Real-time assessment of bone metabolism in small animal models forosteoarthritis using multi pinhole-SPECT/CT

Objective: Destructive techniques such as histology and biochemical assays are still regarded the gold standard to study the effects of novel therapies or etiologic aspects of osteoarthritis in small animal models. These techniques are time-consuming and require many animals. Multi-pinhole single photon emission computed tomography (MPH-SPECT) is a relatively novel, high resolution imaging technique which enables assessment of biological processes in real-time and thus it might provide a good substitute for destructive assessment techniques. Design: For this study, we assessed mono-iodoacetate (MIA) induced osteoarthritic knees in 18 rats. The animals were scanned using MPH-SPECT/CT and a diphosphonate labelled with 99m-technetium as the radioactive tracer to monitor subchondral bone turnover (bone-scan) at 2 (n=18), 14 (n=12) and 42 (n=6) days after injection of MIA. At each time-point six animals were sacrificed and also assessed with high-resolution micro-computed tomography (μCT) and histology. Results: At 2 days after injection of MIA, the MPH-SPECT/CT already showed elevated bone turnover in the affected knee, whereas with histology and μCT we could not detect clear alterations at all this time-point. The increase in bone turnover induced by MIA was elevated further at 14 and 42 days after injection. At this time alterations on histology and μCT scanning also became visible. Conclusions: MPH-SPECT/CT proved to be a highly sensitive assessment technique for experimental osteoarthritis in small animal models, detecting real-time changes in bone turnover at a very early time point, which might make it a valuable technique to measure the direct effect of interventional strategies on osteoarthritis.

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