Localization of Bone-Seeking Agents in Developing, Experimentally Induced Osteoarthritis in the Knee Joint of the Rabbit

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Abstract
In order to elucidate the uptake and localization of bone-seeking agents in early and advanced osteoarthritis, bone scintigraphy and contact autoradiography were employed in experimental rabbit osteoarthritis, induced by joint instability of the knee. 42 adult rabbits were examined after administration of Tc-methylene diphosphonate given intravenously 1, 2, 4, 6, 12, 26 weeks and 11-2 years postoperatively, 6 animals at each interval. The scintimetric ratio between uptake in the unstable joint vs. control joint had increased as early as one week postoperatively and was highest within the first 3 months. The autoradiograms revealed two localizations of increased mTc-MDP uptake during different stages in osteoarthritic development: early uptake in growing osteophytes and late uptake in subchondral bone. The uptake in the osteophytes was localized to the provisional calcifications of enchondral ossification and could be observed as early as one week postoperatively, before there was any radiographic sign of osteophytes. The osteophyte uptake was responsible for the highest scintimetric ratios registered, but in the advanced state most osteophytes had lost their earlier increased uptake. The late subchondral uptake was seen mostly in the medial compartment of the joint under denuded or eburnated articular surfaces. The results provide a better understanding of the topography of bone scintigraphic uptake in osteoarthritis and indicate that early osteophyte growth is the cause of increased bone scintigraphic uptake in joints free from radiographic signs of osteoarthritis.