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

Abstract

^99mTc-Methylene diphosphonate (^99mTc-MDP) is widely used in clinical settings to detect bone abnormalities. However, the mechanism of ^99mTc-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 ^99mTc-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 ^99mTc-MDP at different time points, and quantitated for ^99mTc-MDP uptake with a gamma counter. We demonstrated that ^99mTc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The ^99mTc-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. ^99mTc-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 ^99mTc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for ^99mTc-MDP uptake in osteoblasts during bone healing in vivo and in vitro.

MDP: A traditional method to monitor bone healing and osteoblasts

An imaging procedure to detect bone abnormalities and monitor the progress of bone repair has been further validated by research in the USA. The compound ^99mTc-methylene diphosphonate (^99mTc-MDP) contains a radioactive isotope of the element technetium, allowing its uptake into bone and subsequent imaging using computed tomography. This technique is widely used in clinical settings but the relationship of uptake to bone cell development is not well characterized. Bart Willams and co-workers at the Van Andel Research Institute in Michigan and the University of California, USA, studied the uptake of ^99mTc-MDP in the fractured bones of mice during healing. They found a close correlation between the incorporation of ^99mTc-MDP and the development and mineralization of bone-forming cells. This confirms and helps explain the validity of using ^99mTc-MDP to monitor bone abnormalities and healing in humans.

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