Skeletal Fragility in Endogenous Hypercortisolism

2016 ◽  
pp. 66-73 ◽  
Author(s):  
Gherardo Mazziotti ◽  
Adriano Delgado ◽  
Filippo Maffezzoni ◽  
Annamaria Formenti ◽  
Andrea Giustina
Keyword(s):  
Skeletal Fragility

scholarly journals Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1666
Author(s):  
Dean S. Ross ◽  
Tzu-Hsuan Yeh ◽  
Shalinie King ◽  
Julia Mathers ◽  
Mark S. Rybchyn ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Bone Formation ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Age Groups ◽  
Oral Glucose ◽  
Rna Expression ◽  
High Fat ◽  
Mineral Density ◽  
Skeletal Fragility

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene/protein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance/pre-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.

scholarly journals Skeletal Fragility in Children with Chronic Disease

2016 ◽  
Vol 86 (2) ◽  
pp. 71-82 ◽  
Author(s):  
S. Joseph ◽  
S. McCarrison ◽  
S.C. Wong
Keyword(s):  
Chronic Disease ◽  
Skeletal Fragility

scholarly journals Hip Structural Analysis Reveals Impaired Hip Geometry in Girls With Type 1 Diabetes

2020 ◽  
Vol 105 (12) ◽  
pp. e4848-e4856
Author(s):  
Taïsha V Joseph ◽  
Signe Caksa ◽  
Madhusmita Misra ◽  
Deborah M Mitchell
Keyword(s):  
Type 1 Diabetes ◽  
Hip Fracture ◽  
Structural Analysis ◽  
Bone Age ◽  
Sectional Area ◽  
Hip Structural Analysis ◽  
Hip Geometry ◽  
Cross Sectional ◽  
Skeletal Fragility

Abstract Context Among patients with type 1 diabetes (T1D), the risk of hip fracture is up to 6-fold greater than that of the general population. However, the cause of this skeletal fragility remains poorly understood. Objective To assess differences in hip geometry and imaging-based estimates of bone strength between youth with and without T1D using dual-energy x-ray absorptiometry (DXA)-based hip structural analysis. Design Cross-sectional comparison. Participants Girls ages 10 to 16 years, including n = 62 with T1D and n = 61 controls. Results The groups had similar age, bone age, pubertal stage, height, lean mass, and physical activity. Bone mineral density at the femoral neck and total hip did not differ in univariate comparisons but was lower at the femoral neck in T1D after adjusting for bone age, height, and lean mass. Subjects with T1D had significantly lower cross-sectional area, cross-sectional moment of inertia, section modulus, and cortical thickness at the narrow neck, with deficits of 5.7% to 10.3%. Cross-sectional area was also lower at the intertrochanteric region in girls with T1D. Among those T1D subjects with HbA1c greater than the cohort median of 8.5%, deficits in hip geometry and strength estimates were more pronounced. Conclusions DXA-based hip structural analysis revealed that girls with T1D have unfavorable geometry and lower estimates of bone strength at the hip, which may contribute to skeletal fragility and excess hip fracture risk in adulthood. Higher average glycemia may exacerbate effects of T1D on hip geometry.

scholarly journals BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures

2015 ◽  
Vol 32 (11) ◽  
pp. 2961-2972 ◽  
Author(s):  
Carolina Medina-Gómez ◽  
Alessandra Chesi ◽  
Denise H.M. Heppe ◽  
Babette S. Zemel ◽  
Jia-Lian Yin ◽  
...  
Keyword(s):  
Developmental Differences ◽  
Selection Pressures ◽  
Skeletal Fragility ◽  
Evolutionary Selection

scholarly journals Molecular mechanosensors in osteocytes

Bone Research ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Lei Qin ◽  
Wen Liu ◽  
Huiling Cao ◽  
Guozhi Xiao
Keyword(s):  
Focal Adhesions ◽  
Intercellular Junctions ◽  
Endocrine Regulation ◽  
Phosphate Metabolism ◽  
Bone Homeostasis ◽  
Skeletal Fragility ◽  
Master Regulators ◽  
The Past ◽  
Calcium And Phosphate Metabolism

Abstract Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. The mechanotransduction process in osteocytes is a complex but exquisite regulatory process between cells and their environment, between neighboring cells, and between different functional mechanosensors in individual cells. Over the past two decades, great efforts have focused on finding various mechanosensors in osteocytes that transmit extracellular mechanical signals into osteocytes and regulate responsive gene expression. The osteocyte cytoskeleton, dendritic processes, Integrin-based focal adhesions, connexin-based intercellular junctions, primary cilium, ion channels, and extracellular matrix are the major mechanosensors in osteocytes reported so far with evidence from both in vitro and in vitro studies. This review aims to give a systematic introduction to osteocyte mechanobiology, provide details of osteocyte mechanosensors, and discuss the roles of osteocyte mechanosensitive signaling pathways in the regulation of bone homeostasis.

scholarly journals Bone histomorphometry: a concise review for endocrinologists and clinicians

2010 ◽  
Vol 54 (2) ◽  
pp. 87-98 ◽  
Author(s):  
Carolina A. Moreira Kulak ◽  
David W. Dempster
Keyword(s):  
Bone Formation ◽  
Renal Osteodystrophy ◽  
Bone Histomorphometry ◽  
Bone Biopsy ◽  
Quantitative Information ◽  
Important Research ◽  
Treatment Of Osteoporosis ◽  
Skeletal Fragility ◽  
Concise Review ◽  
Metabolic Bone

Bone histomorphometry is a quantitative histological examination of an undecalcified bone biopsy performed to obtain quantitative information on bone remodeling and structure. Labeling agents taken before the procedure deposit at sites of bone formation allowing a dynamic analysis. Biopsy is indicated to make the diagnosis of subclinical osteomalacia, to characterize the different forms of renal osteodystrophy and to elucidate cases of unexplained skeletal fragility. Bone histomorphometric parameters are divided into structural and remodeling subgroups, with the latter being subdivided into static and dynamic categories. Metabolic bone disorders such as osteomalacia, hyperparathyroidism, hypothyroidism, osteoporosis and renal osteodystrophy display different histomorphometric profiles. Antiresorptive and anabolic drugs used for the treatment of osteoporosis also induce characteristic changes in the bone biopsy. Bone histomorphometry is an important research tool in the field of bone metabolism and provides information that is not available by any other investigative approach.

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