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Introduction\ud \ud Increased biochemical bone turnover markers (BTMs) measured in serum are associated with bone loss, increased fracture risk and poor treatment adherence, but their role in clinical practice is presently unclear. The aim of this consensus group report is to provide guidance to clinicians on how to use BTMs in patient evaluation in postmenopausal osteoporosis, in fracture risk prediction and in the monitoring of treatment efficacy and adherence to osteoporosis medication.\ud \ud \ud \ud Methods\ud \ud A working group with clinical scientists and osteoporosis specialists was invited by the Scientific Advisory Board of European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).\ud \ud \ud \ud Results\ud \ud Serum bone formation marker PINP and resorption marker βCTX-I are the preferred markers for evaluating bone turnover in the clinical setting due to their specificity to bone, performance in clinical studies, wide use and relatively low analytical variability. BTMs cannot be used to diagnose osteoporosis because of low sensitivity and specificity, but can be of value in patient evaluation where high values may indicate the need to investigate some causes of secondary osteoporosis. Assessing serum levels of βCTX-I and PINP can improve fracture prediction slightly, with a gradient of risk of about 1.2 per SD increase in the bone marker in addition to clinical risk factors and bone mineral density. For an individual patient, BTMs are not useful in projecting bone loss or treatment efficacy, but it is recommended that serum PINP and βCTX-I be used to monitor adherence to oral bisphosphonate treatment. Suppression of the BTMs greater than the least significant change or to levels in the lower half of the reference interval in young and healthy premenopausal women is closely related to treatment adherence.\ud \ud \ud \ud Conclusion\ud \ud In conclusion, the currently available evidence indicates that the principal clinical utility of BTMs is for monitoring oral bisphosphonate therapy.

A stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of 24,25-dihydroxyvitamin D-3 (24,25(OH)(2)D-3) and 25-hydroxyvitamin D-3/D-2 (25(OH)D-3/D-2) in human aqueous humor samples from the Eye-D study. Optimum sample preparation is based on simple liquid-liquid extraction (LLE) followed by derivatization with an Amplifex reagent prior to LC-MS/MS in order to enhance analyte sensitivity. The average recoveries for 24,25(OH)(2)D-3 (0.02, 0.05, 0.4 mu g L-1), 25(OH)D-3 (0.2, 0.5,3.75 mu g L-1) and 25(OH)D-2 (0.15, 0.4, 3 mu g L-1) ranged from 92 to 112 with a coefficient of variance (CV) lower than 15%. The limits of quantitation (LOQs) were from 0.02 mu g L-1 (24,25(OH)(2)D-3) to 0.2 mu g L-1 (25(OH)D-3) using a sample volume of 50 mu L. We demonstrated that the present method provides adequate sensitivity, selectivity, accuracy, and robustness to screen for vitamin D metabolites in aqueous humor samples by analyzing five samples which were withdrawn during cataract operation.

Chronic kidney disease (CKD) is often associated with a mineral and bone disorder globally described as CKD-Mineral and Bone Disease (MBD), including renal osteodystrophy, the latter ranging from high bone turnover, as in case of secondary hyperparathyroidism (SHPT), to low bone turnover. The present article summarizes the important subjects that were covered during The Parathyroid Day in Chronic Kidney Disease' CME course organized in Paris in September 2017. It includes the latest insights on parathyroid gland growth, parathyroid hormone (PTH) synthesis, secretion and regulation by the calcium-sensing receptor, vitamin D receptor and fibroblast growth factor 23 (FGF23)-Klotho axis, as well as on parathyroid glands imaging. The skeletal action of PTH in early CKD stages to the steadily increasing activation of the often downregulated PTH receptor type 1 has been critically reviewed, emphasizing that therapeutic strategies to decrease PTH levels at these stages might not be recommended. The effects of PTH on the central nervous system, in particular cognitive functions, and on the cardiovascular system are revised, and the reliability and exchangeability of second- and third-generation PTH immunoassays discussed. The article also reviews the different circulating biomarkers used for the diagnosis and monitoring of CKD-MBD, including PTH and alkaline phosphatases isoforms. Moreover, it presents an update on the control of SHPT by vitamin D compounds, old and new calcimimetics, and parathyroidectomy. Finally, it covers the latest insights on the persistence and de novo occurrence of SHPT in renal transplant recipients.

Biochemical bone turnover markers (BTM) are useful tools to assess bone remodeling at the cellular level. N-terminal propeptide of type I procollagen (PINP) has been recommended as a reference marker for bone formation in research studies. We describe the results of a multicenter study for routine clinical laboratory assays for PINP in serum and plasma. Four centers (Athens, Greece [GR], Copenhagen, Denmark [DK], Liege, Belgium [BE] and Sheffield, United Kingdom [UK]) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers' instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method and the concordance correlation coefficient for PINP values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. We showed that both EDTA plasma and serum were suitable for PINP determination. We observed a significant proportional bias between Orion radioimmunoassay and the automated methods for PINP (Roche Cobas and IDS iSYS), which both gave very similar results. The multivariate model did not improve the excellent correlation that was observed between the methods. Harmonization of PINP assays is possible by applying a correction factor or correctly assigning the values of the calibrators. This work will benefit from further collaboration between assays manufacturers and clinical laboratory professionals. © 2019 Walter de Gruyter GmbH, Berlin/Boston.

A Liquid Chromatography coupled to tandem mass spectrometry (LC-MS/MS) based method have been developed for the determination of the main estrogen compounds -estrone (El) and 17 beta-estradiol (E2)- in human serum. Two isotope dilution mass spectrometry (IDMS) quantification procedures have been used: a classical calibration curve-based method were compared to a recently developed isotope pattern deconvolution (IPD) method. IPD is based on isotopic abundance measurements and multiple linear regression. Validation was performed in terms of intra-assay repeatability (n = 5), inter-assay reproducibility (n=9) and accuracy using spiked steroid-free serum at 5 concentration levels and 3 certified reference materials. Both methodologies meet EMEA requirements yielding recoveries between 79-106% and coefficient of variations of 1.7-8.3% along all experiments. Limits of quantification as low as 5 ng/L were achieved. 40 real samples were analysed for comparison purposes showing a great correlation between calibration and IPD concentration values. Real samples were also quantified by routine immunoassay analysis, which showed a significant proportional bias of 2.55 for E1 and good correlation for E2. While methods were considered suitable for routine or countercheck analysis within the context of hospital's needs, IPD has demonstrated to be faster and cost saving. (C) 2019 Elsevier B.V. All rights reserved.

To gather expert opinion on the conduct of clinical trials that will facilitate regulatory review and approval of appropriate efficacious pharmacological treatments for hand osteoarthritis (OA), which there is currently no approved medication in Europe.