Physiopathology of Bone Modifications in<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="bold">β</mml:mi></mml:math>-Thalassemia

Perisano, Carlo; Marzetti, Emanuele; Spinelli, Maria Silvia; Callà, Cinzia Anna Maria; Graci, C; Maccauro, Giulio

doi:10.1155/2012/320737

Cited by 42 publications

(27 citation statements)

References 32 publications

(55 reference statements)

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“…We propose that the loss in BMD in malarial and PHZ-induced HA is concurrent to impaired bone formation and to an imbalance favoring bone resorption, as has been proposed for murine and human thalassemia [51], [55]. Since our models represent conditions of acute rather than chronic hemolytic stress, our results also suggest that hemolysis provokes rapid effects in the bone marrow and bones.…”

Section: Discussionsupporting

confidence: 67%

Alterations in Bone and Erythropoiesis in Hemolytic Anemia: Comparative Study in Bled, Phenylhydrazine-Treated and Plasmodium-Infected Mice

et al. 2012

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Sustained erythropoiesis and concurrent bone marrow hyperplasia are proposed to be responsible for low bone mass density (BMD) in chronic hemolytic pathologies. As impaired erythropoiesis is also frequent in these conditions, we hypothesized that free heme may alter marrow and bone physiology in these disorders. Bone status and bone marrow erythropoiesis were studied in mice with hemolytic anemia (HA) induced by phenylhydrazine (PHZ) or Plasmodium infection and in bled mice. All treatments resulted in lower hemoglobin concentrations, enhanced erythropoiesis in the spleen and reticulocytosis. The anemia was severe in mice with acute hemolysis, which also had elevated levels of free heme and ROS. No major changes in cellularity and erythroid cell numbers occurred in the bone marrow of bled mice, which generated higher numbers of erythroid blast forming units (BFU-E) in response to erythropoietin. In contrast, low numbers of bone marrow erythroid precursors and BFU-E and low concentrations of bone remodelling markers were measured in mice with HA, which also had blunted osteoclastogenesis, in opposition to its enhancement in bled mice. The alterations in bone metabolism were accompanied by reduced trabecular bone volume, enhanced trabecular spacing and lower trabecular numbers in mice with HA. Taken together our data suggests that hemolysis exerts distinct effects to bleeding in the marrow and bone and may contribute to osteoporosis through a mechanism independent of the erythropoietic stress.

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Section: Discussionsupporting

confidence: 67%

Alterations in Bone and Erythropoiesis in Hemolytic Anemia: Comparative Study in Bled, Phenylhydrazine-Treated and Plasmodium-Infected Mice

et al. 2012

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“…Furthermore, a low LIC was directly connected with low turnover indices and high TBS, which indicates good bone microstructure. This arrangement underlines the central role of iron status evaluation in thalassemic patients, which is warranted by the close link between iron overload and the development of several complications, and confirms a well-known and well described concept [55][56][57].…”

Section: Discussionsupporting

confidence: 80%

The Role of Trabecular Bone Score and Hip Geometry in Thalassemia Major: A Neural Network Analysis

Baldini¹,

Grossi²,

Cappellini³

et al. 2017

Br J Res

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Osteopathy in thalassemia is a very heterogeneous condition; severity depends on multiple factors, interacting through nonlinear mechanisms. Classic statistics have limitations when applied to the study of such highly complex relationships. Currently, an alternative approach of analysis is represented by the artificial neural networks (ANNs), powerful mathematical tools, increasingly applied to analyze multifactorial databases, as considered more appropriate than classic statistics. We adopted this specialized mathematical method to 76 thalassemia major (TM) patients. In all of them dual energy X-ray absorptiometry (DXA) was performed to measure bone mineral density, and two recent developments were included: trabecular bone score, evaluating bone microarchitecture, and hip structural analysis, evaluating hip geometry. The relationships between bone status and endocrine, hematologic, and clinical parameters were investigated. Using a particular ANN (Auto Contractive Map algorithm), the strength of inter-variable association was defined and a connectivity map generated, visually representing the main connections among the entered variables. Iron status indices (ferritin, liver iron concentration) emerged as the most important variables, dividing the map into two sectors, with parameters indicating satisfactory bone condition in the upper, those indicating poor condition in the lower, near the variable "fractures". The Auto Contractive Map highlighted the key role of bone quantity, bone geometry, and microarchitecture in defining thalassemic bone condition. Among numerous available indices, high femoral bone mineral density and low cross-sectional moment of inertia emerged as the gold standard to classify thalassemic patients for prognostic and therapeutic purposes.

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“…31 We therefore investigated whether RAP-536 treatment can alleviate bone complications occurring in Hbb th1/th1 mice. As determined by dual-energy X-ray absorptiometry and microcomputed tomography, tibiae from vehicle-treated Hbb th1/th1 mice exhibited lower bone mineral density (0.070 6 0.002 vs 0.084 6 0.004 g/cm 2 , P , .01), trabecular bone volume (7.8 6 0.9 vs 18.6 6 4.5%, P , .05), and trabecular number (4.5 6 0.01 vs 4.8 6 0.15 N/mm, P , .05) compared with wild type (Figure 6A-C), likely in part as a consequence of increased erythropoietic activity and bone marrow expansion.…”

Section: Rap-536 Reduces Hemolysis A-globin Aggregates and Ros Inmentioning

confidence: 99%

Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia

Suragani

Cawley

et al. 2014

Blood

126

151

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Physiopathology of Bone Modifications inβ-Thalassemia

Cited by 42 publications

References 32 publications

Alterations in Bone and Erythropoiesis in Hemolytic Anemia: Comparative Study in Bled, Phenylhydrazine-Treated and Plasmodium-Infected Mice

Alterations in Bone and Erythropoiesis in Hemolytic Anemia: Comparative Study in Bled, Phenylhydrazine-Treated and Plasmodium-Infected Mice

The Role of Trabecular Bone Score and Hip Geometry in Thalassemia Major: A Neural Network Analysis

Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia

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