Lower estimated bone strength and impaired bone microarchitecture in children with type 1 diabetes

IntroductionPatients with type 1 diabetes has an increased risk of fracture. We wished to evaluate estimated bone strength in children and adolescents with type 1 diabetes and assess peripheral bone geometry, volumetric bone mineral density (vBMD) and microarchitecture.Research design and methodsIn a cross-sectional study, high-resolution peripheral quantitative CT (HR-pQCT) was performed of the radius and tibia in 84 children with type 1 diabetes and 55 healthy sibling controls. Estimated bone strength was assessed using a microfinite element analysis solver. Multivariate regression analyses were performed adjusting for age, sex, height and body mass index.ResultsThe median age was 13.0 years in the diabetes group vs 11.5 years in healthy sibling controls. The median (range) diabetes duration was 4.2 (0.4−15.9) years; median (range) latest year Hb1Ac was 7.8 (5.9−11.8) % (61.8 (41−106) mmol/mol). In adjusted analyses, patients with type 1 diabetes had reduced estimated bone strength in both radius, β −390.6 (−621.2 to −159.9) N, p=0.001, and tibia, β −891.9 (−1321 to −462.9) N, p<0.001. In the radius and tibia, children with type 1 diabetes had reduced cortical area, trabecular vBMD, trabecular number and trabecular bone volume fraction and increased trabecular inhomogeneity, adjusted p<0.05 for all. Latest year HbA1c was negatively correlated with bone microarchitecture (radius and tibia), trabecular vBMD and estimated bone strength (tibia).ConclusionChildren with type 1 diabetes had reduced estimated bone strength. This reduced bone strength could partly be explained by reduced trabecular bone mineral density, adverse microarchitecture and reduced cortical area. We also found increasing latest year HbA1c to be associated with several adverse changes in bone parameters. HR-pQCT holds potential to identify early adverse bone changes and to explain the increased fracture risk in young patients with type 1 diabetes.

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DXA parameters, Trabecular Bone Score (TBS) and Bone Mineral Density (BMD), in fracture risk prediction in endocrine-mediated secondary osteoporosis

Endocrine ◽

10.1007/s12020-021-02806-x ◽

2021 ◽

Author(s):

Enisa Shevroja ◽

Francesco Pio Cafarelli ◽

Giuseppe Guglielmi ◽

Didier Hans

Keyword(s):

Bone Mineral Density ◽

Trabecular Bone ◽

Bone Mineral ◽

Trabecular Bone Score ◽

Bone Microarchitecture ◽

Fragility Fractures ◽

Endocrine Disorders ◽

Mineral Density ◽

Increased Risk

AbstractOsteoporosis, a disease characterized by low bone mass and alterations of bone microarchitecture, leading to an increased risk for fragility fractures and, eventually, to fracture; is associated with an excess of mortality, a decrease in quality of life, and co-morbidities. Bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA), has been the gold standard for the diagnosis of osteoporosis. Trabecular bone score (TBS), a textural analysis of the lumbar spine DXA images, is an index of bone microarchitecture. TBS has been robustly shown to predict fractures independently of BMD. In this review, while reporting also results on BMD, we mainly focus on the TBS role in the assessment of bone health in endocrine disorders known to be reflected in bone.

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Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s2175-97902017000400060 ◽

2018 ◽

Vol 53 (4) ◽

Author(s):

Melina Bezerra Loureiro ◽

Marcela Abbott Galvão Ururahy ◽

Karla Simone Costa de Souza ◽

Yonara Monique da Costa Oliveira ◽

Heglayne Pereira Vital da Silva ◽

...

Keyword(s):

Diabetes Mellitus ◽

Bone Mineral Density ◽

Type 1 Diabetes ◽

Glycemic Control ◽

Type 1 Diabetes Mellitus ◽

Bone Mineral ◽

Gene Polymorphisms ◽

Lower Bone Mineral Density ◽

Mineral Density

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Bone Mineral Density and Type 1 Diabetes in Children and Adolescents: A Meta-analysis

10.2337/figshare.14618409 ◽

2021 ◽

Author(s):

Phoebe Loxton ◽

Kruthika Narayan ◽

Craig F Munns ◽

Maria E Craig

Keyword(s):

Bone Mineral Density ◽

Type 1 Diabetes ◽

Lumbar Spine ◽

Bone Mineral ◽

Meta Analysis ◽

Inclusion Criteria ◽

Mineral Density ◽

Multiple Modalities ◽

Meta Regression

Background There is substantial evidence that adults with type 1 diabetes have reduced bone mineral density (BMD), however findings in youth are inconsistent. Purpose Systematic review and meta-analysis of BMD in youth with type 1 diabetes using multiple modalities: dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and/or quantitative ultrasound (QUS). Data Sources PubMed, Embase, Scopus and Web of Science from 01/01/1990 to 31/12/2020, limited to humans, without language restriction. Study Selection Inclusion criteria: cross sectional or cohort studies that included BMD measured either by DXA, pQCT and/or QUS in youth (age <20 years) with type 1 diabetes and matched controls. Data extraction Total body (TB), lumbar spine (LS) and femoral BMD (DXA); tibia, radius and lumbar spine (pQCT); and phalanx and calcaneum (QUS). Weighted mean difference (WMD) or standardized mean difference (SMD) were estimated and meta-regression was performed using age, diabetes duration and HbA1c as covariates. Data Synthesis We identified 1300 non-duplicate studies; 46 met the inclusion criteria, including 2617 cases and 3851 controls. Mean age was 12.6 ± 2.3 years. Youth with type 1 diabetes had lower BMD: TB (WMD -0.04 g/cm2, 95% CI -0.06 to -0.02, P=0.0006); LS (-0.02 g/cm2, -0.03 to -0.0, P = 0.01); femur (-0.04 g/cm2, -0.05 to -0.03, P<0.00001); tibial trabecular (-11.32 g/cm3,-17.33 to -5.30, P=0.0002), radial trabecular (-0.91, -1.55 to -0.27, P=0.005); phalangeal (-0.32, -0.38 to -0.25, P<0.00001) and calcaneal (SMD -0.69, -1.11 to -0.26, P=0.001). Using meta-regression TB BMD was associated with older age (coefficient -0.0063, -0.0095 to -0.0031, P=0.002), but not longer diabetes duration or HbA1c. Limitations Meta-analysis was limited by the small number of studies using QUS and pQCT and lack of use BMD z-scores in all studies. Conclusions Bone development is abnormal in youth with type 1 diabetes, assessed by multiple modalities. Routine assessment of BMD should be considered in all youth with type 1 diabetes.

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Faculty Opinions recommendation of Bone Mineral Density and Type 1 Diabetes in Children and Adolescents: A Meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.740512255.793588285 ◽

2021 ◽

Author(s):

Madhusmita Misra

Keyword(s):

Bone Mineral Density ◽

Type 1 Diabetes ◽

Children And Adolescents ◽

Bone Mineral ◽

Meta Analysis ◽

Mineral Density

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Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

Non-Coding RNA ◽

10.3390/ncrna4040037 ◽

2018 ◽

Vol 4 (4) ◽

pp. 37 ◽

Cited By ~ 15

Author(s):

Giuseppina E. Grieco ◽

Dorica Cataldo ◽

Elena Ceccarelli ◽

Laura Nigi ◽

Giovanna Catalano ◽

...

Keyword(s):

Bone Mineral Density ◽

Type 1 Diabetes ◽

Bone Loss ◽

Bone Metabolism ◽

Bone Remodeling ◽

Bone Mineral ◽

Bone Fragility ◽

Bone Homeostasis ◽

Mineral Density

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.

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