Faculty Bibliography

OBJECTIVES: (a) To develop a reliable and reproducible system for distraction osteogenesis in the rat to establish a model for future investigations of bone repair and regeneration. (b) To describe and characterize the histological events in distraction osteogenesis in the rat and to determine whether cartilage development is a normal component of the process. STUDY DESIGN: Species-specific, longitudinal time study. METHODS: Twenty rats underwent production of a middiaphyseal femoral osteotomy and application of a monolateral external fixator specifically designed for distraction. Animals were divided into five groups based on the time and extent of lengthening. RESULTS: During distraction, gap tissue showed collagen bundles and fibroblasts that were oriented longitudinally to the direction of the distraction force. Woven bone appeared to be laid down on these collagen scaffolds, and the newly formed vascular sinuses appeared to be the sites from which bone formation was initiated within the distraction gap. All groups undergoing active distraction showed intramembranous ossification in the distraction gap and endochondral ossification peripherally. However, when distraction was discontinued, endochondral ossification was observed in the gap. CONCLUSION: Distraction produces an environment in the distraction gap that suppresses the formation of cartilage. The formation of cartilage by injured periosteum, however, is obligatory and does not appear to be influenced by distraction. Bone formation within the distraction gap occurs where angiogenesis develops

Direct physical injury to bone marrow is associated with a systemic osteogenic response. However, blood loss, a condition that stimulates hemopoietic stem cells, also may activate osteoprogenitor cells in the bone marrow. To determine if bleeding induces a systemic osteogenic response, the mineral appositional rates and osteoblast numbers were determined in the bones of rats that were subjected to controlled cardiac bleeding and compared with those of rats subjected to ablation of their tibial bone marrow. In addition, a study of the kinetics of the osteogenic responses during the first 10 days after operative treatment was performed by quantitating the serum levels of biochemical indices known to be associated with systemic bone formation. The results showed that animals that sustained acute blood loss (1% or 3% body weight) or injury to their tibial bone marrow had statistically significant increases in mineral appositional rate, osteoblast number, and serum levels of osteogenic growth peptide. The kinetics studies showed that osteogenic growth peptide levels peaked on the tenth postoperative day and declined sharply thereafter. An enhancement of serum osteocalcin activity occurred only on the second postoperative day, was increased in all experimental groups when compared with untreated control animals, but immediately declined to baseline levels. Alkaline phosphatase activities increased in the experimental groups, peaking on Day 10 after tibial bone marrow ablation and on Day 12 in the group that underwent bleeding. These findings suggest that bleeding alone, independent of any skeletal trauma, may evoke a systemic osteogenic response. This response is similar in its timing and magnitude to that which has been shown to follow direct physical injury to bone marrow. The observation that systemic bone formation follows bone marrow activation induced by two different stimuli suggests that these responses may be mediated by common regulatory mechanisms. The ability to trigger or control these responses may form the basis for future therapeutic strategies to enhance bone formation.