Abstract
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 μCT 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.
| Original language | English |
|---|---|
| Pages (from-to) | 36-40 |
| Number of pages | 5 |
| Journal | Bone |
| Volume | 57 |
| Issue number | 1 |
| DOIs | |
| State | Published - Nov 2013 |
Bibliographical note
Funding Information:This work was supported by grants from the Children's University Medical Group fund of the Arkansas Children's Hospital Research Institute (to K.M.T.), the Martha Ann Pugh Diabetes Research Fund (to K.M.T.), the Arkansas Biosciences Institute (to J.L.F.), the Sturgis Charitable Trust for Diabetes Research (to J.L.F.), and in part by National Institutes of Health Grants R01DK055653 and R01DK084045 (to J.L.F.), R01AA012223 (to C.L.K.) and C06RR16517 (to Arkansas Children's Hospital Research Institute). Additional support (to J.S.N.) was provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development.
Funding Information:
Funding source: This work was supported by grants from the Children's University Medical Group fund of the Arkansas Children's Hospital Research Institute (to K.M.T.), the Martha Ann Pugh Diabetes Research Fund (to K.M.T.), the Arkansas Biosciences Institute (to J.L.F.), the Sturgis Charitable Trust for Diabetes Research (to J.L.F.) and in part by National Institutes of Health Grants R01DK055653 and R01DK084045 (to J.L.F.), R01AA012223 (to C.K.L.) and C06RR16517 (to Arkansas Children's Hospital Research Institute), as well as a grant from the Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development (to J.S.N.).
Keywords
- Bone formation
- Diabetes
- Distraction osteogenesis
- IGF-I
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology
- Histology
