# Fat Graft in Surgical Treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ)
###### Abstract  
Background: Although the published literature has grown exponentially during the last few decades, managing medication-related osteonecrosis of the jaws (MRONJ) remains challenging. Since the first description of adipose-derived stem cells, cell therapy showed promising perspectives in surgical treatment of MRONJ. In this study, the beneficial effect of fat graft in surgical treatment of stage 2 and 3 MRONJ patients was assessed. Methods: A retrospective analysis of the evolution pattern of the disease was conducted comparing the outcomes of MRONJ patients who underwent sequestrectomy followed by fat graft (\(n=9\)) and those who received sequestrectomy alone (\(n=12\)). Results: Improvement of the disease stage was observed in 77.8% vs. 22.2% cases in group A and B, respectively (\(p=0.030\)); disease stability was documented in 11.1% vs. 25.0% cases in group A and B, respectively (\(p=0.603\)); worsening of MRONJ stage was observed in 11.1% vs. 50.0% cases in group A and B, respectively (\(p=0.159\)). Conclusions: Despite the small sample size, this study suggests that fat graft may represent a promising low-risk and cost-efficient adjunctive therapy in the surgical treatment of MRONJ patients. medication-related osteonecrosis of the jaws; MRONJ; BRONJ; fat graft; adipose tissue graft; adipose-derived stem cells; adipose-derived stromal cells; ASC; ASCs; mesenchymal stem cells +
Footnote †: journal: Medical and Surgical Sciences  
+++ ==WARNING: Truncated because of repetitions==  
++  
necrotic bone, should be considered a stage 0 MRONJ. Exposed and necrotic bone or fistulas that probe to the bone in asymptomatic patients (without infections) should be considered stage 1, while the presence of symptoms--such as pain, infections, erythema, purulent drainage--constitutes stage 2 MRONJ. In case these symptoms and signs coexist with the extension of the osteonecrosis beyond the alveolar process, or with a pathological fracture, or with an extraoral fistula, or with the development of oral antral/nasal communication, stage 3 can be diagnosed [1]. Historically, treatment protocols were based on practitioners' knowledge and expertise. In 2019, the Multinational Association of Supportive Care in Cancer (MASCC), the International Society of oral Oncology (ISOO), and the American Society of Clinical Oncology (ASCO) outlined a joined practice guideline based on the AAOMS staging system [4]. According with their comprehensive recommendations, and with the retrieved literature, full mucosal healing above the exposed bone may be considered as an indicator to reflect the resolution of the disease, along with the absence of referred pain and signs of infection. However, this may represent a challenging goal to achieve, as a significant percentage of treated patients typically do not benefit from the received treatments. Moreover, some ongoing controversies exist regarding how the surgeon should decide between a conservative or aggressive treatment [5]. During the last few years, the research in cell therapy revealed interesting perspectives. Mesenchymal stem cells (MSCs) have been proposed as a candidate for MRONJ management due to their capability to differentiate into other mesenchymal tissue, such as bone, cartilage, and adipocytes [6; 7]. Adipose tissue represents an abundant source of autologous MSCs, called adipose-derived stem cells (ASCs), which are easy to be harvested and processed [8]. This cell population has been widely investigated since they were firstly characterized by [PERSON] et al. in 2001 [9], who demonstrated their in vitro differentiation potential. Following the first in vivo investigation by [PERSON] et al. [10], ASCs potential in wound treatment was widely documented [11]. These cells are capable of differentiating into several cell types reproducing ectodermal [12], endodermal [13], and mesodermal [14] tissues to exert numerous paracrine effects on the recipient tissues [15; 16] and to modulate the immune system [17].