Bone formation is impaired in a model of type 1 diabetes.
The effects of type 1 diabetes on de novo bone formation during tibial distraction osteogenesis (DO) and on intact trabecular and cortical bone were studied using nonobese diabetic (NOD) mice and comparably aged nondiabetic NOD mice. Diabetic mice received treatment with insulin, vehicle, or no treatment during a 14-day DO procedure. Distracted tibiae were analyzed radiographically, histologically, and by microcomputed tomography (microCT). Contralateral tibiae were analyzed using microCT. Serum levels of insulin, osteocalcin, and cross-linked C-telopeptide of type I collagen were measured. Total new bone in the DO gap was reduced histologically (P < or = 0.001) and radiographically (P < or = 0.05) in diabetic mice compared with nondiabetic mice but preserved by insulin treatment. Serum osteocalcin concentrations were also reduced in diabetic mice (P < or = 0.001) and normalized with insulin treatment. Evaluation of the contralateral tibiae by microCT and mechanical testing demonstrated reductions in trabecular bone volume and thickness, cortical thickness, cortical strength, and an increase in endosteal perimeter in diabetic animals, which were prevented by insulin treatment. These studies demonstrate that bone formation during DO is impaired in a model of type 1 diabetes and preserved by systemic insulin administration.
Thrailkill
Kathryn M
KM
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. thrailkillkathrynm@uams.edu
Liu
Lichu
L
Wahl
Elizabeth C
EC
Bunn
Robert C
RC
Perrien
Daniel S
DS
Cockrell
Gael E
GE
Skinner
Robert A
RA
Hogue
William R
WR
Carver
Adam A
AA
Fowlkes
John L
JL
Aronson
James
J
Lumpkin
Charles K
CK
D000818:Animals; D001842:Bone and Bones / Q000737:chemistry; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D019857:Osteogenesis, Distraction; D010455:Peptides / Q000097:blood; D011972:Receptor, Insulin / Q000032:analysis; D013977:Tibia / Q000737:chemistry; D014057:Tomography, X-Ray Computed
D024042:Collagen Type I; D007328:Insulin; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D003094:Collagen; D011972:Receptor, Insulin