Active Osteosarcoma at the study endpoint.

<p>a) Rat. Distal Metaphysis of Femur. (H&E. 200x). Replacing normal trabecular architecture are poorly differentiated neoplastic cells that are polygonal to spindle shaped with lightly eosinophilic cytoplasm. b) Rat. Distal Metaphysis of Femur. (H&E. 400x). Neoplastic cells are irregularly polygonal with indistinct cell borders and moderate amounts of cytoplasm. Nuclei contain multiple, distinct nucleoli and a mitotic figure is present (asterisk).</p

Assessment of bone resorption over the region of interest.

<p>(a) There was no difference (p = 0.0627) between groups in osteoclast surface. (b) There was no difference (p = 0.1108) between groups in osteoclast number. (c) TRAP surface showed a statistically significant difference (p = 0.0152) between groups, however, pairwise comparisons (Dunn’s test) was not able to detect which groups.</p

Fluorescent micrograph.

<p>Areas of dystrophic mineralization confounded quantification of single-labeled surfaces. As an alternative variable, digital images of the region of interest were used to quantify the total number of positive florescent pixels. There were no significant differences between treatment groups.</p

Region of interest for micro-CT analysis.

<p>Region of interest for micro-CT analysis.</p

Radiograph severity score over time for each treatment group.

<p>There were no significant differences between treatment groups on any given day of imaging. There was a significant difference over all groups from Day 10 to Day 24 (p ≤ 0.001). Score shown as mean +/- SE.</p

Radiograph severity scoring on a scale from 0–5.

<p>A. 0 –No evidence of tumor-associated osteolysis. B. 1 –Mild trabecular lysis apparent (≤ 50% of the diameter of the femur affected. C. 2 –Moderate trabecular lysis apparent (> 50% of the femur’s diameter affected). D. 3 –Severe osteolysis evident with 1 cortex involved. E. 4 –Severe osteolysis evident with both cortices affected. F. 5 –Fracture.</p

Evidence of previous osteosarcoma.

<p><b>(H&E)</b> a) Distal metaphysis exhibiting trabecular destruction, necrosis, and replacement fibrosis throughout regions of previous tumor burden. The growth plate (asterisk), metaphysis (dagger), and epiphysis (double dagger) are shown for reference. (20x) Note the metaphyseal tumor does not cross the growth plate to the epiphysis, where normal trabecular architecture is evident. b) Loosely organized fibrous connective tissue and necrosis in tumor-burdened areas. (100x).</p

Micro-CT.

<p>3-D reconstructions of normal (top) and tumor-burdened (bottom) trabecular and cortical architecture in the distal metaphysis.</p

Effects of radiation and adjunct therapy on treated bone.

<p>Represented are bone volume (a), and polar moment of inertia (b) in the distal metaphysis of tumor-burdened femora. Data represent mean (+/- SE) values.</p

Representative fluorescent micrograph.

<p>Image illustrates single (line with one arrowhead) and double-labeled surfaces (line with two arrowheads) in trabecular bone.</p