title: Real-time assessment of bone metabolism in small animal models for osteoarthritis using multi pinhole-SPECT/CT.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Orthopaedics, Erasmus University Medical Centre, Rotterdam, The Netherlands. t.piscaer@erasmusmc.nl
authors.forename: T M
authors.initials: TM
authors.lastname: Piscaer
authors.forename: M
authors.initials: M
authors.lastname: Sandker
authors.forename: O P
authors.initials: OP
authors.lastname: van der Jagt
authors.forename: J A N
authors.initials: JA
authors.lastname: Verhaar
authors.forename: M
authors.initials: M
authors.lastname: de Jong
authors.forename: H
authors.initials: H
authors.lastname: Weinans
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents; D016723:Bone Remodeling / Q000502:physiology*; D002358:Cartilage, Articular / Q000000981:diagnostic imaging* / Q000473:pathology; D016022:Case-Control Studies; D004164:Diphosphonates; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging; D006614:Hindlimb / Q000000981:diagnostic imaging; D007461:Iodoacetates; D008297:Male; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium; D013977:Tibia / Q000000981:diagnostic imaging; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007461:Iodoacetates; D013667:Technetium