We tested the hypothesis that when one bone of the skeleton is injured, others experience an osteogenic response. Although similar or related phenomena have been observed previously, the purposes of the study were to determine if this response was reproducible, to characterize it in terms of its magnitude and duration, and to show how it is related to the type of injury sustained. To obtain this information, a model was used in which an intramedullary nail was implanted in the femur and a standard closed fracture was subsequently produced. The osteogenic response was measured by histomorphometry. Eighty-four nine-week-old male Sprague-Dawley rats were divided into seven groups of twelve animals each. Groups I and II consisted of control animals in which no injury was produced. In Group-III rats, cortical drilling of the intercondylar notch and piriformis fossa of the right femur was performed, without intramedullary nailing. In Groups IV through VII, half of each group received intramedullary nails only, and in the other half intramedullary nailing was done and a closed transverse diaphyseal fracture was produced. With two different fluorochrome labels, rates of mineral apposition were measured in the left and right tibiae of all animals. The labeling periods differed in each group and were designed to determine when the peak response occurred, how long it lasted, and whether aging during the course of the experiment affected the response. The introduction of an intramedullary femoral nail resulted in a significant and reproducible increase in the rate of mineral apposition in both tibiae of all animals studied. The onset of this response was rapid, the magnitude of peak stimulation was as much as 350 per cent of the rate for the control animals, and the gradual return to baseline levels occurred over a period of three weeks. Injury to the cortex without intramedullary nailing did not produce this response, and the addition of a fracture to a femur that had already been subjected to intramedullary nailing did not alter the response. The differences in rates of mineral apposition during this period were not related to aging. Since no observable changes in resorption of bone occurred in any of the tibiae that were studied, the increase in the rate of mineral apposition was interpreted as an osteogenic response. The finding that this response occurs in uninjured bones distant from the injury suggests that it may be produced by a circulating osteogenic factor. Clinical relevance: The implantation of an intramedullary nail into one bone of the skeleton may be associated with the stimulation of osteogenesis in others. This suggests that, in models used in orthopaedic research, what is done to one bone could affect the ability of another bone to serve as a control. Since these findings are consistent with the existence of a circulating osteogenic factor, it is possible that bone injured in this way releases a substance that affects the metabolism of bone during the period of healing.
