Hälso- och sjukvårdslagen föranstaltar om en kostnadseffektiv och jämlik diagnostik inom den svenska hälso- och sjukvården. Samtidigt ökar efterfrågan på laboratorietest mer än annan medicinsk aktivitet, och utvecklingen leder även till att utbudet av laboratorietest ökar [1]. Vårdens generella resursbrist har lett till ökad betoning på värdeskapande testanvändning globalt [2] med fokus på såväl underanvändning av test (försenar korrekt diagnos och adekvat behandling) som överanvändning (medför överdiagnostik och resursslöseri) [3].Som en följd av denna utveckling har laboratorieverksamheten inom Region Östergötland initierat strategier med syfte att åstadkomma en mer rationell användning av laboratoriemedicinska analyser. Detta har skett genom en aktivare uppföljning av beställningsmönster åtföljd av information och feedback i relation till observerade beställningsmönster. År 2016 initierades s k KRAMA-strategier (KRAMA = Kompetensgruppen för rationell användning av medicinsk diagnostik i alla delar av vårdkedjan) (Figur 1). En viktig ambition var att överge ett passivt testinförande till förmån för ett mer effektivt införande i kombination med aktiv uppföljning av beställningsmönster.

Systematic reviews and meta-analyses have shown that there is little justification for vitamin D supplements to prevent infections, cancer and cardiovascular disease. Despite the limited evidence of effectiveness, the total number of ordered serum 25-hydroxyvitamin D (25(OH)D) tests has increased considerably in recent years. There seems to be an overuse of this test that does not provide meaningful benefit for patients. A passive introduction of new tests leads generally to a slow initiation of value-based diagnostics, as well as overuse and underuse of diagnostic tests. In this study, in Region Östergötland, we applied a »Choosing wisely« model that reversed a rising trend of 25(OH)D tests and reduced the number of unnecessary tests. The findings point to the need for strategic plans for introducing new analyses and approaches to counteract misuse of laboratory diagnostics. We recommend »Choosing wisely« models for the introduction of new analyses to facilitate appropriate laboratory diagnostics and to counteract long-term overuse.

This prospective study investigated growth and skeletal development for 3years after kidney transplantation in pediatric patients, 3.4-15.0years of age. Growth, BMD, bone resorption markers (CTX and TRACP5b), bone formation markers (PINP, ALP, and osteocalcin), PTH, and vitamin D were assessed at start, 3, 12, and 36months after transplantation. Median GFR was 63 (range 37-96) mL/min/1.73m(2) after 3years. The median height SDS increased from -1.7 to -1.1, and median BMI SDS increased from -0.1 to 0.6 over 3years, which shows that transplantation had a favorable outcome on growth. Fat mass increased after transplantation at all time points, whereas lean mass increased after 1year and 3years. Total BMC increased at all time points. No changes were observed for total BMD. Bone resorption markers decreased initially after 3months and remained stable throughout the study, whereas the bone formation markers decreased initially, but successively increased over the study period. In conclusion, this study demonstrates that height SDS and BMI SDS increased, along with the increased formation markers that reveal a positive bone acquisition after kidney transplantation, which was reflected by the significant increase in total body BMC.

Age- and gender-specific reference intervals are pivotal to ensure appropriate interpretation of plasma alkaline phosphatase activities in the lower range Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations of the ALPL gene that mainly express alkaline phosphatase (ALP) in bone and liver. The clinical expression of HPP is highly variable and is classified into six different forms mainly affecting bone and tooth mineralization. The prognosis for each of these HPP forms depends upon the severity of the skeletal disease which reflects the age at presentation. The biochemical hallmark of HPP is low plasma ALP activity (hypophosphatasemia); however, HPP is often misdiagnosed because of low awareness and sometimes absence of age- and gender-specific ALP reference intervals. Children and adolescents have higher ALP levels in comparison with adults. Reliable reference intervals are pivotal for any clinical laboratory test. Harmonized age- and gender-specific plasma ALP reference intervals ought to be used to ensure appropriate interpretation of plasma ALP activities in the lower range.

Objective: To describe an intensive nutrition therapy for hospitalized adolescents and young adults with anorexia nervosa (AN) in terms of body weight, body composition, energy balance and food related anxiety. Method: Twenty-six young females, 16-24 years of age, with AN were invited to participate at admission to a specialized eating disorder unit in Goteborg, Sweden. Intensive nutrition therapy comprised 12 weeks on a structured meal plan. Six meals were served daily, in combination with high-energy liquid nutritional supplements from start. Energy and nutrient intakes, energy expenditure, body composition and food related anxiety were measured during the study. A 3-month follow-up of body weight and food related anxiety was conducted. Results: Twenty-one patients participated. The total daily energy intake was, during the first week of treatment, (mean +/- SD) 3264 +/- 196 kcal (74 kcal/kg), and decreased gradually during treatment to 2622 +/- 331 kcal (49 kcal/kg). Total daily energy expenditure was initially 1568 +/- 149 kcal and increased gradually to 2034 +/- 194 kcal. Patients gained on average 9.8 +/- 2.1 kg and body mass index increased from 15.5 +/- 0.9 to 19.0 +/- 0.9 kg/m(2). Body fat increased from 13 +/- 6% to 26 +/- 6%. Fat free mass remained unchanged, but skeletal muscle mass increased from 16.7 +/- 2.0 to 17.6 +/- 2.4 kg, p = 0.009. Patients food related anxiety decreased significantly during treatment and was still unchanged 3 months later. Conclusion: The presented intensive nutrition therapy with initially high energy and nutrient intakes produced substantial weight gain, increased fat and muscle mass and decreased food related anxiety in AN patients, without any clinical side effects. (C) 2016 Elsevier Ltd. All rights reserved.

Objective: Osteocalcin (OC), an aboundant non-collagenous bone protein, is inversely associated with parameters of glucose metabolism. Interactions between bone tissue and energy metabolism have not been thoroughly investigated during childhood. This study investigated OC, metabolic parameters and anthropometric characteristics in normal weight and overweight/obese children. Methods: This study comprised 108 (46 normal weight/62 overweight/obese) Swedish 2-9 year old children. Anthropometric data, insulin, glucose, glycosylated haemoglobin (HbA1c), HOMA index, vitamin D, adiponectin, total OC, carboxylated OC (cOC) and undercarboxylated OC (ucOC) were analysed. Results: No difference was found for total OC between the normal and overweight/obese groups, with a mean (+/- SD) value of 82.6 ( +/- 2.8) ng/mL and 77.0 ( +/- 2.4) ng/mL, (P = 0.11), respectively. Overweight children had lower cOC levels, mean 69.1 ( +/- 2.2) ng/mL, vs. normal weight children, mean 75.6 ( +/- 2.5) ng/mL (P = 0.03). The mean ucOC levels of 7.9 ( +/- 0.4) ng/mL in overweight children did not differ vs. normal weight children, mean level 7.0 (+/- 0.4) ng/mL, (P = 0.067). None of the three OC forms correlated with any of the measured parameters. Conclusions: The cOC levels were lower in overweight children. There was no correlation between the three OC forms and any of the measured anthropometric or metabolic parameters. OC has been suggested to have a possible metabolic role, but in general the current study in prepubertal children does not support the hypothesis of an association between OC and a positive metabolic profile. (C) 2016 Elsevier Inc. All rights reserved.

Bone is a biological composite material comprised primarily of collagen type I and mineral crystals of calcium and phosphate in the form of hydroxyapatite (HA), which together provide its mechanical properties. Bone alkaline phosphatase (ALP), produced by osteoblasts, plays a pivotal role in the mineralization process. Affinity contacts between collagen, mainly type II, and the crown domain of various ALP isozymes were reported in a few in vitro studies in the 1980s and 1990s, but have not attracted much attention since, although such interactions may have important implications for the bone mineralization process. The objective of this study was to investigate the binding properties of human collagen type I to human bone ALP, including the two bone ALP isoforms B1 and B2. ALP from human liver, human placenta and E. coli were also studied. A surface plasmon resonance-based analysis, supported by electrophoresis and blotting, showed that bone ALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. Further, the B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform. Human bone and liver ALP (with identical amino acid composition) displayed pronounced differences in binding, revealing that post-translational glycosylation properties govern these interactions to a large extent. In conclusion, this study presents the first evidence that glycosylation differences in human ALPs are of crucial importance for protein–protein interactions with collagen type I, although the presence of the ALP crown domain may also be necessary. Different binding affinities among the bone ALP isoforms may influence the mineral-collagen interface, mineralization kinetics, and degree of bone matrix mineralization, which are important factors determining the material properties of bone.

Background: Renal osteodystrophy encompasses the bone histologic abnormalities seen in patients with chronic kidney disease (CKD). The bone-specific alkaline phosphatase (bALP) isoform B1x is exclusively found in serum of some patients with CKD. Study Design: The aim of this cross-sectional diagnostic test study was to examine the relationship between serum bALP isoform activity and histomorphometric parameters of bone in patients with CKD receiving maintenance hemodialysis. Settings and Participants: Anterior iliac crest bone biopsy samples from 40 patients with CKD were selected on the basis of bone turnover for histomorphometric analysis. There were samples from 20 patients with low and 20 with non-low bone turnover. Index Test: In serum, bALP, bALP isoforms (B/I, B1x, B1, and B2), and parathyroid hormone (PTH) were measured. Reference Test: Low bone turnover was defined by mineral apposition rate, 0.36 mu m/d. Non-low bone turnover was defined by mineral apposition rate greater than= 0.36 mu m/d. Other Measurements: PTH. Results: B1x was found in 21 patients (53%) who had lower median levels of bALP, 18.6 versus 46.9 U/L; B/I, 0.10 versus 0.22 mu kat/L; B1, 0.40 versus 0.88 mu kat/L; B2, 1.21 versus 2.66 mu kat/L; and PTH, 49 versus 287 pg/mL, compared with patients without B1x (P less than 0.001). 13 patients (65%) with low bone turnover and 8 patients (40%) with non-low bone turnover (P less than 0.2) had detectable B1x. B1x correlated inversely with histomorphometric parameters of bone turnover. Receiver operating characteristic curves showed that B1x can be used for the diagnosis of low bone turnover (area under the curve [AUC], 0.83), whereas bALP (AUC, 0.89) and PTH (AUC, 0.85) are useful for the diagnosis of non-low bone turnover. Limitations: Small number of study participants. Requirement of high-performance liquid chromatography methods for measurement of B1x. Conclusions: B1x, PTH, and bALP have similar diagnostic accuracy in distinguishing low from non-low bone turnover. The presence of B1x is diagnostic of low bone turnover, whereas elevated bALP and PTH levels are useful for the diagnosis of non-low bone turnover.

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BACKGROUND/AIMS: Vitamin D deficiency and elevated serum fibroblast growth factor-23 (FGF23) levels are hallmark features and surrogate markers of adverse clinical outcomes in patients with chronic kidney disease (CKD). Convection of molecules over the dialysis membrane during online hemodiafiltration (ol-HDF) increases the removal of larger waste molecules compared with traditional high-flux hemodialysis (HD). The primary aim of this study was to explore the long-term impact of ol-HDF on serum 25(OH)D and FGF23.

METHOD: An observational, prospective, noncomparator study including 35 patients who were switched from HD to ol-HDF. Serum 25(OH)D and FGF23 were measured at baseline (i.e., time of switch to ol-HDF) and at 6, 12, and 24 months.

RESULTS: At follow-up time points, there was a significant reduction in serum 25(OH)D compared with baseline (p < 0.0001) whereas FGF23 was unaltered (p > 0.05). The decrease in 25(OH)D was more prominent in individuals with higher baseline 25(OH)D levels.

CONCLUSION: Ol-HDF may lower systemic 25(OH)D levels by convective mechanisms although the clinical significance remains unknown. Further controlled studies are warranted to replicate these findings in larger patient cohorts.

Purpose This study investigated the relationship between seasonal variations in 25-hydroxyvitamin D (25(OH) D) levels and growth in prepubertal children during both the pretreatment year and the first year of GH treatment. Methods The study included 249 short prepubertal children with a broad range of GH secretion, GH(max) during a 24 h profile median 23; range 1-127 mU/L, 191 boys (mean age +/- SD, 8.6 +/- 2.6 years), 58 girls (7.5 +/- 1.9 years) receiving GH treatment (mean 43 mu g/kg/day; range 17-99 mu g/kg/day). Serum 25(OH) D was measured using an automated IDS-iSYS immunoassay. Results 25(OH) D levels showed seasonal variation, and decreased significantly during GH treatment. 25(OH) D levels at start and first year reduction in 25(OH) D, correlated (-) with the first year growth response during treatment. The degree of GH secretion capacity within our study population of mainly non-GH deficient children and 25(OH) D sufficient (67 +/- 29 nmol/L) had no influence on 25(OH) D levels. Growth during GH treatment were independent of seasonal variations in 25(OH) D. Multiple regression analysis showed that 25(OH) D levels at treatment start, together with auxological data and IGF-binding protein-3(SDS), explained 61 % of the variation in first year gain in height(SDS). Conclusion 25(OH) D levels were associated with first year growth response to GH and may be a useful contribution to future growth prediction models.