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Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment. In this multicenter study, we enrolled 23 adult patients with a diagnosis of HPP and compared them with 46 osteoporotic subjects previously treated with zoledronic acid or denosumab. BTMs such as CTX, N-terminal propeptide of type I procollagen (P1NP), total ALP, and bone ALP (bALP) were measured, and ratios between BTMs were also calculated. Considering that the control group included only females, in the primary analysis we compared their characteristics with that of the 16 female patients with HPP. Both individual BTMs (CTX and P1NP) and 4 BTM ratios (ALP/P1NP, bALP/P1NP, ALP/CTX, and bALP/CTX) showed satisfactory discriminatory power, outperforming ALP alone. P1NP, in particular, had an area under the curve (AUC) of 0.962 with a cut-off of 32 μg/L, while as for the BTMs ratios, the ALP/P1NP ratio had an AUC of 0.964 with a cut-off of 1.114. Similar results were confirmed when including male HPP patients, when adjusting for age and sex, and finally when performing a sensitivity analysis only in patients with ALP less than or equal to 32 U/L (ie, the median of the distribution of the entire population). In cases of low ALP and bone fragility, BTM and their ratios could help distinguish HPP patients from osteoporotic individuals treated with antiresorptive drugs, aiding in accurate diagnosis and reducing the risk of inappropriate treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context: Type 2 diabetes (T2DM) is associated with a higher intestinal expression of the glucose transporters sodium/glucose cotransporter 1 (SGLT-1) and glucose transporter 2 (GLUT-2). It is currently unsettled whether prediabetes conditions characterized by postprandial hyperglycemia, such as impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) with 1-hour postload glucose ≥155 mg/dL (8.6 mmol/L) (NGT-1h-high) are associated with increased expression of these glucose carriers in the intestine., Objective: We evaluated whether duodenal abundance of SGLT-1 and GLUT-2 is augmented in subjects with IGT and NGT-1h-high, in comparison with subjects with NGT and 1-hour postload glucose ˂155 mg/dL (NGT-1h-low)., Design: Cross-sectional., Patients: A total of 54 individuals underwent an upper gastrointestinal endoscopy., Main Outcome Measures: Duodenal SGLT-1 and GLUT-2 protein and messenger RNA levels were assessed by Western blot and reverse transcription polymerase chain reaction, respectively., Results: Of the 54 subjects examined, 18 had NGT-1h-low, 12 had NGT-1h-high, 12 had IGT, and 12 had T2DM. Duodenal SGLT-1 protein and messenger RNA levels were significantly higher in individuals with NGT-1h-high, IGT, or T2DM in comparison with NGT-1h-low subjects. GLUT-2 abundance was higher in individuals with T2DM in comparison with NGT-1h-low subjects; no substantial increase in GLUT-2 expression was observed in NGT-1h-high or IGT individuals. Univariate correlations showed that duodenal SGLT-1 abundance was positively correlated with 1-hour postload plasma glucose levels (r = 0.44; P = 0.003) but not with fasting or 2-hour postload glucose levels., Conclusions: Duodenal SGLT-1 expression is increased in individuals with 1-hour postload hyperglycemia or IGT, as well as in subjects with T2DM, and it positively correlates with early postload glucose excursion., (Copyright © 2017 Endocrine Society)