Influence of Inflammation-Mediated Osteopenia on the Regional Acceleratory Phenomenon and the Systemic Acceleratory Phenomenon During Healing of a Bone Defect in the Rat

Abstract.

We have previously shown that restoration of a local bone defect in the rat not only leads to a regional acceleratory phenomenon (RAP), but also to a systemic acceleration of osteogenesis (SAP) at distant sites of the skeleton. In this study, we investigated whether specific inhibition of osteoblasts would affect the local RAP and the systemic acceleratory phenomenon (SAP) healing sites. Systemic inhibition of osteoblasts was induced by inflammation-mediated osteopenia (IMO), a nonspecific type of inflammation initiated by S.C. injections of sterile talc. A drill hole defect 1.2 mm in diameter was performed at the midshaft of the left tibia of female rats. On day 7, during the formation phase of the local healing process, IMO did not influence the number of osteoblasts or the bone volume in the marrow cavity of the local healing site, whereas it did lead to a significant reduction of osteoblast number and bone volume at the systemic site (subepiphyseal spongiosa of the tibia). By contrast, on days 14 and 21, during the resorption phase of bone healing, IMO led to a significant reduction in both osteoblast number and bone volume in the marrow cavity of the local healing site. At the same time, however, it did not influence the cortical area of the bone defect where newly formed bone is needed to ensure mechanical stability. In summary, our model of bone healing reveals that a humoral noxious osteoblast stimulus such as IMO is able to inhibit systemically osteoblasts stimulated by SAP, whereas it is not able to inhibit osteoblasts either from producing woven bone during a RAP or from producing bone that is needed to mechanically stabilize a defect.