Calcitonin Administration in a Rabbit Distraction Osteogenesis Model

Abstract

The effect of salmon calcitonin on the maturation of the regenerate bone was assessed in an experimental model in rabbits. Twenty-six New Zealand White male rabbits, approximately 5 months old and weighing 3 to 3.5 kg, were subjected to a mid-diaphyseal tibial osteotomy. After 5 days, the right tibia was lengthened gradually at a rate of 0.375 mm every 12 hours, for 10 days. Ten international units of salmon calcitonin were administered daily subcutaneously to the study group (14 animals), whereas the animals of the control group (12 animals) were injected with a placebo, for the duration of the experiment. The bone mineral density of the regenerate bone was assessed on Days 20, 35, 45, and 55 of the experiment, in both groups, using dual energy xray absorptiometry. No statistical significant difference was found in the dual energy xray absorptiometry measurements between the study and control groups regarding the change of the bone mineral density of the new bone relative to a preoperative baseline measurement. Characteristic time-related changes were observed in the bone mineral density of the regenerate bone during its maturation, which proved to be identical in both groups. It seems that the administration of calcitonin does not enhance regenerate bone mineralization rate and tendency during bone lengthening.

Effects of calcitonin and alendronate on distraction osteogenesis

“…The degree of bone mineralization was monitored at various intervals during experiments with DEXA (dual energy X-ray absorptiometry). Increases in bone density occurred over time, while no significant difference was found between the calcitonin and the control groups [13]. However, in their study a lack of histological and biomechanical evaluation constitutes the weak point of this investigation.…”

“…After a seven day waiting period, distraction was applied to each tibia on a schedule of 2×0.5 mm/day. Furthermore, for group I (control group) a placebo was administered over the distraction period, while for ten days group II received 10 MRC-U (Medical Research Community-Unit) of salmon calcitonin [13] and group III was treated with alendronate (0.5 mg/kg/day in distilled water) [8]. At the end of ten days, distraction was terminated.…”

Stimulation of EP4 receptor enhanced bone consolidation during distraction osteogenesis

“…However, while attempts have been made to determine the therapeutic effect of exogenous application, the results were not satisfactory. Researchers failed to demonstrate the bone-formation-enhancing effect of VEGF 20 and calcitonin 5 on distraction osteogenesis, although IGF, 21 FGF, 7 and BMP 6 have been demonstrated to promote new bone formation. In most of the studies, these cytokines were delivered to the osteotomy gap directly and by single-dose administration because of the strong effect of these factors on other tissues.…”

“…To enhance new bone formation and maturation, and thereby shorten treatment time, the use of adjunctive modalities has been extensively investigated. These include the transplantation of progenitor cells, 3 demineralized bone matrix, 4 the administration of growth factors, [5][6][7] hormones, 8 other peptides, 9 the application of lowintensity pulsed ultrasound, 10 and electromagnetic stimulation. 11 Prostaglandin E2 (PGE2) promotes both bone formation and bone resorption, but ultimately accelerates the former.…”

Novel application of HA‐TCP biomaterials in distraction osteogenesis shortened the lengthening time and promoted bone consolidation

“…However, for the management of larger bone defects caused by trauma, bone infection, and bone tumors, the long duration associated with DO treatment and the bone consolidation phase can cause considerable morbidity for the patients, such as refracture, nonunion, infection of pin hole, etc; 7,9-11 and in clinical practice, there is a need for shortening the treatment time of DO and augmentation of bone consolidation during DO. Various methods for promoting bone consolidation during DO treatment have been studied, such as using physical stimulations, ultrasound, surgical techniques, grow factors, and stem cells, [11][12][13][14][15][16][17][18][19][20][21][22][23][24] but these treatments are not always successful, and require higher cost and additional procedures/facilities/ equipment, that may not readily available. 25 In orthopedics and traumatology a variety of biomaterials has been developed and widely applied in spinal fusion, bone-defect management, and skeletal tissue engineering, with many satisfactory clinical outcomes.…”