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      Added Value of Impact Microindentation in the Evaluation of Bone Fragility: A Systematic Review of the Literature

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          Abstract

          The current gold standard for the diagnosis of osteoporosis and the prediction of fracture risk is the measurement of bone mineral density (BMD) using dual energy x-ray absorptiometry (DXA). A low BMD is clearly associated with increased fracture risk, but BMD is not the only determinant of bone strength, particularly in secondary osteoporosis and metabolic bone disorders in which components other than BMD are affected and DXA often underestimates true fracture risk. Material properties of bone which significantly contribute to bone strength have become evaluable in vivo with the impact microindentation (IMI) technique using the OsteoProbe® device. The question arises whether this new tool is of added value in the evaluation of bone fragility. To this effect, we conducted a systematic review of all clinical studies using IMI in vivo in humans also addressing practical aspects of the technique and differences in study design, which may impact outcome. Search data generated 38 studies showing that IMI can identify patients with primary osteoporosis and fractures, patients with secondary osteoporosis due to various underlying systemic disorders, and scarce longitudinal data also show that this tool can detect changes in bone material strength index (BMSi), following bone-modifying therapy including use of corticosteroids. However, this main outcome parameter was not always concordant between studies. This systematic review also identified a number of factors that impact on BMSi outcome. These include subject- and disease-related factors such as the relationship between BMSi and age, geographical region and the presence of fractures, and technique- and operator-related factors. Taken together, findings from this systematic review confirm the added value of IMI for the evaluation and follow-up of elements of bone fragility, particularly in secondary osteoporosis. Notwithstanding, the high variability of BMSi outcome between studies calls for age-dependent reference values, and for the harmonization of study protocols. Prospective multicenter trials using standard operating procedures are required to establish the value of IMI in the prediction of future fracture risk, before this technique is introduced in routine clinical practice.

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          In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography.

          Assessment of trabecular microarchitecture may enhance the prediction of fracture risk and improve monitoring of treatment response. A new high-resolution peripheral quantitative computed tomography (HR-pQCT) system permits in vivo assessment of trabecular architecture and volumetric bone mineral density (BMD) at the distal radius and tibia with a voxel size of 82 microm3. We determined the short-term reproducibility of this device by measuring 15 healthy volunteers three times each. We compared HR-pQCT measurements in 108 healthy premenopausal, 113 postmenopausal osteopenic, and 35 postmenopausal osteoporotic women. Furthermore, we compared values in postmenopausal osteopenic women with (n = 35) and without previous fracture history (n = 78). We conducted a cross-sectional study in a private clinical research center. We took HR-pQCT measurements of the radius and tibia. Femoral neck and spine BMD were measured in postmenopausal women by dual-energy x-ray absorptiometry. Precision of HR-pQCT measurements was 0.7-1.5% for total, trabecular, and cortical densities and 2.5-4.4% for trabecular architecture. Postmenopausal women had lower density, trabecular number, and cortical thickness than premenopausal women (P < 0.001) at both radius and tibia. Osteoporotic women had lower density, cortical thickness, and increased trabecular separation than osteopenic women (P < 0.01) at both sites. Furthermore, although spine and hip BMD were similar, fractured osteopenic women had lower trabecular density and more heterogeneous trabecular distribution (P < 0.02) at the radius compared with unfractured osteopenic women. HR-pQCT appears promising to assess bone density and microarchitecture at peripheral sites in terms of reproducibility and ability to detect age- and disease-related changes.
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            In vivo assessment of bone quality in postmenopausal women with type 2 diabetes.

            Although patients with type 2 diabetes (T2D) are at significant risk for well-recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to nondiabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone "quality"). Thus, we performed in vivo microindentation testing of the tibia to directly measure BMS in 60 postmenopausal women (age range, 50-80 years) including 30 patients diagnosed with T2D for >10 years and 30 age-matched, nondiabetic controls. Regional BMD was measured by dual-energy X-ray absorptiometry (DXA); cortical and trabecular bone microarchitecture was assessed from high-resolution peripheral quantitative computed tomography (HRpQCT) images of the distal radius and tibia. Compared to controls, T2D patients had significantly lower BMS: unadjusted (-11.7%; p<0.001); following adjustment for body mass index (BMI) (-10.5%; p<0.001); and following additional adjustment for age, hypertension, nephropathy, neuropathy, retinopathy, and vascular disease (-9.2%; p=0.022). By contrast, after adjustment for confounding by BMI, T2D patients had bone microarchitecture and BMD that were not significantly different than controls; however, radial cortical porosity tended to be higher in the T2D patients. In addition, patients with T2D had significantly reduced serum markers of bone turnover (all p<0.001) compared to controls. Of note, in patients with T2D, the average glycated hemoglobin level over the previous 10 years was negatively correlated with BMS (r=-0.41; p=0.026). In conclusion, these findings represent the first demonstration of compromised BMS in patients with T2D. Furthermore, our results confirm previous studies demonstrating low bone turnover in patients with T2D and highlight the potential detrimental effects of prolonged hyperglycemia on bone quality. Thus, the skeleton needs to be recognized as another important target tissue subject to diabetic complications. © 2014 American Society for Bone and Mineral Research. © 2014 American Society for Bone and Mineral Research.
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              Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus

              The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                07 February 2020
                2020
                : 11
                : 15
                Affiliations
                Department of Medicine, Division of Endocrinology and Center for Bone Quality, Leiden University Medical Center , Leiden, Netherlands
                Author notes

                Edited by: Teun J. De Vries, VU University Amsterdam, Netherlands

                Reviewed by: Graziana Colaianni, University of Bari Aldo Moro, Italy; Connie M. Weaver, Purdue University, United States

                *Correspondence: Natasha M. Appelman-Dijkstra n.m.appelman-dijkstra@ 123456lumc.nl

                This article was submitted to Bone Research, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2020.00015
                7020781
                32117052
                69016521-2725-4c25-be7c-1c0d4d4051fa
                Copyright © 2020 Schoeb, Hamdy, Malgo, Winter and Appelman-Dijkstra.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 August 2019
                : 09 January 2020
                Page count
                Figures: 2, Tables: 6, Equations: 0, References: 82, Pages: 18, Words: 14295
                Categories
                Endocrinology
                Systematic Review

                Endocrinology & Diabetes
                fracture risk,osteoporosis primary and secondary,rare bone diseases,bone quality,bone material strength index (bmsi),osteoprobe,bone mineral density,dual energy x-ray absorptiometry (dxa)

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