Small-animal PET/CT assessment of bone microdamage in ovariectomized rats

Microdamage in bone contributes to bone fragility in postmenopausal women. Therefore, it is important to find a noninvasive method to detect microdamage in living bone. PET with (18)F-fluoride has been used for skeletal imaging in clinical studies. However, few studies are undertaken to investigate bone microdamage associated with osteoporosis in vivo using noninvasive means. The aim of our study was to analyze the impact of osteoporosis due to estrogen deficiency on the occurrence of microdamage by observing the change in the uptake of (18)F-fluoride in the tibiae of ovariectomized rats after fatigue loading with small-animal PET/CT. We also explored the feasibility of noninvasive detection of bone microdamage in vivo using a small-animal PET/CT scanner specially designed for rodent study.

Rats were randomized into 2 groups: ovariectomy and sham surgery. These rats were imaged using a dedicated small-animal PET scanner with (18)F-fluoride after the left tibiae were loaded cyclically under the axial compression. The fluoride uptake values were quantified in the tibial mid shafts, and the tibia was obtained for histomorphometric measurements of bone microdamage and osteocyte density. Bone mineral density at the fourth lumbar vertebra and right femur were measured using dual-energy x-ray absorptiometry.

PET image intensity was significantly increased (P < 0.05) in the loaded tibia of the ovariectomy group, compared with that of the sham group. Histomorphometry showed that both crack density and crack length in the loaded tibia were significantly higher (P < 0.05) in ovariectomized rats than in sham rats. The PET image intensity in the loaded tibia was significantly positively correlated with crack length and crack density (which show in histomorphometric measurement) (P < 0.05).

Both small-animal PET/CT and histomorphometric measurement provided evidence that bone microdamage is significantly increased after estrogen depletion. The strong correlation between these 2 measurements suggests that small-animal PET/CT is a useful noninvasive means to detect bone microdamage in vivo.