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

Abstract

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.

A critical assessment of the medication-related osteonecrosis of the jaw classification in stage I patients: a retrospective analysis

“…For instance, bleeding in the operating area makes the fluorescence properties difficult to obtain, which might distort the measurements. It is also difficult to use this technique in a sterile operating theater because no currently available devices allow thermic sterilization 22 . However, this technique can assess the extent of necrotic bone with great clinical accuracy 21 , 22 .…”

“…The following procedure was performed during the operation: after surgical bone exposure, the VELscope system Vx (LED Dental, White Rock, BC, Canada) was used to induce and visualize auto-fluorescence of the jawbone. As described previously by our group 21,22 , this method allows the expansion of necrotic bone to be represented with great clinical accuracy. Under the light of the VELscope, viable bone shows a greenish auto-fluorescence, whereas necrotic bone areas show no or only very pale autofluorescence.…”

“…2) Surgical intervention (T1) All surgical procedures were performed under general anesthesia by one surgeon (O.R.) following a previously published surgical protocol 22,23 and adhering to a standardized, intra-institutional protocol from the German guidelines for MRONJ 5 : (1) adjunctive antibiotic therapy; (2) complete removal of necrotic bone; (3) smoothing of sharp bone edges (modeling osteotomy); and (4) secure and well vascularized plastic wound closure.…”

“…Furthermore, inconsistent results have been found, including both over-and underestimation of the extent of MRONJ when comparing the AAOMS stages with various imaging modalities 19 . At present, it seems that determining the true extent of necrosis is only possible intraoperatively using the judgment of experienced surgeons or fluorescence-based methods [20][21][22] .…”

Choosing the Right Partner for Medication Related Osteonecrosis of the Jaw: What Central European Dentists Know

“…Moreover, the effect of bisphosphonates on the osteogenic activity of osteoprogenitor cells cultured on titanium surfaces has been investigated [ 13 ]. Further, innovative therapeutic approaches have been evaluated including fluorescence-guided bone surgery [ 14 ], ozone [ 15 ], advanced-platelet rich fibrin (A-PRF) and injectable-platelet rich fibrin (i-PRF) [ 16 ], and laser combined with platelet-rich plasma [ 17 ]. Discoveries on oral mesenchymal stem cell-derived exosomes have been reported in a recent review [ 18 ].…”