The causes of bone scintigram hot spots in fluoride-treated osteoporotic patients

We previously described new bone formation in fluoride-treated osteoporotic patients. Since then, several investigators have contended that fluoride-induced "hot spots," as seen on bone scintigrams, represent stress fractures. To further evaluate this issue we analyzed scintigrams, radiographs, and quantitative computer tomography (CT) scans of the spine and femoral condyles from 129 patients, obtained before and during therapy. Hot spots, new or of increased intensity, were more than twice as common in the weight-bearing peripheral skeleton than in nonweight-bearing sites (p less than 0.001). The hot spots were usually diffuse, multiple, bilateral, and mostly seen early in therapy, a pattern quite different from that expected of stress fractures. Previously, we postulated that mechanical stress and fluoride act synergistically to stimulate new bone formation. If this hypothesis were correct, we would expect to see a greater increase in femoral condyle bone density in patients with hot spots. Consistent with this hypothesis, patients who developed hot spots in the knees had a greater increase in condylar density (22 +/- 2.5 vs. 9 +/- 3.3 mg/cc) than those without hot spots and stress fractures were not seen in either group. Additionally, patients with more than 5 hot spots in the peripheral skeleton had greater increases in spinal and condylar density than those with fewer than 5 hot spots. Finally, stress fractures were found in less than 2% of our patients. While we do not exclude the possibility that some additional patients may have had stress fractures, our data support the hypothesis that the great majority of hot spots seen on the scintigrams are the sites of new bone formation.