Changes in bone microarchitecture and biomechanical properties in the th3 thalassemia mouse are associated with decreased bone turnover and occur during the period of bone accrual.
Osteoporosis and fractures occur frequently in patients with beta-thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the beta chain of hemoglobin. In this study, we determined the bone abnormalities of the th3 thalassemia mouse, generated by deletion of the mouse beta-chain genes. The heterozygous th3/+ mouse has moderate anemia and serves as a model of beta-thalassemia intermedia, which represents the mild thalassemia phenotype. The th3/th3 mouse has lethal anemia and is a model of beta-thalassemia major, which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls, (1) microCT of trabecular bone showed decreased bone volume fraction, number of trabeculae, and trabecular thickness in both th3/+ and th3/th3 (P < 0.05); (2) cortical bone analysis showed thinner cortices and increased marrow area in th3/+ (P < 0.05); (3) microCT abnormalities in th3/+ mice were present by 2 months and did not worsen with age; (4) histomorphometry was significant for decreased bone formation and resorption in both th3/+ and th3/th3, and expression of cathepsin K and osteocalcin from bone of both th3/+ and th3/th3 animals was reduced (P < 0.05); (5) biomechanics showed reduced maximum load, maximum moment, and structural stiffness in both th3/+ and th3/th3 (P < 0.01). In conclusion, the th3 mouse model of thalassemia manifests bone changes reminiscent of those in humans and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover and develop early during the period of bone accrual.
Vogiatzi
Maria G
MG
Department of Pediatrics, Weill Cornell Medical College, 525 East 68th Street, New York, NY 10065, USA. mvogiatz@med.cornell.edu
Tsay
Jaime
J
Verdelis
Kostas
K
Rivella
Stefano
S
Grady
Robert W
RW
Doty
Stephen
S
Giardina
Patricia J
PJ
Boskey
Adele L
AL
D000818:Animals; D001696:Biomechanical Phenomena; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones; D004920:Erythropoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000209:etiology / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017550:Spectroscopy, Fourier Transform Infrared; D013789:Thalassemia / Q000150:complications* / Q000235:genetics; D014057:Tomography, X-Ray Computed
Br J Haematol. 2009 Sep;146(5):546-56
19604241
Ann N Y Acad Sci. 1998 Jun 30;850:469-70
9668587
Blood. 2007 Jun 1;109(11):5027-35
17299088
Osteoporos Int. 2001;12(7):570-5
11527055
J Pediatr Endocrinol Metab. 1998;11 Suppl 3:975-7
10091176
Ann N Y Acad Sci. 1969 Nov 20;165(1):427-36
5260165
J Bone Miner Res. 2003 Sep;18(9):1682-8
12968678
Br J Haematol. 2001 Jan;112(1):36-41
11167780
Blood. 2003 Apr 15;101(8):2932-9
12480689
Vib Spectrosc. 2005 Jul 29;38(1-2):107-114
16691288
Br J Haematol. 2000 Dec;111(3):902-7
11122154
Bone. 2006 Apr;38(4):571-5
16298178
Osteoporos Int. 2005 Dec;16(12):1809-14
15928800
Bone. 2007 May;40(5):1308-19
17337263
J Bone Miner Res. 2001 Oct;16(10):1821-8
11585346
N Engl J Med. 2005 Sep 15;353(11):1135-46
16162884
Osteoporos Int. 2009 May;20(5):793-800
18769963
J Bone Miner Res. 2009 Sep;24(9):1565-71
19419303
J Bone Miner Res. 2009 Mar;24(3):543-57
18505376
J Clin Endocrinol Metab. 2003 Aug;88(8):3966-72
12915694