Differences between auto-fluorescence and tetracycline-fluorescence in medication-related osteonecrosis of the jaw-a preclinical proof of concept study in the mini-pig

Clin Oral Investig. 2020 Dec;24(12):4625-4637. doi: 10.1007/s00784-020-03332-2. Epub 2020 May 22.


Objectives: Fluorescence-guided bone surgery is a well-established technique in the treatment of medication-related osteonecrosis of the jaw. No histopathological evidence for bone auto-fluorescence is currently available, and thus, any differences from tetracycline-fluorescence remain unclear. Therefore, the goals of this study were to find out if macroscopic and histological differences occur between the auto- and tetracycline-fluorescence in the delineation of viable and necrotic jawbone in the mini-pig.

Materials and methods: According to the proof of concept, osteonecrosis was provoked in eight Göttingen minipigs. Pigs were divided into two groups (AF group: no fluorochrome label; TF group: tetracycline label). Delineation of necrosis and viable bone was evaluated in vivo and in vitro macro-/microscopically, correlated to fluorescence properties and compared between the two study groups.

Results: No macroscopic and microscopic clinical differences were seen in fluorescence between the AF and TF groups. Macroscopic and microscopic viable bone fluoresced green, whereas necrotic bone showed no or only pale fluorescence in both groups. The auto-fluorescence was attributable to the arrangements and structure of collagen and the cell-filled bone lacunae.

Conclusion: Neither in vivo nor in vitro macroscopically differences are apparent between the auto-fluorescence and the tetracycline-fluorescence of bone. The auto-fluorescence is attributable to the arrangements and structure of collagen and the cell-filled bone lacunae. Tetracycline-fluorescence is a mixture of tetracycline (at the bone edges with increased bone formation) and large components of auto-fluorescence.

Clinical relevance: Because auto-fluorescence is easy to apply, reproducible, and does not rely on the subjective impression of the surgeon, it promises to be an important standardized alternative to tetracycline-labeled MRONJ therapy.

Keywords: AR-ONJ; Animal model; BRONJ; Fluorescence-guided bone surgery; MRONJ; Therapy.

MeSH terms

  • Animals
  • Bisphosphonate-Associated Osteonecrosis of the Jaw*
  • Bone Density Conservation Agents*
  • Diphosphonates
  • Fluorescence
  • Proof of Concept Study
  • Swine
  • Swine, Miniature


  • Bone Density Conservation Agents
  • Diphosphonates