- 作者：John L. Fowlkes ; Jeffry S. Nyman ; R. Clay Bunn ; Chanhee Jo ; Elizabeth C. Wahl ; Lichu Liu ; Gael E. Cockrell ; Lindsey M. Morris ; Charles K. Lumpkin Jr. ; Kathryn M. Thrailkill
- 关键词：Distraction osteogenesis ; IGF-I ; Diabetes ; Bone formation
- 刊名：Bone
- 出版年：2013
- 出版时间：November, 2013
- 年：2013
- 卷：57
- 期：1
- 页码：36-40
- 全文大小：539 K
Objective
Using a streptozotocin (STZ)-induced mouse model of type 1 diabetes (T1D), we have previously demonstrated that long-term diabetes inhibits regenerative bone formation during tibial distraction osteogenesis (DO) and perturbs skeletal integrity by decreasing cortical thickness, bone mineral density and bone's resistance to fracture. Because long-standing T1D is also associated with a deficiency of insulin-like growth factor I (IGF-I), we examined the effects of systemic IGF-I treatment on skeletal microarchitecture and strength, as well as on bone formation in diabetic mice.Research design and methods
Streptozotocin-induced diabetic or control mice were treated with recombinant human IGF-I (rhIGF-I, 1.5 mg/kg/day as subcutaneous infusion) or vehicle throughout a 14 day DO procedure. Thereafter, trunk blood was assayed for glucose, insulin, rhIGF-I, mouse IGF-I and leptin. Bone formation in distracted tibiae was quantified. Effects on cortical bone strength and trabecular bone architecture were assessed by ¦ÌCT analysis and three-point bend testing of contralateral femurs.
Results
New bone formation during DO was reduced in diabetic mice but significantly improved with rhIGF-I treatment. The contralateral femurs of diabetic mice demonstrated significant reductions in trabecular thickness, yield strength and peak force of cortical bone, which were improved with rhIGF-I treatment. rhIGF-I also reduced intracortical porosity in control mice. However, treatment with rhIGF-I did not normalize serum glucose, or correct concurrent deficiencies of insulin or leptin seen in diabetes.
Conclusions
These findings demonstrate that despite persistent hyperglycemia, rhIGF-I promoted new bone formation and improved biomechanical properties of bone in a model of T1D, suggesting that it may be useful as a fracture preventative in this disease.