Approaches to study of ischemia in bone.

Ischemic osteonecrosis is a complication of certain traumatic and a number of idiopathic conditions. The course of the disease may result in collapse of the convex member of a joint and osteoarthritis, often requiring arthroplasty. Increasing incidence in young adults poses a challenge for development of long-term joint prostheses. Current status of research into the disease is discussed and three new models using intravital microscopy described. The first, an arterial occlusion (AO) model, creates ischemia by occluding the common iliac artery exclusively, avoiding direct trauma on other tissues in the limb. The second, a total occlusion (TO) model utilizes classical tourniquet occlusion of the thigh vessels. The third, a venous occlusion (VO) model, is also a tourniquet procedure but it blocks occlusion of the femoral artery with a protective sheath. Preliminary results from AO and TO studies are reported which show that reperfusion injury is detectible after ischemia doses as short as 4 h. This complication was confirmed by observation of leukocyte adherence, secondary ischemia, and abnormal vessel leakage. Also, a new quantitation of osteonecrosis is introduced whereby fluorescently-tagged dead osteocytes and computer-based image processing provide values for an "osteonecrosis index." Viewing of all vascular events is made possible by intravital microscopy through a bone chamber window implanted in rabbit tibias. It is proposed that such chronic visual techniques allow quantitation of events leading to osteonecrosis as well as the revascularization, resorption and bone apposition of creeping substitution which characterizes postischemia recovery.