Human bone regenerates through patterns of maturation similar to those of bone growth in response to bone defects of any cause. Stable bone healing is achieved when there is an adequate blood supply and immobilization at the site of the defect. For the first 4 weeks, angiogenic and osteogenic cells originate from the surrounding bone walls and periosteum, while woven bone forms around the defect. These processes are governed by various cytokines and growth factors [11–15].
Ettl et al. suggested that although primary closure after cyst enucleation can be accomplished without bone grafts, further research regarding growth factors, osteoblasts, stem cells, and other components is needed to understand this process more fully [16]. Bone defects up to 3 cm in diameter usually undergo complete ossification after 12 months, while larger bone defects may require a longer period of ossification (24 months or more) [17, 18]. In spite of the obvious need for additional treatment to accelerate healing (e.g., bone grafting), such measures cannot always be taken when possible complications such as infection or migration are of concern. Recently, ACS with absorbed rhBMP-2 has been applied in such situations.
In his primate study, Boyne reported that rhBMP-2 alone was useful even without bone graft material for the reconstruction of facial bone defects after mandibular hemisection, implant, and cleft repair [19]. After reviewing the literature on alveolar ridge augmentation, maxillary sinus augmentation, and/or extraction socket preservation, Freitas et al. reported that ACS with absorbed rhBMP-2 appeared to function as an alternative to autografting in alveolar ridge or maxillary sinus augmentation [20]. Balaji reported the use of rib grafting and rhBMP-2 following removal of an aneurysmal bone cyst [2], and in 2014, Lee et al. also reported the use of rhBMP-2 and β-TCP/HA (tricalcium phosphate/hydroxyapatite) in five patients with cysts [21].
Unfortunately, however, there have been some limitations to the use of rhBMP-2 despite the successful outcomes described above. These include the shorter half-life of BMP-2 and its rapid elimination at the application site, which requires a high dose of BMP-2 and thus expensive medical costs, overgrowth of bone, and unwanted side effects, including swelling due to immune reactions [7, 22, 23]. According to a recent report, excessively high doses of BMP-2 may cause oral squamous cell carcinoma [24]. However, we did not observe complications in any of the patients treated at our hospital.
One can compensate for the abovementioned disadvantages of BMP by selecting an appropriate carrier. Currently available carriers include HA, TCP, DBM, hydrogel, and ACS. Referring to the existing literature, Geiger et al. described “enhancement of osteogenic activity of BMP with a restrictive release of BMP at an effective dose during a period coincident with the accumulation and proliferation of target cells” [25]. Li and Wozney reported that the releasing periods of rhBMP-2 were at least twice as long when treatment included the ACS compared with the control treatment without the sponge, and ACS is an appropriate carrier for BMP application [26]. In contrast, in 2008, Carter et al. mentioned that although ACS is of value for the delivery of BMP and offers good space-maintaining ability, it should be used with caution because its overcompressed use may interfere with normal bone formation [7].
Bone density can be assessed by measuring Hounsfield units and has different values depending on the type of bone. Very dense cortical bone is expressed as 600 HU or more, the dense cortical/spongy bone as 400 through 600 HU, and low-density bone as 200 HU or less [8, 9]. In 2013, Tajima et al. reported that the density of peri-implant, new bonelike tissue ranged from 185 to 713 HU (mean ± SD = 323 ± 156.2) [10].
Huh et al. found that combination therapy with bovine bone (Bio-Oss) and rhBMP-2 leads to more new bone generation than does bovine bone monotherapy and that rhBMP-2 enhanced bone regeneration [27]. In our study, the mean OI was higher in the rhBMP-2 treatment group A than in the group B, and the difference was statistically significant for new bone levels with maximum number of Hounsfield units set at 200. This result suggests that rhBMP-2 contributes significantly to new bone generation in the human body as well.
This study had the following limitations: difficulty in determining the margin when measuring postoperative lesion volume owing to the need for intraoperative osteotomy to approach the lesion; several diagnoses of the lesions; preoperative secondary infections due to the lesions; the degree of defect in the bony housing; and no consideration of the number of absorbable collagen sponges or the quantity of rhBMP-2 actually applied during the operation. Nevertheless, this study is meaningful in that we used a quantitative method to analyze the effect of rhBMP-2 in human subjects. Further studies will be needed to perform histomorphometric analyses of the effects of rhBMP-2 in the human body.
