The overall objective of this project is to determine the physiologic control mechanism for transport of ions, molecules and antibiotics in normal bone, fractured bone and bone diseases characterized by normal bone remodelling that are important in orthopaedics. The methodology will include measurement of blood flow, transcapillary exchange of tracer ions, and volume distribution of these ions in bone. From measurement of the rate of escape (emergence function) of these ions, we can calculate the permeability to cell wall as well as previous measures of capillary permeability. With an estimate of neutro (t), emergence function, and volume distribution of the tracer ions, it should be possible to measure movement of these ions from tissue to blood. After establishing these methods in control dogs, studies can be directed to fractured bone and animal models with altered hormonal states, i.e., parathyroidectomized dogs or dogs made hyperparathyroid. In addition to ion fluxes, it is planned to measure transcapillary movement of (14C) penicillian in bone and the volume distribution of labelled antibiotics in bone. Studies are planned on formation of the capillary bed in fractures. Fixation techniques for fractures, for example intramedullary rods, plates, and fixation supplemented by methyl methacrylate, will be evaluated by measurement of blood flow, bone remodelling and capillary bed response.