Bone Formation Is Impaired in a Model of Type 1 Diabetes
- Kathryn M. Thrailkill1,
- Lichu Liu2,
- Elizabeth C. Wahl2,
- Robert C. Bunn1,
- Daniel S. Perrien34,
- Gael E. Cockrell1,
- Robert A. Skinner45,
- William R. Hogue45,
- Adam A. Carver4,
- John L. Fowlkes1,
- James Aronson5 and
- Charles K. Lumpkin, Jr.1
- 1Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
- 2Arkansas Children’s Hospital, Little Rock, Arkansas
- 3Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
- 4Center for Orthopedic Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas
- 5Department of Orthopedics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
- Address correspondence and reprint requests to Kathryn M. Thrailkill, MD, Arkansas Children’s Hospital, 800 Marshall St., Springer Building, Slot 512-6, Little Rock, AR 72202. E-mail: thrailkillkathrynm{at}uams.edu
Abstract
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 (μCT). Contralateral tibiae were analyzed using μCT. 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 ≤ 0.001) and radiographically (P ≤ 0.05) in diabetic mice compared with nondiabetic mice but preserved by insulin treatment. Serum osteocalcin concentrations were also reduced in diabetic mice (P ≤ 0.001) and normalized with insulin treatment. Evaluation of the contralateral tibiae by μCT 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.
- BMD, bone mineral density
- DO, distraction osteogenesis
- FIZ, fibrous interzone
- μCT, microcomputed tomography
- PMF, primary matrix front
- ROI, region of interest
Footnotes
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- Accepted July 6, 2005.
- Received March 31, 2005.
- DIABETES
