Zoledronic acid – Related osteonecrosis of the jaws. Experimental model with dental extractions in rats

Experimental osteonecrosis: development of a model in rodents administered alendronate

“…However, there is no standard BRONJ experimental model, since most models fail to reproduce clinical reality and do not associate several co-factors that undertake a reliable cause-effect relationship between Bps and disease pathogenesis. 6,7,8,9,15,16,17,18,19,20,21,22,23,24 To the best of our knowledge, this is the first study to demonstrate 100% of BRONJ-like lesions by associating tooth extractions with alendronate in cumulative dosages for the management of rheumatic diseases. 12 The first advantage of our experimental model is the high percentage of bone necrosis achieved.…”

“…12 The first advantage of our experimental model is the high percentage of bone necrosis achieved. The rate of bone lesions in previously published experimental models varies from 0 to 100%, 6,7,8,9,15,16,17,18,19,20,21,22,23,24 and only four papers have reported 100% of BRONJ-like lesions. 8,9,17,18 However, models that reported a bone lesion rate of 100% were developed by exposing animals to supra-therapeutic dose regimens 9,17 or to a high-intensity trauma, 8,18 which represents an artificial scenario.…”

“…20,24 Furthermore, most experimental models reproduced oncologic schedules with high dosages of zolendronate. 7,8,15,16,18,21,22,23,25 However, although zolendronate is undeniably important, it is essential to note that ALN is among the most common Bps prescribed worldwide and is specifically indicated for the treatment of benign diseases, such as osteoporosis, osteopenia, and rheumatic diseases. 1 In this context, to compensate for the differences in potency between alendronate and zolendronate, as well as for the lower plasma concentrations when the subcutaneous route rather than the intravenous route is used, 26 we conclude that the total Bps dose administered over a long period of time is important for the magnitude of the reduction in bone turnover.…”

“…The main local agents include periodontal disease, 15,23 bacterial injections in addition to bone defects, 22 and tooth extractions. 9,16,17,18,19,20,21,24,25,26 The last is undoubtedly the most relevant, since most patients develop BRONJ lesions after tooth extractions, as described in clinical studies. 4,5 This finding could be related to an urgent requirement for wound healing after this surgical procedure, especially during initial phases, and, in the field of Bps, this is worsened since these drugs impair the angiogenesis and resorption process after tooth extractions.…”

Adipose-derived stem cells and platelet-rich plasma for preventive treatment of bisphosphonate-related osteonecrosis of the jaw in a murine model

“…Material and methods 2.1. Study design A rat model was chosen to test four different treatments applied after dental extractions in bisphosphonate-treated animals; to do this, we followed our previously published BRONJ-like disease model (Barba-Recreo et al, 2014), which replicates the histologic and radiographic findings of the human disease. Following this BRONJ model, the bisphosphonate chosen was ZA because of its high relative potency.…”