Clinical and experimental studies of osteogenesis in dogs

Abstract

Growth hormone stimulates bone healing Bone is one of the few tissues capable of complete regeneration. The mechanisms behind this phenomenon are of great interest not only in understanding the process of bone formation, but also in gaining insight into the regeneration of non-skeletal tissues. Distraction osteogenesis, in which bone formation is induced under gradual distraction of two bone surfaces, can be used both as an orthopaedic treatment option and as an experimental model to investigate the role of growth factors in bone regeneration. In this thesis we demonstrate that the expression of growth hormone receptor in distraction-induced bone regenerate is significantly higher than in osteotomy-induced new bone during the consolidation phase of the bone regenerate. We conclude that up-regulation of growth hormone receptor expression may enhance sensitivity to endogenous systemic growth hormone and thus promote consolidation of the bone regenerate after distraction osteogenesis. Based on these findings we hypothesized that local continuous growth hormone administration stimulates bone healing in a canine critical-sized bone defect model. Treatment with growth hormone resulted in healing of bone defects, but without an additional effect of local infusion. Growth hormone administration increased circulating levels of insulin-like growth factor-I and insulin-like growth factor-II. We conclude that continuous infusion with growth hormone stimulates bone healing in this critical-sized bone defect model. In addition to a direct effect of growth hormone, increased plasma concentrations of insulin-like growth factor-I and insulin-like growth factor-II most likely induce bone formation. Commercially available immunoassay kits for osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen were evaluated in monitoring bone formation and bone resorption, respectively, during distraction osteogenesis. Plasma levels of these markers did not reflect the differences in the amount of newly formed bone induced by a distraction procedure or healing of an osteotomy. We conclude that the bone markers osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen are not effective in monitoring bone formation and bone resorption in this canine model of distraction osteogenesis. Delayed-image bone scintigraphy was evaluated in quantitatively assessing distraction-induced bone formation. Distraction osteogenesis and bone healing of an osteotomy resulted in increased delayed-image scintigraphy ratios not only in the affected crus, but also in the adjacent femur. Delayed-image bone scintigraphy was not effective in differentiating between the amounts of newly formed bone. We conclude that delayed-image bone scintigraphy is not adequately sensitive in quantitatively monitoring bone formation, but may be useful as an early predictor of bone healing. Incongruity of the elbow joint and osteoarthritis of the elbow and antebrachiocarpal joint are major complicating factors in treating antebrachial growth deformities in dogs. Treatment with a circular external skeletal fixation system and a lengthening procedure was effective in correcting angular and rotational growth deformities. Nevertheless, it was not possible to completely restore all antebrachial length deficits. Initial elbow osteoarthritis, initial function, and radial and ulnar length deficits were identified as prognostic factors in dogs with antebrachial growth deformities. These factors should be addressed to predict the functional outcome of treatment with a lengthening procedure.