Bone injury response. An animal model for testing theories of regulation

Therapeutic treatment of bone disease and attempts to accelerate normal healing require knowledge of the soluble factors that control bone repair and the specific effects that they produce. To facilitate study of this regulatory system, an animal model involving creation of a hole in the cortex of the rat tibia was developed. Proliferation, differentiation, and callus formation at the injury site were measured more precisely than in previous animal models by means of autoradiographic, histologic, histochemical, and morphometric methods. Several novel features of bone healing were observed, including the following: (1) synthesis of bone matrix in the defect occurred only after a cambial compartment was established by regeneration of the fibrous periosteum and (2) at least 3 kinds of osteoblasts could be distinguished depending on when and where they deposited calcifiable matrix. The model is well suited to evaluating the use of interventional strategies that involve chemical or electrical agents because the cellular parameters of interest can be measured precisely.