In vivo skeletal imaging of 18F-fluoride with positron emission tomography reveals damage- and time-dependent responses to fatigue loading in the rat ulna.
The skeletal response to damaging fatigue loading is not fully understood. We used (18)F-fluoride PET to describe the time course of the skeletal response following the creation of increasing levels of in vivo, fatigue-induced damage. The right forelimbs of 40 adult rats were loaded in vivo in cyclic compression to four levels of subfracture, fatigue displacement: 30, 45, 65, or 85% of fracture displacement. Rats were injected with a bone-seeking radionuclide ((18)F-fluoride) on days 0 (4 h), 2, 4, 7, 9, 11, 18, 24, and 30, and imaged using a small animal positron emission tomography (PET) scanner. We quantified fluoride uptake in the central 50% of the right (loaded) and left (control) forelimbs. There were significant increases in fluoride uptake in loaded forelimbs compared to control on day 0 for all displacement groups. Normalized uptake (loaded/control) reached peak levels 4 to 9 days after loading. Normalized uptake depended significantly on the level of fatigue displacement. Normalized uptake increased progressively from the 30 to the 45% displacement level (P < 0.001), and from the 45 to the 65% level (P < 0.001) but did not differ between 65 and 85% (P = 0.41). Histologically, we observed a rapid periosteal response with increased vascularity as early as day 1 and abundant woven bone formation between days 3 and 7. Periosteal and woven bone thicknesses were greater in bones subjected to more fatigue displacement. We conclude that a single bout of fatigue loading leads to a transient increase in the uptake of (18)F-fluoride, that the uptake is in proportion to the level of initial damage and is associated with increased vascularity and woven bone formation in the first week after loading.
Department of Orthopaedic Surgery, Washington University School of Medicine, 1 Barnes-Jewish Hospital Plaza, Suite 11300 WP, St. Louis, MO 63110, USA. silvam@wustl.edu
Matthew J
MJ
Silva
Brian A
BA
Uthgenannt
Jerrel R
JR
Rutlin
Gregory R
GR
Wohl
Jason S
JS
Lewis
Michael J
MJ
Welch
D000818:Animals; D015331:Cohort Studies; D015775:Fractures, Stress / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014457:Ulna / Q000000981:diagnostic imaging / Q000293:injuries*; D014458:Ulna Fractures / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D016474:Weight-Bearing