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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 (CT). Contralateral tibiae were analyzed using CT. 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 CT 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. Diabetes 54:2875-2881, 2005 T ype 1 diabetes is associated with several disorders of skeletal health, including decreased bone density, an increased risk for osteoporosis (1-6), and fragility fracture (7-9), as well as poor bone healing and regeneration characteristics (10), conditions which all rely, in part, upon an intramembranous component to bone formation. Increasing evidence suggests that skeletal abnormalities in type 1 diabetes may, in part, result from the detrimental effects of type 1 diabetes on bone formation. For example, decreased expression of transcription factors that regulate osteoblast differentiation have been demonstrated in animal models of type 1 diabetes (11). Numerous reports of bone histology in diabetic animals demonstrate decreased osteoblast number, osteoid volume, and mineral apposition rates (rev. in 12). In diabetic rats, plasma osteocalcin concentrations, a marker of osteoblast activity, acutely decline beginning on the 1st day of glucosuria (13). Similarly, serum concentrations of osteocalcin in children with newly diagnosed type 1 diabetes are significantly lower at the onset of disease (14). Serum markers correlated with bone formation (IGF-I, alkaline phosphatase, and osteocalcin) also are significantly lower in diabetic patients with osteopenia compared with those without osteopenia (2), and studies have demonstrated that lower bone mineral density (BMD) in type 1 diabetes is correlated with decreased markers of bone formation and more exaggerated dysregulation of the IGF system (15).The present study was designed to test the hypothesis that type 1 diabetes specifically impedes intramembranous bone formation by using a model of tibial distraction osteogenesis uniquely modified for use ...

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G. A. Ilizarov's clinical insights and experimental biology have developed into what is known today as distraction osteogenesis. Initially used for the treatment of fractures and nonunions, his methods have proven successful for limb lengthening and bone transportation. A brief history of the development of distraction osteogenesis, definition of terms, methods, and monitoring techniques are described. The primary mechanism, intramembranous ossification, is direct bone formation in uniform gradients of mineralization from a central fibrous interzone. New bone is produced from the local host surfaces and quickly remodels to the equivalent macro and microstructure. Blood supply at the focus of distraction, dependency on a latency period, different rates, and rhythms of distraction are all tested and discussed. Data from experimental tibial lengthening in more than 125 animals (dogs, rabbits, and rats) show that distraction osteogenesis provides unlimited new bone formation that remodels at daily rates ranging from 200 to 400 μm. In over 100 clinical cases, patients ranging in age from 18 months to 49 years have regenerated bone at an average rate of 213 μm in adults and 385 μm in children. Approximately 10% of these cases required supplemental bone grafts. The article proposes that distraction osteogenesis might be successfully applied in craniofacial surgery.