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Background: Hypophosphatasia (HPP) is an autosomal recessive or dominate disease affecting bone mineralization, and adults with HPP are in risk to develop metatarsal stress fractures and femoral pseudofractures. Given to the scarce data on the bone quality and its association to the fracture risk in adults with HPP, this study aimed to evaluate bone turnover, bone strength and structure in adults with HPP., Methods: In this cross-sectional study, we included 14 adults with genetically verified HPP and 14 sex-, age-, BMI-, and menopausal status-matched reference individuals. We analyzed bone turnover markers, and measured bone material strength index (BMSi) by impact microindentation. Bone geometry, volumetric density and bone microarchitecture as well as failure load at the distal radius and tibia were evaluated using a second-generation high-resolution peripheral quantitative computed tomography system., Results: Bone turnover markers did not differ between patients with HPP and reference individuals. BMSi did not differ between the groups (67.90 [63.75-76.00] vs 65.45 [58.43-69.55], p = 0.149). Parameters of bone geometry and volumetric density did not differ between adults with HPP and the reference group. Patients with HPP had a tendency toward higher trabecular separation (0.664 [0.613-0.724] mm vs 0.620 [0.578-0.659] mm, p = 0.054) and inhomogeneity of trabecular network (0.253 [0.235-0.283] mm vs 0.229 [0.208-0.252] mm, p = 0.056) as well as lower trabecular bone volume fraction (18.8 [16.4-22.7] % vs 22.8 [20.6-24.7] %, p = 0.054) at the distal radius. In addition, compound heterozygous adults with HPP had a significantly higher cortical porosity at the distal radius than reference individuals (1.5 [0.9-2.2] % vs 0.7 [0.6-0.7] %, p = 0.041)., Conclusions: BMSi is not reduced in adults with HPP. Increased cortical porosity may contribute to the occurrence of femoral pseudofractures in compound heterozygous adults with HPP. However, further studies investigating larger cohorts of adults with HPP using methods of bone histomorphometry are recommended to adequately assess the bone quality in adults with HPP., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Management of osteoporosis given reduced renal function is one of the largest challenges in the bone clinic., Objectives: Identify the cut-off for renal function below which there would be no overall BMD benefit associated with bisphosphonate use. Track safety outcomes resulting in hospital encounters., Methods: Population-based, observational register-linked study of BMD trajectories in adults from the island of Funen (pop 465,000) as a function of estimated creatinine clearance (CKD-epi), treatment and adherence to oBP. One laboratory performed all the biochemical analyses for the area while all DXA scans were in a central facility. For inclusion, patients were required to have both a DXA scan and an eGFR measurement (CKD-EPI) within 1 year prior to their study index date. Medication Possession Ratio (MPR) was calculated from national data., Results: Out of 6176 incident BP users, 1789 had eGFR and DXA measurements at appropriate timepoints for the planned analysis, while this was the case for 3908 of 29,336 non-users. Users of oBPs exhibited progressively smaller gains in BMD with decreasing renal function. However, for CKD stage 3A and better, the annual change in BMD was significantly more positive than in the non-user group at similar levels of renal function. In non-users, the average annual change in BMD was negative but largely unaffected by renal function down to stage 3B. There were no new cases of acute renal injury, glomerulonephritis or dialysis. The rate of new kidney transplantation was zero in non-users and 0.26 per 1000 PY in the BP user population. Hypocalcaemia encounters did not differ significantly from that seen in non-users., Conclusions: The BMD changes observed in real-world users of oBP in this population based single-clinic are consistent with those observed in the original RCTs of alendronate. We noted a gradual decrease in the absolute gains in BMD in oBP users with decreasing renal function though there was no significant interaction - largely explained by low numbers of treated patients with poor renal function - between CKD stage and adherence driven BMD change. There were no cases of acute renal injury resulting in hospital encounters. More data is needed on the efficacy and safety of bisphosphonates in CKD stage 3B to 5 and prescribers should reconsider the low use of DXA in patients with renal function impairment now that a wider range of treatment options are available., Competing Interests: Declaration of competing interest BA: Consulting and speakers fees Amgen, UCB, Kyowa-Kirin UK. Institutional research contracts UCB and Novartis. DPA: Grants and other support from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department and open for external participants. APH: Consulting and speakers fees Amgen, UCB. Institutional research contracts Kyowa-Kirin UK and Shire. CDS, MTE, MN, KHR: None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: A diagnostic gap exists in the current dual photon X-ray absorptiometry (DXA) based diagnostic approach to osteoporosis. Other diagnostic devices have been developed, but no comprehensive review concerning the applicability of these diagnostic devices for population-based screening have been performed., Material and Methods: A systematic review of Embase, Medline and the Cochrane Central Register for Controlled Trials was performed for population-based studies that focused on technical methods that could either indicate bone mineral density (BMD) by DXA, substitute for DXA in prediction of fracture risk, or that could have an incremental value in fracture prediction in addition to DXA. Quality of included studies was rated by QUADAS 2., Results: Many other technical devices have been tested in a population-based setting. Five studies aiming to indicate BMD and 17 studies aiming to predict fractures were found. Overall, the latter studies had higher methodological quality. The highest number of studies was found for quantitative ultrasound (QUS). The ability to indicate BMD or predict fractures was moderate to minor for all examined devices, using reported area under the curve (AUC) of Receiver Operating Characteristic curves values as standard., Conclusions: Of the methods assessed, only QUS appears capable of perhaps replacing DXA as standalone examination in the future whilst radiographic absorptiometry could provide important information in areas with scarcity of DXA. QUS may be of added value even after DXA has been performed. Evaluation of proposed cutoff-values from population-based studies in separate population-based cohorts is still lacking for most examination devices., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To compare the power of FRAX® without bone mineral density (BMD) and simpler screening tools (OST, ORAI, OSIRIS, SCORE and age alone) in predicting fractures., Methods: This study was a prospective, population-based study performed in Denmark comprising 3614 women aged 40-90 years, who returned a questionnaire concerning items on risk factors for osteoporosis. Fracture risk was calculated using the different screening tools (FRAX®, OST, ORAI, OSIRIS and SCORE) for each woman. The women were followed using the Danish National Register registering new major osteoporotic fractures during 3 years, counting only the first fracture per person. Area under the receiver operating characteristic curve (ROC) and statistics and Harrell's index were calculated. Agreement between the tools was calculated by kappa statistics., Results: A total of 4% of the women experienced a new major osteoporotic fracture during the follow-up period. There were no differences in the area under the curve (AUC) values between FRAX® and the simpler tools; AUC values between 0.703 and 0.722 (p = 0.86). Also, Harrell's C values were very similar between the tools. Agreement between the tools was modest., Conclusion: During 3 years follow-up FRAX® did not perform better in the fracture risk prediction compared with simpler tools such as OST, ORAI, OSIRIS, SCORE or age alone in a screening scenario where BMD was not measured. These findings suggest that simpler models based on fewer risk factors, which would be easier to use in clinical practice by the GP or the patient herself, could just as well as FRAX® be used to identify women with increased risk of fracture., Summary: Comparison of FRAX® and simpler screening tools (OST, ORAI, OSIRIS, SCORE) in predicting fractures indicate that FRAX® did not perform better in fracture risk prediction compared with the simpler tools or even age alone in a screening scenario without bone mineral density assessment., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

A BsmI restriction enzyme polymorphism in the vitamin D receptor (VDR) gene has been reported to be associated with bone mineral density (BMD) and bone turnover. However, findings in other studies suggest the presence of considerable interaction by race, body size, and environmental factors. Therefore, we VDR BsmI genotyped 200 healthy perimenopausal Danish white women (mean age 50.8 years, mean calcium intake 900 mg/day) in a comprehensive, longitudinal, community-based population study. Bone loss was assessed by dual-energy X-ray absorptiometry (DXA) using cross-calibrated Hologic QDR-1000W and QDR-2000 densitometers, with a mean follow-up period of 4 years (range 1-5 years). Despite a distribution of genotypes similar to that of other white populations (28% bb, 49% Bb, 23% BB), VDR genotypes were not associated with lumbar or femoral baseline BMD, subsequent bone loss rates, or biochemical markers of bone metabolism (bone-specific alkaline phosphatase, urinary hydroxyproline, and serum osteocalcin). Controlling for body size, calcium intake, and serum levels of 25-hydroxyvitamin D3 [25(OH)D3] did not alter this finding. The possible existence of a threshold effect was subsequently investigated by restricting analysis to women with low serum 25(OH)D3 levels or low calcium intake. VDR BsmI genotypes showed no significant impact on bone density or bone loss in healthy Danish early postmenopausal women, even when allowance was made for calcium intake, serum 25(OH)D3, and body size.