BackgroundChronic kidney disease (CKD) is associated with disturbances in mineral and bone metabolism, increasing fracture risk, particularly in advanced stages. Bone turnover markers (BTMs) such as bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase 5b (TRACP5b), as well as collagen-derived markers including intact form of procollagen type I amino-terminal propeptide (iPINP) and beta-cross-linked C-terminal telopeptide of type I collagen (beta-CTX-I), are recommended to assess bone turnover. Although some BTMs are considered stable and independent of renal function, their behavior during dialysis sessions remains unclear.MethodsTo assess the impact of dialysis techniques and membrane types, serum samples were collected pre- and post-dialysis. BTM concentrations were analyzed using nonparametric statistics, and the clinical relevance of the observed changes was evaluated using the least significant change (LSC) thresholds.ResultsBALP and TRACP5b showed minor fluctuations post-dialysis, with changes remaining below their clinical significance thresholds. iPINP also showed limited variability. In contrast, beta-CTX-I decreased significantly after hemodialysis, especially using high-permeability membranes, with changes exceeding the LSC threshold.ConclusionThese findings suggest that BALP, TRACP5b, and PINP demonstrate robustness as BTMs in CKD patients undergoing dialysis. However, beta-CTX-I is markedly affected by dialysis parameters and should be interpreted cautiously in this context.

Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has 5 potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303, and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl^+/− expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and liquid chromatography with tandem mass spectrometry. The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all 5 sites of TNALP, as well as core fucosylation on 4 out of 5 sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.

ontext: Anemia and decreasing levels of hemoglobin (Hb) have previously been linked to increased fracture risk, but the added value to FRAX, the most utilized fracture prediction tool worldwide, is unknown.

Objective: To investigate the association between anemia, Hb levels, bone microstructure, and risk of incident fracture and to evaluate whether Hb levels improve fracture risk prediction in addition to FRAX clinical risk factors (CRFs).

Methods: A total of 2778 community-dwelling women, aged 75-80 years, and part of a prospective population-based cohort study in Sweden were included. At baseline, information on anthropometrics, CRFs, and falls was gathered, blood samples were collected, and skeletal characteristics were investigated using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. At the end of follow-up, incident fractures were retrieved from a regional x-ray archive.

Results: The median follow-up time was 6.4 years. Low Hb was associated with worse total hip and femoral neck bone mineral density (BMD), and lower tibia cortical and total volumetric BMD, and anemia was associated with increased risk of major osteoporotic fracture (MOF; hazard ratio 2.04; 95% CI 1.58-2.64). Similar results were obtained for hip fracture and any fracture, also when adjusting for CRFs. The ratio between 10-year fracture probabilities of MOF assessed in models with Hb levels included and not included ranged from 1.2 to 0.7 at the 10th and 90th percentile of Hb, respectively.

Conclusion: Anemia and decreasing levels of Hb are associated with lower cortical BMD and incident fracture in older women. Considering Hb levels may improve the clinical evaluation of patients with osteoporosis and the assessment of fracture risk.

Aim To determine whether adolescents born before 28 gestational weeks have an increased risk for renal impairment. Methods Swedish infants, born before 28 gestational weeks in 2001 and 2002, were identified from a local register. A total of 16 children, 12 females and 4 males, were examined at 16-17 years of age with Cr-51-EDTA clearance. A comparison group (n = 26) was used. Results Most study participants (n = 13) had normal blood pressure; one individual had hypertension stage 1. All study participants had results within the reference interval for ionised calcium, parathyroid hormone, intact fibroblast growth factor-23 and for urinary albumin-to-creatinine ratio. Four out of 16 participants (25%) had a Cr-51-EDTA clearance less than 90 ml/min/1.73 m(2), indicating a reduced kidney function. Measured Cr-51-EDTA clearance values were significantly lower in the study group than in the comparison group (p = 0.0012). Five study participants (31%) were referred for further investigations. Conclusion Swedish children born before 28 gestational weeks have an increased risk of renal impairment later in life, suggesting that the kidney function in these individuals should be assessed, at least once, during adolescence.

Objective: The aim of this prospective study was to investigate the potential influence of the fat mass and obesity-associated gene (FTO), SNP rs9939609, on body mass index (BMI) and body composition in women with anorexia nervosa (AN) undergoing intensive nutrition therapy. Method: Twenty-five female patients with AN (20.1 +/- 2.3 years; BMI, 15.5 +/- 0.9 kg/m(2)) were included for 12 weeks of treatment with a high-energy diet. FTO was genotyped and body composition parameters were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography at baseline and after 12 weeks. Results: The distribution of the different FTO genotypes were as follows: AA, 24%; TA, 48%; and TT, 28%. Patients gained a median of 9.8 kg (range, 5.5-17.0 kg) and BMI increased to 19.0 +/- 0.9 kg/m(2). The increase in BMI, fat mass, and the quotient fat/muscle area was significant for the TT and TA genotype groups. Total lean mass was stable in all genotype groups. We could not demonstrate any difference among the 3 FTO genotypes related to the increases in BMI during nutrition therapy when the additive, dominant, and recessive models of inheritance were applied. Conclusions: Irrespective of the FTO genotype, there was no difference in weight response during nutrition therapy. Hence, in this small study there was limited support for individualized nutrition therapy for AN based on FTO genotype.

The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. Introduction The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. Methods A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75-80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. Results Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80-3.18] and hip fracture 2.96 [1.62-5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5-1.9 in a 75-year-old woman with slow TUG (> 12 s). Conclusion The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women.

Because prevalent vertebral fracture (VF) is a strong predictor of future fractures, they are important to identify in clinical practice as osteoporosis medications are effective and can be used to reduce fracture risk in postmenopausal women with VF. Lateral spine imaging (LSI) with dual-energy X-ray absorptiometry (DXA) can be used to diagnose VFs accurately but is not widespread in clinical practice. The prognostic value of grade 1 (20% to 25% compression) VFs diagnosed by LSI with DXA has been insufficiently studied. The aim of this study was to determine if grade 1 VF is associated with incident fracture in older women. Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a population-based study of 3028 older women from Gothenburg, Sweden. Included women were 75 to 80 years of age at baseline, answered questionnaires, and were scanned with DXA (Discovery A, Hologic, Waltham, MA, USA). LSI was used to diagnose VFs, which were classified using the Genant semiquantitative method. Cox regression models were used to estimate the association between VFs at baseline and X-ray-verified incident fractures, with adjustment for confounders. Women with a grade 1 VF (n = 264) or a grade 2-3 VF (n = 349) were compared with women without any fracture (n = 1482). During 3.6 years (median, interquartile range [IQR] 1.5 years) of follow-up, 260 women had any incident fracture and 213 a major osteoporotic fracture (MOF). Women with only grade 1 VF had increased risk of any fracture (hazard ratio [HR] = 1.67; 95% confidence interval [CI] 1.18-2.36) and MOF (HR = 1.86; 95% CI 1.28-2.72). For MOF, this association remained after adjustment for clinical risk factors and femoral neck bone mineral density (BMD). In conclusion, grade 1 VFs were associated with incident MOF, also after adjustment for clinical risk factors and BMD, indicating that all VF identified by DXA should be considered in the evaluation of fracture risk in older women. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..

Purpose of Review To summarize the last 10 years of literature regarding the effects of whole-body vibration (WBV) on bone in children, and if WBV results in increased bone acquisition. Recent Findings WBV intervention appears to be a safe intervention with beneficial effects on bone mass in some diseases and syndromes, but there is still low evidence for WBV in clinical practice. The positive effects on muscle strength, balance, and walking speed are more conclusive. One of the takeaways of this review is that well-trained individuals may not further improve bone mass with WBV; thus, interventions are more beneficial in pediatric individuals with Down syndrome or severe motor disabilities with low bone mass and reduced activity levels. WBV appears to be a safe non-pharmacological anabolic approach to increase bone mass in some pediatric populations; however, longer (> 6 months) and larger prospective studies are needed to elucidate the efficacy of WBV on bone health in young individuals.

PURPOSE OF REVIEW: In chronic kidney disease (CKD), disturbance of several metabolic regulatory mechanisms cause premature ageing, accelerated cardiovascular disease (CVD), and mortality. Single-target interventions have repeatedly failed to improve the prognosis for CKD patients. Epigenetic interventions have the potential to modulate several pathogenetic processes simultaneously. Alkaline phosphatase (ALP) is a robust predictor of CVD and all-cause mortality and implicated in pathogenic processes associated with CVD in CKD.

RECENT FINDINGS: In experimental studies, epigenetic modulation of ALP by microRNAs or bromodomain and extraterminal (BET) protein inhibition has shown promising results for the treatment of CVD and other chronic metabolic diseases. The BET inhibitor apabetalone is currently being evaluated for cardiovascular risk reduction in a phase III clinical study in high-risk CVD patients, including patients with CKD (ClinicalTrials.gov Identifier: NCT02586155). Phase II studies demonstrate an ALP-lowering potential of apabetalone, which was associated with improved cardiovascular and renal outcomes.

SUMMARY: ALP is a predictor of CVD and mortality in CKD. Epigenetic modulation of ALP has the potential to affect several pathogenetic processes in CKD and thereby improve cardiovascular outcome.

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.