In Vivo UTE-MRI Reveals Positive Effects of Raloxifene on Skeletal-Bound Water in Skeletally Mature Beagle Dogs

Raloxifene positively affects mechanical properties of the bone matrix in part through modification of skeletal-bound water. The goal of this study was to determine if raloxifene-induced alterations in skeletal hydration could be measured in vivo using ultra-short echotime magnetic resonance imaging (UTE-MRI). Twelve skeletally mature female beagle dogs (n = 6/group) were treated for 6 months with oral doses of saline vehicle (VEH, 1 mL/kg/d) or raloxifene (RAL, 0.5 mg/kg/d). After 6 months of treatment, all animals underwent in vivo UTE-MRI of the proximal tibial cortical bone. UTE-MRI signal intensity versus echotime curves were analyzed by fitting a double exponential to determine the short and long relaxation times of water with the bone (dependent estimations of bound and free water, respectively). Raloxifene-treated animals had significantly higher bound water (+14%; p = 0.05) and lower free water (-20%) compared with vehicle-treated animals. These data provide the first evidence that drug-induced changes in skeletal hydration can be noninvasively assessed using UTE-MRI.