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Two decades after the discovery of the hormone FGF23, we know more about phosphate homeostasis as it turned out that FGF23 is the central hormone that regulates this. Hereditary hypophosphatemic rickets and tumor-induced osteomalacia could by then be explained, by autonomous FGF23 production, and the nephrology field was excited by this new marker as it turned out to be independently associated with mortality in people treated by hemodialysis. This led to the development of several immunoassays to be able to measure FGF23 in blood. In the past years we learned that FGF23 is a rather stable peptide, the precision of the assays is acceptable but assays are not standardized and therefore not comparable. This means that reference values and cutoff values need to be assay specific. For several assays reference values have been established and gender and age did not seem of high importance. The phosphate content of the diet, which can be culturally dependent, however, should be taken into account when interpreting results, but to what extent is not totally clear. Currently, clinical application of the immunoassays is established in the diagnosis of hereditary hypophosphatemic rickets and diagnosis and follow-up of tumor-induced osteomalacia. Definite conclusions on the usefulness of the FGF23 measurement in people with CKD either as a marker for risk prediction or a as target for treatment remains to be determined. The latter applications would require dedicated prospective clinical trials, which may take years, before providing answers. To improve the standardization of the FGF23 assays and to shed light on the biological functions that fragments might have we might aim for an LC–MS/MS-based method to quantify both intact and fragmented FGF23. In this literature review we will summarize the current knowledge on the physiological role of FGF23, its quantification, and the clinical usefulness of its determination.

PurposeMany patients with coronavirus disease 2019 (COVID-19) required critical care. Mid-term outcomes of the survivors need to be assessed. The objective of this single-center cohort study was to describe their physical, cognitive, psychological, and biological outcomes at 3 months following intensive care unit (ICU)-discharge (M3).Patients and methodsAll COVID-19 adults who survived an ICU stay ≥ 7 days and attended the M3 consultation at our multidisciplinary follow-up clinic were involved. They benefited from a standardized assessment, addressing health-related quality of life (EQ-5D-3L), sleep disorders (PSQI), and the three principal components of post-intensive care syndrome (PICS): physical status (Barthel index, handgrip and quadriceps strength), mental health disorders (HADS and IES-R), and cognitive impairment (MoCA). Biological parameters referred to C-reactive protein and creatinine.ResultsAmong the 92 patients admitted to our ICU for COVID-19, 42 survived a prolonged ICU stay and 32 (80%) attended the M3 follow-up visit. Their median age was 62 [49–68] years, 72% were male, and nearly half received inpatient rehabilitation following ICU discharge. At M3, 87.5% (28/32) had not regained their baseline level of daily activities. Only 6.2% (2/32) fully recovered, and had normal scores for the three MoCA, IES-R and Barthel scores. The main observed disorders were PSQI > 5 (75%, 24/32), MoCA < 26 (44%, 14/32), Barthel < 100 (31%, 10/32) and IES-R ≥ 33 (28%, 9/32). Combined disorders were observed in 13/32 (40.6%) of the patients. The EQ-5D-3L visual scale was rated at 71 [61–80]. A quarter of patients (8/32) demonstrated a persistent inflammation based on CRP blood level (9.3 [6.8–17.7] mg/L).ConclusionThe burden of severe COVID-19 and prolonged ICU stay was considerable in the present cohort after 3 months, affecting both functional status and biological parameters. These data are an argument on the need for closed follow-up for critically ill COVID-19 survivors.

Bone turnover markers (BTMs) are released during the bone remodelling cycle and are measurable in blood or urine, reflecting bone remodelling rate. They have been useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medication in clinical trials and are increasingly used in routine clinical management of osteoporosis, especially for monitoring therapy, in addition to their use in other metabolic bone disease such as Paget’s disease of bone and osteomalacia. Serum β isomerised C-terminal telopeptide of type I collagen and pro-collagen I N-terminal propeptide have been designated as reference BTMs for use in osteoporosis. In addition, bone-specific isoenzyme of alkaline phosphatase (B-ALP) secreted by osteoblasts and tartrate-resistant acid phosphatase 5b (TRACP-5b) secreted by osteoclasts are also found to be specific markers of bone formation and resorption, respectively. The concentrations of the latter enzymes in blood measured by immunoassay provide reliable measures of bone turnover even in the presence of renal failure. B-ALP is recommended for use in the assessment of renal bone disease of chronic kidney disease, and TRACP-5b shows promise as a marker of bone resorption in that condition. BTMs in blood do not suffer from biological variation to the same extent as the older BTMs that were measured in urine. Appropriate patient preparation and sample handling are important in obtaining accurate measures of BTMs for clinical use. Reference change values and treatment targets have been determined for the reference BTMs for their use in monitoring osteoporosis treatment. Further ongoing studies will enhance their clinical applications.

Estimating equations for the glomerular filtration rate — EKFC eGFRcr (creatinine) and EKFC eGFRcys (cystatin C) — were tested. EKFC eGFRcys was unbiased and accurate, irrespective of the inclusion of race or sex.

Vitamin D deficiency and insufficiency has become a pandemic health problem with a consequent increase of requests for determining circulating levels of 25-hydroxyvitamin D [25(OH)D]. However, the analytical performance of these immunoassays, including radioimmunoassay and ELISA, is highly variable, and even mass spectrometric methods, which nowadays serves as the gold standard for the quantitatively determination of 25(OH)D, do not necessarily produce comparable results, creating limitations for the definition of normal vitamin D status ranges. To solve this problem, great efforts have been made to promote standardization of laboratory assays, which is important to achieve comparable results across different methods and manufacturers. In this review, we performed a systematic analysis evaluating critically the advantages and limits of the current assays available for the measure of vitamin D status, i.e., circulating 25(OH)D and its metabolites, making suggestions that could be used in the clinical practice. Moreover, we also suggest the use of alternatives to blood test, including standardized surveys that may be of value in alerting health-care professionals about the vitamin D status of their patients.

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients’ experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.This Consensus Statement provides robust clinical evidence on the multidisciplinary management of children and adults with X-linked hypophosphataemia, with an emphasis on patients’ experiences and needs. It is the outcome of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases.

BackgroundNeurofilament light chain (NF-L) concentration is recognized to be modified in neurological diseases and traumatic brain injuries, but studies in the normal aging population are lacking. It is, therefore, urgent to identify influencing factors of NF-L concentration in the aging population.MethodWe assessed NF-L concentration in sera of a large cohort of 409 community-dwelling adults aged over 65 years. We studied the association between NF-L and various physiological factors but also with self-reported comorbidities or life-style habits.ResultsWe showed that NF-L concentration in serum was tightly associated with cystatin C concentration (r = 0.501, p < 0.0001) and consequently, to the estimated glomerular filtration rate (eGFR) (r = − 0.492; p < 0.0001). Additionally, NF-L concentration was dependent on age and body mass index (BMI) but not sex. Among the self-reported comorbidities, subjects who reported neurological disorders, cardiovascular diseases or history of fracture had higher NF-L concentration in univariate analysis, whereas it was only the case for subjects who reported neurological disorders in the multivariate analysis. NF-L concentration was also increased when Mini-Mental State Examination (MMSE) was decreased (≤ 25 points) but not when geriatric depression score (GDS) was increased (> 5 points) in both univariate and multivariate analysis. Finally, we are providing reference ranges by age categories for subjects with or without altered renal function.ConclusionNF-L concentration in the aging population is not driven by the increasing number of comorbidities or depression. Yet, NF-L blood concentration is dependent on kidney function and NF-L interpretation in patients suffering from renal failure should be taken with caution.

Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an “anabolic first” approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon.

Background The Global Leadership Initiative on Malnutrition (GLIM) criteria have been recently launched by consensus of the major nutrition societies. GLIM criteria are partly constructed on the previous definition of malnutrition developed by the European Society of Clinical Nutrition and Metabolism (ESPEN). We aimed to assess malnutrition according to the ESPEN and GLIM criteria at baseline and to determine the corresponding risk of mortality during a 4‐year follow‐up in community‐dwelling older adults from the SarcoPhAge (Sarcopenia and Physical Impairment with advancing Age) study. The relationship between malnutrition and incidence of 4‐year adverse health consequences (institutionalization, hospitalization, falls, and fractures) was assessed. Methods This prospective population‐based cohort was part of SarcoPhAge, which included 534 older adults in Belgium, followed up from 2013 to 2019. Community‐dwelling healthy volunteers ≥65 years old were recruited. Mortality and adverse health consequences were collected annually by interview or phone call. Baseline malnutrition was defined according to the GLIM and ESPEN criteria. Agreement between the two definitions was reported by Cohen's kappa coefficient. Adjusted Cox regression and Kaplan–Meier survival curves were performed for malnutrition. Logistic regression was used for the other outcomes. Results From 534 subjects in SarcoPhAge, the records for 411 participants (73.2 ± 6.05 years old; 55.7% women) had all the variables needed to apply the GLIM criteria. Prevalence of baseline malnutrition was 23.4% for GLIM and 7% for ESPEN criteria (k = 0.30, low agreement). The adjusted Cox regression showed a significant increased mortality risk according to malnutrition status as defined by the GLIM [adjusted hazard ratio = 4.41 (95% confidence interval: 2.17–8.97)] and ESPEN [adjusted hazard ratio = 2.76 (95% confidence interval: 1.16–6.58)] criteria. Survival curves differed significantly between malnourished and non‐malnourished groups, regardless of the definition used (log rank P < 0.001 for both). No association was found between baseline malnutrition according to these two criteria and 4‐year risk of institutionalization, hospitalization, falls, or fractures (all P > 0.05). Conclusions Malnutrition according to the GLIM criteria was associated with a 4.4‐fold higher mortality risk, double that of the ESPEN criteria, during a 4‐year follow‐up. No association was found between malnutrition according to these two criteria and incidence of other health adverse consequences. GLIM criteria anticipate mortality and might guide interventions, with important implications for clinical practice and research.

The differential diagnosis of erosive osteoarthritis of the hand (EHOA) and psoriatic arthritis (PsA) is challenging, especially considering the absence of specific diagnostic biomarkers. The aim of the present study was to evaluate whether a pattern of microRNAs (miRNAs) (miR-21, miR-140, miR-146a, miR-155, miR-181a, miR-223), pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-17a, IL-23a, and tumor necrosis factor (TNF)-α], and adipokines (adiponectin, chemerin, leptin, resistin, and visfatin) could help to differentiate EHOA from PsA. Fifty patients with EHOA, fifty patients with PsA, and fifty healthy subjects (HS) were studied. The gene expression of miRNAs and cytokines were evaluated by real-time PCR from peripheral blood mononuclear cells and serum levels of cytokines and adipokines were quantified by ELISA in PsA and EHOA patients and HS. Gene expression showed the significant up-regulation of the analyzed miRNAs in EHOA and PsA patients as compared to HS and higher miR-155 in EHOA vs. PsA patients. The expression levels of IL-1β and IL-6 did not show any significant differences between EHOA and PsA, while IL-17a and IL-23a were significantly up-regulated in PsA compared to EHOA. Circulating TNF-α levels were higher in EHOA compared to PsA, while PsA patients exhibited significantly elevated levels of IL-23a. The combination of miR-155 with C-reactive protein enhanced the ability to differentiate EHOA from PsA, further supporting the potential of miR-155 as a diagnostic biomarker.