# Current Trends in Adjuvant Therapies for Medication-Related Osteonecrosis of the Jaw
## 3 Results and Discussion
### Recombinant Human Bone Morphogenetic Protein-2  
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a protein belonging to the transforming growth factor-\(\beta\) superfamily. It is currently the only Food and Drug Administration-approved osteoinductive growth factor used as a bone graft substitute. Owing to its osteoinductive properties, rhBMP-2 has been used for clinical applications requiring bone tissue regeneration in orthopedic and oral-maxillofacial surgery [37]. It promotes osteoblast differentiation through BMP receptors present in osteoclasts. Thus, rhBMP-2 shows osteoclast activity and promotes favorable bone remodeling [37]. Oversuppression of bone remodeling is considered central in the pathogenesis of MRONJ, arising from pharmacologic inhibition of osteoclast activity [38]. Therefore, the positive effect of rhBMP-2 on bone remodeling in MRONJ patients might involve relieving oversuppression. Appropriate scaffolds are necessary for the long-term application of rhBMP-2 to the defect area to maximize the bone remodeling effect. These include tricalcium phosphate, demineralized bone matrix, hydroxyapatite, and absorbable collagen sponges (ACS). The collagen sponges are versatile, highly biocompatible, easy to use, relatively inexpensive, and the least immunogenic scaffolds. The release period of rhBMP-2 in combination with ACS (rhBMP-2/ACS) is twice faster than without ACS [39]. In addition, rhBMP-2/ACS \begin{table}
\begin{tabular}{c c c c c c c c c c} \hline \hline
**Reference** & **Total Pt** & \begin{tabular}{c} **Medical** \\ **Condition** \\ \end{tabular} & **BP Route** & \begin{tabular}{c} **Duration** \\ **(Years)** \\ \end{tabular} & \
\begin{tabular}{c} **Trigger** \\ **Event** \\ \end{tabular} & **Stage** &
\begin{tabular}{c} **Surgical** \\ **Tx** \\ \end{tabular} & **Outcome** \\ \hline [PERSON] et al. (2012) [27] & 6 & OP & Oral & [PERSON] & NA & 2 or 3 & 100\% & 1-3 & Favorable \\ [PERSON] et al. (2013) [28] & 1 & OP & NA & 2.7 & Spon & NS & None & 8 & Favorable \\ [PERSON] et al. (2013) [59] & 2 & NA & Oral & 4.5 & Spon & 3 & 50\% & 3 & Favorable \\ [PERSON] et al. (2014) [30] & 15 & OP & Oral/IV & 3 & Ext/Info/Spon & 2 or 3 & 80\% & 6 & Favorable \\ [PERSON] et al. (2015) [26] & 10 & NA & Oral & 4.3 & Ext/Info & 2 or 3 & 100\% & 4-24 & Favorable \\ [PERSON] et al. (2016) [31] & 1 & OP & Oral & 2 & Ext & 3 & 100\% & 18 & Favorable \\ [PERSON] et al. (2017) [35] & 1 & OP & Oral & 6 & Imp & 3 & 100[PERSON] & 5 & Favorable \\ [PERSON] et al. (2017) [33] & 6 & OP & Oral & 0.5-15 & NA & 2 or 3 & 100\% & 1-4 & Favorable \\ [PERSON] et al. (2019) [34] & 1 & OP & Oral & 4 & Imp & 3 & None & 2 & Favorable \\ [PERSON] et al. (2020) [23] & 29 & OP & Oral/IV & [PERSON] & Ext/Info & 1-3 & 38\% & 0.3-26 & Favorable \\ [PERSON] et al. (2020) [35] & 12 & OP & Oral & 1-10 & NA & 2 or 3 & None & 6 & Favorable \\ [PERSON] et al. (2020) [36] & 34 & OP/CA/MM & NA & NA & Ext/Imp/Spon & 0-3 & 40\% & 2 & Favorable \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Human studies of teriparatide administration for medication-related osteoinecrosis of the jaw (MRONJ) treatment in the past 10 years. promotes faster bone formation than rhBMP-2 combined with tricalcium phosphate or platelet-rich fibrin-mixed tricalcium phosphate [40]. The bone regenerative effect of rhBMP-2/ACS has been demonstrated in patients with MRONJ. Following surgical treatment, rhBMP-2/ACS increases the rate of new bone formation [41]. Moreover, rhBMP-2/ACS and miniplates are associated with a good prognosis in MRONJ patients [42]. Recent human studies on using rhBMP-2/ACS in MRONJ are summarized in Table 2.  
Since MRONJ patients are mostly elderly and have comorbidities, carefully deciding the treatment plan based on the patient's condition is of paramount importance. Although rhBMP-2 is the only approved bone graft substitute, it provokes side effects such as swelling, seroma, inflammation, and carcinogenicity [43]. Therefore, further studies are needed to evaluate its efficacy and safety for MRONJ treatment.