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Year : 2014  |  Volume : 18  |  Issue : 6  |  Page : 781-785  

Recombinant human bone morphogenetic protein type 2 in the reconstruction of atrophic maxilla: Case report with long-term follow-up

1 Oral and Maxillofacial Surgeon, Chairman of Implantology, SOEPAR, Curitiba, PR, Brazil
2 Professor of Positivo University, Curitiba, PR, Brazil
3 Private Pratice, Curitiba, PR, Brazil

Date of Submission05-Aug-2013
Date of Acceptance04-Mar-2014
Date of Web Publication19-Dec-2014

Correspondence Address:
Tatiana Miranda Deliberador
Prof. Pedro Viriato Parigot de Souza St, 5300 - CEP 81280 330 - Campo Comprido - Curitiba, PR
Tatiana Miranda Deliberador
Prof. Pedro Viriato Parigot de Souza St, 5300 - CEP 81280 330 - Campo Comprido - Curitiba, PR
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-124X.147437

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Autologous bone is reported by scientific literature as the gold standard for the replacement of the bone loss in maxillary atrophic area. Notwithstanding, this grafting type shows several disadvantages as: The procedure morbidity, limited size of the graft and longer recovering time. Recombinant human bone morphogenetic protein type 2 (rhBMP-2) has been used as bone substitute for the reconstruction of large bone defects. The aim of this case was to report a clinical case exhibiting the reconstruction of the atrophic maxilla through using rhBMP-2 as grafting material associated with absorbable collagen sponge (ACS). At 8 months of following-up, osseointegrated implants were placed. After 2 years and 5 months of following-up, it could be observed an appropriate aesthetical and functional rehabilitation.

Keywords: Bone regeneration, bone transplantation, dental implants, intercellular signaling peptides and proteins

How to cite this article:
Zetola AL, Verbicaro T, Littieri S, Larson R, Giovanini AF, Deliberador TM, Zetola AL, Verbicaro T, Littieri S, Larson R, Giovanini AF, Deliberador TM. Recombinant human bone morphogenetic protein type 2 in the reconstruction of atrophic maxilla: Case report with long-term follow-up. J Indian Soc Periodontol 2014;18:781-5

How to cite this URL:
Zetola AL, Verbicaro T, Littieri S, Larson R, Giovanini AF, Deliberador TM, Zetola AL, Verbicaro T, Littieri S, Larson R, Giovanini AF, Deliberador TM. Recombinant human bone morphogenetic protein type 2 in the reconstruction of atrophic maxilla: Case report with long-term follow-up. J Indian Soc Periodontol [serial online] 2014 [cited 2021 Apr 17];18:781-5. Available from:

   Introduction Top

The rehabilitation of large bone defects may be achieved by different types of grafting materials, from natural or synthetic origin. Autologous grafting is the option exhibiting the highest success rate. Despite of its several advantages, this grafting type may cause the morbidity of the donor area, increase the recovering time of the patient, and may possible result in progressive resorption. Moreover, the grafting availability is limited, demanding the intervention in another region of the body; in some cases, the hospital environment is necessary. [1]

Allogenous grafting can also be employed; however, there is the risk of disease transmission and longer incorporation time of the graft. Considering these aforementioned factors, the research lines have searched for effective bone substitute materials that provided less morbidity. [2] The use of a composite graft of rhBMP-2/ACS-CCFDAB-PRP regenerates bone in large vertical ridge augmentations as predictably as 100% autogenous graft with less morbidity, equal cost, and more viable new bone formation. This composite graft represents an in situ tissue engineering concept that is able to achieve results equivalent to autogenous grafts in large vertical ridge augmentations without donor bone harvesting. [3] The rhBMP-2 was used as a grafting material for sinus augmentation with clinical success. [4]

Biomolecular research on bone repair and development allowed the discovery of a family of bone- and cartilage-forming regulatory proteins in vivo. These proteins were named by Urist, in 1965, as Bone Morphogenetic Proteins (BMP). [5] They present osteoinductive and osteoconductive capacity and are capable of initiating the bone neoformation when placed in extra-bone sites. [6]

BMP body amount is very small. It is secreted by bone marrow cells, platelets, muscle cells and osteoblasts. Hence, researchers started to produce it laboratorially through the cloning and replication of its genetic code, consequently obtaining a cell bank at the desired amount and concentration. [7] The cloned protein was named Recombinant Human Bone Morphogenetic Protein type 2 (rhBMP-2), and it is capable of inducing bone formation at its pure state and high doses. [6],[8]

BMP action depends on the receptor site. Therefore, it is necessary to evaluate whether the site where the protein will be placed is favorable to the migration of growth factors, has the proper skeleton to accommodate it with good blood supply and lack of secretions; also, BMP demands the association with a carrier. [8]

Absorbable collagen sponge (ACS) is a biocompatible material indicated as a carrier. [9] ACS allows the conduction of enough rhBMP-2 at the applied site and assures a uniform distribution without surpassing the site limits. [10] Notwithstanding, ACS does not have the mechanical resistance needed for maintaining the space up to the primary bone formation; therefore it is necessary the use of an additional material to keep this skeleton. [11]

BMPs can be considered safe and effective in bone defect correction and reconstruction. Toxic, immunogenic, or carcinogenic side effects have not been observed with the use of rhBMP-2, because the material is biocompatible and have little immunogenic effect. [11]

The aim of this case was to report a clinical case of the reconstruction of the atrophic maxilla by using rhBMP-2 associated with ACS as grafting material, with a following-up of almost 3 years.

   Case report Top

Patient MB, 52-years-old female, wearing an upper complete denture, sought dental treatment for oral rehabilitation through osseointegrated implants. The patient reported an aesthetical complaint because of the increase of facial wrinkles and masticatory and phonetic difficulty due to the instability provided by the complete denture.

At clinical examination, the complete absence of the upper teeth and the partial loss of the lower teeth were observed [Figure 1].

At the preoperatively imaging examination, the computed tomography revealed the severe atrophy of the anterior area of the maxilla, at both horizontal and vertical directions. Moreover, there was a bilateral maxillary sinus pneumatization [Figure 2].

The following treatments were proposed: (1) Reconstruction of the maxilla through autologous bone graft harvested from either the tibia or the calvaria; (2) reconstruction of the maxilla through allogenous bone graft coming from bone bank; (3) bilateral zygomatic implants and (4) reconstruction of the maxilla through the rhBMP-2/ACS combined. The dental team and the patient agreed with the fourth option.

The surgery was executed in August of 2008 at Zιtola Dental Institute, Curitiba/PR, Brazil. The patient was submitted to both endovenous sedation executed by the anesthesiologist and local anesthesia. After intra- and extra-oral antisepsis, a straight incision was executed on the maxillary alveolar ridge through size 15 scalpel blade from the left to right first molar. Following, a releasing vertical incision was performed on the area of the labial frenulum. The total-thick flap was raised by using a Molt elevator towards to the vestibule bottom to expose the bone remnant [Figure 3].

With the aid of a round diamond bur a window was bilaterally opened in the maxillary sinus (Caldwell-Luc access). Next, the maxillary sinus membrane was lifted and a synthetic bone substitute was grafted (Bone Ceramic 500-1000 micrometers, Straumann, Basel, Suisse) follow the manufacturer's recommendations.

Two 1.5 mm profile titanium plates of 1.5 (OsteoSin, Sγo Paulo, Brazil) were fixed at both sides of the anterior region of maxilla with 5 mm × 1.5 mm screws (OsteoSin, Sγo Paulo, Brazil) [Figure 4]. Next, rhBMP-2/ACS combined (Infuse Bone Graft, 3.2ml, Medtronic Sofamor Danek USA, Inc) was prepared according to the manufacturer's recommendations and placed below the titanium plates [Figure 5]. The collagen membranes were sutured with simple sutures on the plates aiming to prevent the movement of the grafting [Figure 6]. The flap was coronally positioned and sutured with 5-0 Vycril running simple suture.

Post-operative medication comprises amoxicillin 875 mg + potassium clavulanate 125 mg every 12 h; paracetamol, 750 mg, every 6 h; diclofenac sodium, 50 mg, every 24 h; and 0.12% chlorhexidine digluconate every 12 h. Trans- and post-operative period was uneventful without pain, but with edema. After 30 days, the denture was rebased with soft liner material. The patient was followed-up every 2 weeks [Figure 7] during 6 months.

Tomography showed the ridge augmentation after 8 moths [Figure 8]. Eight months after rhBMP-2 surgery was planned installation of implants. The installation of the implants required the removal of the titanium plates [Figure 9]. Six Straumann implants were installed at both the central incisor area (4.0 mm × 10 mm) and at the posterior area of the maxilla (4.0 mm × 12 mm) [Figure 10]. All implants were locked at above 45N and the provisional denture was installed after 4 days [Figure 11] and [Figure 12]. After 6 months, fixed prosthesis on implants was installed.

Clinical and imaging examinations were performed during the post-operative period, the smile analysis not been taken. After 2 years and 5 months of following-up, an satisfactory functional and aesthetical rehabilitation was achieved [Figure 13].
Figure 1: Maxillary alveolar ridge: Occlusal pre-operative view

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Figure 2: Pre-operative tomography: Axial view

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Figure 3: The total-thick flap raised

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Figure 4: Titanium plates fixed

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Figure 5: Material placed below the skeleton created by the titanium plates

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Figure 6: Collagen membrane sutured on the titanium plates

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Figure 7: Maxillary alveolar ridge: 15-day post-operative following-up, occlusal view

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Figure 8: Tomography showing the ridge augmentation after 8 moths

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Figure 9: Reopening procedure, after 8 months to remove the titanium plates and
installed implants

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Figure 10: Panoramic radiograph showing all the implants installed

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Figure 11: Patient's profile wearing the provisional denture

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Figure 12: Patient's profile wearing the provisional denture

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Figure 13: Panoramic radiograph after 2 years and 5 months

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   Discussion Top

BMP's have a large clinical application by the stimulus of the regeneration of bone defects in craniomaxillofacial areas. The protein may be used in Dentistry in the following situations: Bone defect cavities (either tooth sockets or maxillary sinus grafts), [11] thickness and height augmentation (appositional and interpositional grafts), large continuing defects (large bone loss after trauma or tumor exeresis) and cleft lip and palate rehabilitation. [12]

Among the options for the treatment of the case reported here, the first option (autogenous bone graft) was excluded by the team because of its morbidity and the need of a hospital environment and general anesthesia. The graft through bone bank (second option) was excluded because of the higher risk of disease transmission and longer time between bone integration and the installation of the implants. [2] The zygomatic implants (third option) were not chosen because still lacks of long-term scientific evidence. Thus, the fourth option was chosen because it provided less morbidity, faster patient recovering than the other procedures, and it could be performed at an ambulatorial environment. [8]

This present case report demonstrated the clinical success of the use of rhBMP-2/ACS combined in the treatment of severe maxillary atrophy. This success can be partially explained by the osteogenic capacity of rhBMP-2, which occurs because of the differentiation of the undifferentiated mesenchymal cells (UMC) into bone matrix secreting osteoblasts. Additionally, they are capable of modifying cells already differentiated (myoblasts) into osteoblasts. Thus, it can benefit from the cells of the surrounding muscle tissue to help bone neoformation. [13]

To act efficiently, rhBMP-2 demands the combined of a carrier. One of carrier for rhBMP-2 is absorbable collagen sponge (ACS). A clinical study showed that rhBMP-2/ACS combined at a concentration of 1.5 mm/ml was very effective to reach bone regeneration in the treatment of maxillofacial bone defects. [14] In this case report this combination and concentration was employed and favorable clinical outcomes were reached.

The combination between ACS and rhBMP-2 is biocompatible and malleable. Notwithstanding, it does not promote space maintenance, which demands the use of other materials to act as a skeleton and keep the desired volume titanium mesh and plate. Biomaterials such as calcium triphosphate and hydroxyapatite (CTP/HA) has also been used with this purpose. In this case report, the titanium plate was used as a skeleton because it has been successful reported by the literature; effective fixation without possibility of movements; and small surgical trauma during its insertion. [6]

The use of rhBMP-2/ACS combined has been effective to form viable bone to receive osseointegrated implants and functional load. This fact could be verified in this present case report. Satisfactory amount and quality of bone height and thickness was achieved 8 months after the surgery and the placement of six implants was possible, locked close at 45N. The bone quality was clinically evaluated during the installation of the implants; at that moment a type 3 bone [15] was found. The amount and quality of the bone structure could be seen in the post-operative radiographs and tomographies. Additionally, the long-term following-up of this case report showed the effectiveness of this treatment. Nevertheless, some disadvantages should be attributed to this form of treatment, such as high cost and postoperative edema, these findings corroborate the results recently published. [3]

Recently published article reports the clinical success of application and outcomes of the use of a combined approach to treat a patient with a severe alveolar defect with recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier, along with autogenous bone graft, bovine bone mineral, platelet-rich plasma, and guided bone regeneration. [16] Histologically, studies have demonstrated that bone neoformation obtained after the use of rhBMP-2/ACS combination exhibits normal features with viable cells. [11] However, being a relatively new treatment option, there are few clinical studies with this material [17] and do not have systematic reviews on this topic.

In the case reported here, the use of rhBMP-2 combined with ACS as grafting material was efficient, and enabled the long-term successful functional and aesthetical rehabilitation of the patient.

   References Top

Margonar R, dos Santos PL, Queiroz TP, Marcantonio E. Rehabilitation of atrophic maxilla using the combination of autogenous and allogeneic bone grafts followed by protocol-type prosthesis. J Craniofac Surg 2010;21:1894-6.  Back to cited text no. 1
Chen G, Deng C, Li YP. TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 2012;8:272-88.  Back to cited text no. 2
Marx RE, Armentano L, Olavarria A, Samaniego J. RhBMP-2/ACS grafts versus autogenous cancellous marrow grafts in large vertical defects of the maxilla: An unsponsored randomized open-label clinical trial. Int J Oral Maxillofac Implants 2013;28:e243-51.  Back to cited text no. 3
Torrecillas-Martinez L, Monje A, Pikos MA, Ortega-Oller I, Suarez F, Galindo-Moreno P, et al. Effect of rhBMP-2 upon maxillary sinus augmentation: A comprehensive review. Implant Dent 2013;22:232-7.  Back to cited text no. 4
Urist MR. Bone: Formation by autoinduction. Science 1965;150:893-9.  Back to cited text no. 5
Haidar ZS, Hamdy RC, Tabrizian M. Delivery of recombinant bone morphogenetic protein for bone regeneration and repair. Part B: Delivery Systems for BMPs in orthopaedic and craniofacial tissue engineering. Biotechnol Lett 2009;31:1825-35.  Back to cited text no. 6
Granjeiro JM, Oliveira RC, Bustos-Valenzuela, Sogayar MC, Taga R. Bone morphogenetic proteins: From structure to clinical use. Braz J Med Biol Resp 2005;38:1463-73.  Back to cited text no. 7
Ayoub NA, Garb JE, Tinghitella RM, Collin MA, Hayashi CY. Blueprint for a high-performance biomaterial: Full-length spider dragline silk genes. PLoS ONE. 2007;2:e514.  Back to cited text no. 8
Coomes AM, Mealey BL, Huynh-Ba G, Barboza-Arguello C, Moore WS, Cochran DL. Buccal Bone Formation After Flapless Extraction: A Randomized Controlled Clinical Trial Comparing Recombinant Human Bone Morphogenetic Protein-2/Absorbable Collagen Carrier and Collagen Sponge Alone. J Periodontol. 2013 Jul 4. [Epub ahead of print].  Back to cited text no. 9
Hartman EH, Vehof JW, Spauwen PH, Jansen JA. Ectopic bone formation in rats: The importance of the carrier. Biomaterials 2005;26:1829-35.  Back to cited text no. 10
Boyne PJ, Herford AS, Williams RP. Bone morphogenetic protein-induced repair of the premaxillary clef. J Oral Maxillofacial Surg 2007;65:2136-41.  Back to cited text no. 11
Fallucco MA, Carstens MH. Primary reconstruction of alveolar clefts using recombinant human bone morphogenetic protein-2: Clinical and radiographic outcomes. J Craniofac Surg 2009;20 Suppl 2:1759-64.  Back to cited text no. 12
Yamaguchi A, Komori T, Suda T. Regulation of Osteoblast Differentiation Mediated by Bone Morphogenetic Proteins, Hedgehogs, and Cbfa1. Endocr Rev 2000;21:393-411.  Back to cited text no. 13
Triplett RG, Nevins M, Marx RE, Spagnoli DB, Oates TW, Moy PK, et al. Pivotal randomized, parallel evaluation of recombinant human bone morphogenetic protein-2/absorbable collagen sponge and autogenous bone graft for maxillary sinus floor augmentation. J Oral Maxillofacial Surg 2009;67:1947-60.  Back to cited text no. 14
Lekholm and Zarb. Tissue-Integrated prosthesis: Osseointegration in Clinical Dentistry. Chicago: Quintessence; 1985.  Back to cited text no. 15
Sclar AG, Best SP. The combined use of rhBMP-2/ACS, autogenous bone graft, a bovine bone mineral biomaterial, platelet-rich plasma, and guided bone regeneration at nonsubmerged implant placement for supracrestal bone augmentation. A case report. Int J Oral Maxillofac Implants 2013;28:e272-6.  Back to cited text no. 16
Kao DW, Kubota A, Nevins M, Fiorellini JP. The negative effect of combining rhBMP-2 and Bio-Oss on bone formation for maxillary sinus augmentation. Int J Periodontics Restorative Dent 2012;32:61-7.  Back to cited text no. 17


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]


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