Analytical performance specifications for 25-hydroxyvitamin d examinations

Currently the 25-hydroxy vitamin D (25(OH)D) concentration is thought to be the best estimate of the vitamin D status of an individual. Unfortunately, its measurement remains complex, despite recent technological advances. We evaluated the biological variation (BV) of 25(OH)D in order to set analytical performance specifications (APS) for measurement uncertainty (MU). Six European laboratories recruited 91 healthy participants. The 25(OH)D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate on a Lumipulse G1200 (Fujirebio, Tokyo, Japan). The linear regression of the mean 25(OH)D concentrations at each blood collection showed that participants were not in a steady state. The dissection of the 10-sample collection into two subsets, namely collections 1–5 and 6–10, did not allow for correction of the lack of homogene-ity: estimates of the within-subject BV ranged from 5.8% to 7.1% and the between-subject BV ranged from 25.0% to 39.2%. Methods that would differentiate a difference induced by 25(OH)D supple-mentation at p < 0.05 should have MU < 13.6%, while at p < 0.01, the MU should be <9.6%. The development of APS using BV assumes a steady state of patients. The findings in this study suggest that patients are not in steady state. Therefore, APS that are based on MU appear to be more appro-priate

Practical Considerations for the Clinical Application of Bone Turnover Markers in Osteoporosis.

peer reviewedBone 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

The path to the standardization of PTH: Is this a realistic possibility? a position paper of the IFCC C-BM

Parathyroid hormone (PTH) determination is of greatest importance for patients suffering from parathyroid gland disorders and for the follow-up of bone turnover in patients suffering from chronic kidney disease (CKD). Two generations of PTH assays are simultaneously present on the market for PTH quantification. As these assays are not yet standardized, this results in a significant level of confusion in the care of CKD patients. One key objective of the IFCC Committee for Bone Metabolism is to improve this situation. In this position paper, we will highlight the current state of PTH testing and propose a pathway to ultimately overcome issues resulting from PTH assay variability

Effects of targeted therapies on bone in rheumatic and musculoskeletal diseases

Generalized bone loss (osteoporosis) and fragility fractures can occur in rheumatic and musculoskeletal diseases including rheumatoid arthritis and spondyloarthritis (SpA; including ankylosing spondylitis and psoriatic arthritis). In addition, rheumatoid arthritis can involve localized, periarticular bone erosion and, in SpA, local (pathological) bone formation can occur. The RANK–RANKL–osteoprotegerin axis and the Wnt–β-catenin signalling pathway (along with its inhibitors sclerostin and Dickkopf 1) have been implicated in inflammatory bone loss and formation, respectively. Targeted therapies including biologic DMARDs and Janus kinase (JAK) inhibitors can stabilize bone turnover and inhibit radiographic joint damage, and potentially also prevent generalized bone loss. Targeted therapies interfere at various points in the mechanisms of local and generalized bone changes in systemic rheumatic diseases, and they effect biomarkers of bone resorption and formation, bone mass and risk of fragility fractures. Studies on the effects of targeted therapies on rates of fragility fracture are scarce. The efficacy of biologic DMARDs for arresting bone formation in axial SpA is debated. Improved understanding of the most relevant therapeutic targets and identification of important targeted therapies could lead to the preservation of bone in inflammatory rheumatic and musculoskeletal diseases

Variations in 25-hydroxyvitamin d in countries from the middle east and europe: The roles of uvb exposure and diet

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Serum 25-hydroxyvitamin D (25(OH)D) has been largely associated with latitude and sunshine exposure across several regions. According to previous results, 25(OH)D concentrations are, on average, relatively low in countries with abundant sunshine, including those of the Middle East and North Africa region, as well as lower-latitude Europe. The standard explanation for this phenomenon is that people wear concealing clothing because of cultural and religious practices and that high temperatures in summer limit direct sun exposure. However, the role of diet in the development of profound hypovitaminosis D has not been adequately explored in those countries. To examine how diet affects vitamin D status in the Middle Eastern and European countries, a search was conducted for papers from that region reporting 25(OH)D concentrations. Papers were sought that reported summertime and wintertime 25(OH)D concentrations for healthy nonpregnant adults representative of the entire population. Data from 15 Middle Eastern and European countries were found through this search. Data for postmenopausal women from 19 European countries were also obtained. Dietary supply data for animal products containing vitamin D (animal fat, eggs, ocean fish, animal meat, and milk) were obtained from the Food and Agriculture Organization of the United Nations. Latitude and a solar UVB dose index also were obtained for each country. For the 15-country study, energy from dietary factors was highly correlated with latitude, making it difficult to separate the effects of UVB exposure and dietary factors. However, for the 19-country study, dietary factors were only weakly correlated with latitude. In that study, ocean fish was the most important single dietary factor affecting serum 25(OH)D concentration for postmenopausal women in various European countries, but animal fat and meat also contributed. Because this is an ecological study, further research is encouraged to evaluate and extend the findings

Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations

Recommendations on the measurement and the clinical use of vitamin D metabolites and vitamin D binding protein – A position paper from the IFCC Committee on bone metabolism

Vitamin D, an important hormone with a central role in calcium and phosphate homeostasis, is required for bone and muscle development as well as preservation of musculoskeletal function. The most abundant vitamin D metabolite is 25-hydroxyvitamin D [25(OH)D], which is currently considered the best marker to evaluate overall vitamin D status. 25(OH)D is therefore the most commonly measured metabolite in clinical practice. However, several other metabolites, although not broadly measured, are useful in certain clinical situations. Vitamin D and all its metabolites are circulating in blood bound to vitamin D binding protein, (VDBP). This highly polymorphic protein is not only the major transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites, but also participates in the transport of the 25(OH)D into the cell via a megalin/cubilin complex. The accurate measurement of 25(OH)D has proved a difficult task. Although a reference method and standardization program are available for 25(OH)D, the other vitamin D metabolites still lack this. Interpretation of results, creation of clinical supplementation, and generation of therapeutic guidelines require not only accurate measurements of vitamin D metabolites, but also the accurate measurements of several other “molecules” related with bone metabolism. IFCC understood this priority and a committee has been established with the task to support and continue the standardization processes of vitamin D metabolites along with other bone-related biomarkers. In this review, we present the position of this IFCC Committee on Bone Metabolism on the latest developments concerning the measurement and standardization of vitamin D metabolites and its binding protein, as well as clinical indications for their measurement and interpretation of the results

Harmonization of commercial assays for PINP; the way forward

peer reviewedSummary: International Federation of Clinical Chemistry and Laboratory Medicine and The International Osteoporosis Foundation Joint Committee on Bone Metabolism believes that the harmonization of PINP assays is an achievable and practical goal. Introduction: In order to examine the agreement between current commercial assays, a multi-center study was performed for PINP in serum and plasma. Methods: The automated methods for PINP (Roche Cobas and IDS iSYS) gave similar results. A significant proportional bias was observed between the two automated assays and the Orion radioimmunoassay (RIA) for PINP. Results: Results from other published studies comparing PINP values among these three assays broadly support our findings. Taken together, these results confirm that harmonized PINP measurements exist between the two automated assays (Roche Cobas and IDS iSYS) when the eGFR is > 30 mL/min/1.73m2, but a significant bias exists between the Orion RIA and the two automated assays. Conclusion: Therefore, in subjects with normal renal function, PINP results reported by the Roche Cobas and IDS iSYS assays are similar and may be used interchangeably, and similar reference intervals and treatment targets could be applied for the two automated assays. Harmonization between the automated assays and the RIA is potentially possible with the use of common calibrators and the development of a reference method for PINP. This should also help ensure that any new commercial assay developed in the future will attain similar results. IOF and IFCC are committed to working together towards this goal with the cooperation of the reagent manufacturing industry. © 2020, International Osteoporosis Foundation and National Osteoporosis Foundation