99mTC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice

• Published in: Bone research Vol. 3; no. 2; pp. 15013 - 99
• Main Authors: Zhong, Zhendong A, Peck, Anderson, Li, Shihong, Vanoss, Jeff, Snider, John, Droscha, Casey J, Chang, Tingtung A, Williams, Bart O
• Format: Journal Article
• Language: English
• Published: London Springer Nature B.V 09.06.2015; Center for Skeletal Disease Research, Van Andel Research Institute, Grand Rapids, MI, USA%Smal Animal Imaging Facility, Van Andel Research Institute, Grand Rapids, MI, USA; Nature Publishing Group
• ISSN: 2095-4700; 2095-6231
• DOI: 10.1038/boneres.2015.13

99m Tc-Methylene diphosphonate (99m Tc-MDP) is widely used in clinical settings to detect bone abnormalities. However, the mechanism of 99m Tc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography (gamma scintigraphy or SPECT), ex vivo micro-computed tomography, and histology to monitor 99m Tc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with 99m Tc-MDP at different time points, and quantitated for 99m Tc-MDP uptake with a gamma counter. We demonstrated that 99m Tc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The 99m Tc-MDP uptake within the injury sites peaked on day 7 post-injury, while the injury sites were occupied by mature osteoblasts also starting from day 7. 99m Tc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that 99m Tc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for 99m Tc-MDP uptake in osteoblasts during bone healing in vivo and in vitro.