p16 hypermethylation and decreased expression, leading to increased cell proliferation, a longer S-phase of the cell cycle, and development of skeletal fluorosis. Further, the methylation inhibitor, 5-aza-2-deoxycytidine, reversed the p16 hypermethylation and expression in response to NaF. These results reveal a regulatory role of p16 gene methylation on osteoblasts activation during the development of skeletal fluorosis.

Anti-citrullinated alpha enolase antibodies, interstitial lung disease and bone erosion in rheumatoid arthritis.

Objectives: RA is an articular chronic inflammatory disease that in a subgroup of patients can also present with extra-articular manifestations (EAMs). Despite intense investigation on this topic, reliable biomarkers for EAMs are lacking. In recent years several ACPAs, including those targeting anti-citrullinated alpha enolase peptide-1 (anti-CEP-1), have been identified in patients with RA. Data about the ability of anti-CEP-1 to predict the development of erosive disease are confliciting and no evidence concerning their possible association with EAMs in RA is currently available. The aim of this study was to investigate the prevalence and significance of anti-CEP-1 with regard to the association with erosive disease and EAMs in a large cohort of patients with RA. Methods: Anti-CCP and anti-CEP-1 antibodies have been assessed on serum samples of RA patients, healthy donors and patients with SpA using commercially available ELISA kits. Results: Anti-CEP-1 antibodies are detectable in over 40% of RA patients and are associated with erosive RA and with RA-associated interstitial lung disease (ILD). Conclusion: Anti-CEP-1 antibodies may represent a useful biomarker for RA-associated ILD and erosive disease to be employed in clinical practice.

Using Mendelian Randomization to Decipher Mechanisms of Bone Disease.

PURPOSE OF REVIEW: This review summarizes the basic principles of Mendelian randomization (MR) and provides evidence for the causal effect of multiple modifiable factors on bone outcomes. RECENT FINDINGS: Several studies using MR approach have provided support for the causal effect of obesity on bone mineral density (BMD). Strikingly, studies have failed to prove a causal association between elevated 25(OH) D concentrations and higher BMD in community-dwelling individuals. The MR approach has been successfully used to evaluate multiple factors related to bone mineral density variation and/or fracture risk. The MR approach avoids some of the classical observational study limitations and provides more robust causal evidence, ensuring bigger success of the clinical trials. The selection of interventions based on genetic evidence could have a substantial impact on clinical practice.

Characteristics of bone turnover markers in rapidly destructive coxopathy.

The purpose of this study was to clarify bone turnover marker levels in rapidly destructive coxopathy (RDC). Twenty patients with RDC (mean age, 72 ± 11 years; 3 men, 17 postmenopausal women), 111 with osteoarthritis (OA) (age, 60 ± 10 years; 15 men, 13 premenopausal women, 83 postmenopausal women), and 18 with osteonecrosis of femoral head (ON) (55 ± 14 years; 11 men, 3 premenopausal women, 4 postmenopausal women), and 100 patients with femoral neck fracture (FNF) (81 ± 10 years; 27 men, 73 postmenopausal women) were included. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase (BAP), matrix metalloproteinase-3 (MMP-3) levels, and bone mineral density (BMD) of proximal femur and lumbar spine were investigated. TRACP-5b levels were significantly higher in RDC than in OA and ON, whereas BAP levels were higher in RDC than in OA (P < 0.05). MMP-3 levels were higher in RDC and ON than in OA (P < 0.05). TRACP-5b were higher in RDC than OA (P < 0.05) and FNF (P < 0.05) in performing propensity score matching; there were no differences in BMD between RDC and OA. TRACP-5b showed the largest area under the curve (AUC, 0.82) according to receiver operating characteristic (ROC) curve analysis for diagnosing RDC against OA and ON. AUCs of BAP and MMP-3 were 0.78 and 0.74. The respective sensitivities and specificities were 70.0 % and 85.3 % for TRACP-5b (cutoff, 623 mU/dl), 95.0 % and 57.1 % for BAP (13.8 U/l), and 70.0 % and 76.4 % for MMP-3 (52.7 ng/ml). The lack of differences in BMD suggested that high bone turnover marker levels may reflect osteoclast cell activation in RDC hips. Serum TRACP-5b and BAP could be RDC markers.

Clinical utility of C-terminal telopeptide of type 1 collagen in multiple myeloma.

Myeloma bone disease (MBD) is a major cause of morbidity in multiple myeloma (MM). We investigated bone turnover markers (BTM) as relapse predictors and biomarkers for monitoring MBD. We measured C-terminal telopeptide of type I collagen (CTX-1), and Procollagen type 1 N Propeptide (P1NP) in 86 MM patients and 26 controls. CTX-1 was higher in newly diagnosed patients compared to control, remission and relapse (P < 0·05), and decreased following treatment. In the setting of relapse, a CTX-1 rise greater than the calculated least significant change (LSC) was observed in 26% of patients 3-6 months prior to relapse (P = 0·007), and in 60·8% up to 3 months before relapse (P = 0·015). Statistically significant changes in CTX-1 levels were also observed in patients who were with and without bisphosphonate therapy at the time of relapse. In patients with normal renal function, mean CTX-1 level was highest in the newly diagnosed group (0·771 ± 0·400 µg/l), and lowest in the remission group (0·099 ± 0·070 µg/l) (P < 0·0001). P1NP levels were not statistically different across the patient groups. We conclude that CTX-1, measured on an automated hospital laboratory platform, has a role in routine treatment monitoring and predicting relapse of MBD, even in patients on bisphosphonates.

Sclerostin and DKK1: new players in renal bone and vascular disease.

For more than a decade, the Wnt-ß-catenin pathway has been the focus of intense basic and clinical research in the bone field because of its importance in skeletal development and maintenance of bone mass. Wnt activation increases bone formation and decreases bone resorption. The Wnt-ß-catenin signaling pathway is tightly regulated by several inhibitors, among which Dickkopf-related protein 1 (DKK1) and sclerostin have been most comprehensively studied. Mounting evidence indicates that a disturbed Wnt-ß-catenin signaling is also implicated in the pathogenesis of the chronic kidney disease-associated bone and mineral disorder (CKD-MBD) and affects its various components. DKK1 and sclerostin, more specifically, may be involved in the intense cross-talk between the kidneys, vasculature, and bone. Studies exploring clinical correlates of circulating sclerostin and DKK1 levels so far yielded conflicting results. Biological variability and analytical issues account at least partly for this inconsistency. Antibodies neutralizing Wnt inhibitors may be an appealing strategy to prevent or treat CKD-MBD. Caution is however warranted as sclerostin not only opposes mineralization in the bone but possibly also in the vasculature. Additional studies are required to define determinants of Wnt inhibitors in CKD and to evaluate the efficacy and safety of recently introduced pharmaceuticals targeting these inhibitors.

Circulating monocytes: an appropriate model for bone-related study.

Peripheral blood monocytes (PBMs) are an important source of precursors of osteoclasts, the bone-resorbing cells and the cytokines produced by PBMs that have profound effects on osteoclast differentiation, activation, and apoptosis. So PBMs represent a highly valuable and unique working cell model for bone-related study. Finding an appropriate working cell model for clinical and (epi-)genomic studies of human skeletal disorders is a challenge. Peripheral blood monocytes (PBMs) can give rise to osteoclasts, the bone-resorbing cells. Particularly, PBMs provide the sole source of osteoclast precursors for adult peripheral skeleton where the bone marrow is normally hematopoietically inactive. PBMs can secrete potent pro- and anti-inflammatory cytokines, which are important for osteoclast differentiation, activation, and apoptosis. Reduced production of PBM cytokines represents a major mechanism for the inhibitory effects of sex hormones on osteoclastogenesis and bone resorption. Abnormalities in PBMs have been linked to various skeletal disorders/traits, strongly supporting for the biological relevance of PBMs with bone metabolism and disorders. Here, we briefly review the origin and further differentiation of PBMs. In particular, we discuss the close relationship between PBMs and osteoclasts, and highlight the utility of PBMs in study the pathophysiological mechanisms underlying various skeletal disorders.

Elevated fluoride levels and periostitis in pediatric hematopoietic stem cell transplant recipients receiving long-term voriconazole.

Azole therapy is widely utilized in hematopoietic stem cell transplant (HCT) recipients for the treatment of aspergillus. Complications of voriconazole treatment related to its elevated fluoride content have been described in adults, including reports of symptomatic skeletal fluorosis. We review fluoride levels, clinical, and laboratory data in five pediatric HCT recipients on long-term voriconazole therapy, all found to have elevated serum fluoride levels. Two patients had toxic fluoride levels, one infant had symptoms of significant pain with movement and radiographs confirmed skeletal fluorosis. Monitoring fluoride levels in children, especially with skeletal symptoms, should be considered in patients on long-term voriconazole.

May osteoarticular infections be influenced by vitamin D status? An observational study on selected patients.

BACKGROUND: Vitamin D deficiency has been associated with a high number of health outcomes, and its role on the immune system has been deeply investigated in recent years, although poor data are still available on vitamin D status in orthopedic infections including those of prosthetic implants. METHODS: We focused on preoperative values of 25(OH)D in selected groups of patients with septic (Group A) or aseptic (Group B) prosthetic loosening, infective bone disease such as septic arthritis and osteomyelitis (Group C) and other orthopedic pathologies (Group D) to evaluate differences in the vitamin D status. RESULTS: A high prevalence of vitamin D deficiency was recorded among the study population (16.5 ± 5.4 ng/mL, mean ± SD). Interestingly, all patients with an infection presented a higher 25(OH)D concentration (17.7 ± 5.3 ng/mL) in respect to uninfected ones (15.1 ± 5.6 ng/mL). Significantly higher levels of 25(OH)D were observed in patients with prosthetic joint infection (18.5 ± 6.5 ng/mL), when compared with those presenting an aseptic loosening (13.6 ± 9.4 ng/mL). CONCLUSIONS: Deficiency in vitamin D levels have been found in orthopaedic patients. Prosthetic joint infections seems to be associated to higher values of vitamin D in respect to other bone infections or to other orthopaedic conditions requiring surgery. More studies are needed to improve the knowledge on vitamin D status in these patients and to better clarify the role of vitamin D in relation to osteoarticular infections.

[THE CHOLINESTERASE OF BLOOD SERUM IN WORKERS OF INDUSTRIAL ENTERPRISE].

The biochemical study of activity of serum cholinesterase in workers of industrial enterprise was carried out on the example of petrochemical industry. The indicators of average activity of enzyme and prevalence of indicators going beyond limits of reference values were analyzed depending on manufacturing-labor experience, profession and diseases established in workers. The main diseases, professional and labor experience groups were identified where activity of cholinesterase significantly changes. The impact of labor experience and profession on level of activity ofenzyme in blood serum is demonstrated.

Association of serum bicarbonate with bone fractures in hemodialysis patients: the mineral and bone disorder outcomes study for Japanese CKD stage 5D patients (MBD-5D).

BACKGROUND/AIMS: Bone fracture is often complicated in hemodialysis (HD) patients. Metabolic acidosis is related to bone disease and muscle wasting, but it is not known whether acid-base disturbance is associated with the risk of bone fractures. The aim of this study was to clarify the association of serum bicarbonate level with bone fracture in HD patients. METHODS: Using a subcohort of the Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D), 890 prevalent HD patients (age: 62 years old, male: 62.8%, duration of dialysis: 8.3 years) with secondary hyperparathyroidism were studied. After measuring predialysis serum bicarbonate at a 2-day interdialytic interval, we prospectively followed them every 3 months, and examined the occurrence of any type of bone fracture or hospitalization due to fracture over a 3-year observation period. RESULTS: Seventy-four bone fractures and 47 hospitalizations due to fracture were observed during the follow-up period. HD patients with serum bicarbonate <20 mmol/l had a 1.93 (95% CI 1.01-3.71)-fold higher risk for all-cause fractures than those with serum bicarbonate of 20.0-21.9 mmol/l. A higher bicarbonate level (≥22 mmol/l) was also related to an increased risk of bone fracture. A restricted cubic regression spline disclosed that the higher or the lower than 21.0 mmol/l of serum bicarbonate, the greater the risk for bone fracture. CONCLUSION: Both a lower level and a higher level of predialysis bicarbonate concentration were associated with risk of bone fracture in HD patients with secondary hyperparathyroidism.

Serum magnesium concentration is inversely associated with fibroblast growth factor 23 in haemodialysis patients.

AIM: Fibroblast growth factor 23 is reported to be a pivotal regulator for the chronic kidney disease-mineral bone disorders, working in coordinated ways with phosphate, calcium, and parathyroid hormone. However, whether there is a relationship between fibroblast growth factor 23 and magnesium is currently unclear. To address this, we performed a cross-sectional observational study in haemodialysis patients. METHODS: We measured the serum levels of fibroblast growth factor 23, magnesium and other factors that are implicated in chronic kidney disease-mineral bone disorders in 225 haemodialysis patients. RESULTS: Simple correlation analysis showed that fibroblast growth factor 23 was not correlated with magnesium. However, upon multiple regression analysis, a significant negative correlation was found between fibroblast growth factor 23 and magunesium (b = -0.164, P = 0.0020). Moreover, the levels of fibroblast growth factor 23 in patients treated with magnesium oxide had significantly lower levels than those without magnesium oxide. CONCLUSION: We speculate that the magnesium is a potential regulator of fibroblast growth factor 23 levels in haemodialysis patients. Our data suggest that follow-up studies to elucidate the molecular mechanisms that underlie this relationship are warranted.

Evaluation of bone mineral loss in patients with chronic traumatic spinal cord injury in Iran.

OBJECTIVES: We described the associations between demographic and injury-related factors on bone mineral density (BMD) of the spine and the hip among adult patients with chronic spinal cord injury (SCI). DESIGN: BMD in spinal and femoral bone sites were assessed. Multivariate analysis was performed to evaluate the relationship between anthropometric and injury-related factors with BMD. Serum level and amount of dietary intake of calcium, phosphor, and 25-hydroxy vitamin D were measured. SETTING: A referral tertiary rehabilitation center in Iran. PARTICIPANTS: Patients with SCI who had no previous history of endocrine disorders and were not on specific medications entered the investigation. Those with non-traumatic SCI, pregnant, or with substance dependency were excluded as well. INTERVENTIONS: No interventions were applied. MAIN STUDY OUTCOME MEASURES: Dual X-ray absorptiometry was performed to estimate BMD. Body mass index was positively associated with higher femoral (P < 0.01, r = 0.56) and hip (P < 0.0001, r = 0.82) BMD only in female participants. The high prevalence of vitamin D deficiency (60%) was noticeable. RESULTS: Older male patients revealed lower BMD only in spinal vertebrae (P < 0.02, r = -0.21). A significant higher BMD loss in lumbar vertebras in male patients with complete spinal cord lesion (P < 0.009) was detected. Spinal reduction of BMD was more severe when the level of injury was above T6 (P < 0.02). CONCLUSION: Along with the clarification of age, gender, post injury duration, and the other factors' effect on the BMD in the SCI patients, here we have also shown the noticeable prevalence of the 25-hydoxy vitamin D deficiency in these patients which needs attention.

The correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients.

Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. METHODS: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), ß-C-terminal telopeptide of type I collagen (ß-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. RESULTS: The area under the curve (AUC) predicted by ß-C-terminal telopeptide of type I collagen (ß-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p < .001, p = .004, p = .027, respectively). Cox multivariate analysis indicated that serum ß- CTX、lactic dehydrogenase、hemoglobin and the degree of bone injury were independent prognostic factors. A COX regression model was established with a C-index of 0.782 and validated with a C-index of 0.711. CONCLUSION: The serum BMIs are correlated with the patients' OS, and ß- CTX can be an independent prognostic factor.

Association between serum iron status and the risk of five bone and joint-related diseases: a Mendelian randomization analysis.

Background: According to reports, iron status has been associated with the risk of bone and joint-related diseases. However, the exact role of iron status in the development of these conditions remains uncertain. Method: We obtained genetic data on iron status, specifically serum iron, ferritin, transferrin saturation (TSAT), and transferrin, as well as data on five common bone and joint-related diseases (osteoarthritis, osteoporosis, rheumatoid arthritis [RA], ankylosing spondylitis [AS], and gout) from independent genome-wide association studies involving individuals of European ancestry. Our primary approach for causal estimation utilized the inverse variance weighted (IVW) method. To ensure the reliability of our findings, we applied complementary sensitivity analysis and conducted reverse causal analysis. Result: Using the IVW method, we revealed a positive causal relationship between ferritin levels and the risk of osteoarthritis (OR [95% CI], 1.0114 [1.0021-1.0207]). Besides, we identified a protective causal relationship between serum iron levels and TSAT levels in the risk of RA (OR [95% CI] values of serum iron and TSAT were 0.9987 [0.9973-0.9999] and 0.9977 [0.9966-0.9987], respectively). Furthermore, we found a positive causal relationship between serum iron levels and the risk of AS (OR [95% CI], 1.0015 [1.0005-1.0026]). Regarding gout, both serum iron and TSAT showed a positive causal relationship (OR [95% CI] values of 1.3357 [1.0915-1.6345] and 1.2316 [1.0666-1.4221] for serum iron and TSAT, respectively), while transferrin exhibited a protective causal relationship (OR [95% CI], 0.8563 [0.7802-0.9399]). Additionally, our reverse causal analysis revealed a negative correlation between RA and ferritin and TSAT levels (OR [95% CI] values of serum iron and TSAT were 0.0407 [0.0034-0.4814] and 0.0049 [0.0002-0.1454], respectively), along with a positive correlation with transferrin (OR [95% CI], 853.7592 [20.7108-35194.4325]). To ensure the validity of our findings, we replicated the results through sensitivity analysis during the validation process. Conclusion: Our study demonstrated a significant correlation between iron status and bone and joint-related diseases.

Control of mineral metabolism and bone disease in haemodialysis patients: which optimal targets?

BACKGROUND: There is a high drug treatment burden on patients receiving long-term dialysis therapy. Abnormalities of calcium and phosphate metabolism are associated with increased mortality, and attempts to correct these disturbances may improve survival. METHODS: We prospectively evaluated the targets of the currently used Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in 8377 prevalent patients receiving intermittent haemodialysis therapy in France from July 2007 to December 2009. RESULTS: Adjusted Cox analyses showed that only one among six targets was predictive of mortality, i.e. a serum intact parathyroid hormone (iPTH) <130 pg/mL. A continuous risk analysis using fractional polynomials showed a 10% increase in hazard ratio (HR) for mortality for a serum phosphate <0.71 (2.2) and >1.98 (6.14) mmol/L (mg/dL), a non-corrected serum calcium <1.59 (6.37) and >2.41 (9.66) mmol/L (mg/dL) and a serum iPTH <100 and >1090 pg/mL. CONCLUSION: The findings of our observational study confirm the existence of a grey zone, in which precise biochemical targets are difficult to define, with the exception of avoiding extreme values. Given the absence of intervention trials proving the clinical usefulness of phosphorus control, and pending the results of large clinical trials on the effect of optimal PTH and calcium control on hard outcomes, the present findings may help to refine future recommendations for the treatment of chronic haemodialysis patients.