C R Severe Mandibular Atrophy Treated With A Subperiosteal .

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CASE REPORTSevere Mandibular Atrophy Treated With a SubperiostealImplant and Simultaneous Graft With rhBMP-2 andMineralized Allograft: A Case ReportCosimo Loperfido, DDS, MSc1*Juan Mesquida, DDS2Jaime L. Lozada, DMD2A 71-year-old patient was successfully rehabilitated by means of a 3D model-derived, hydroxyapatite-coatedtitanium subperiosteal mandibular implant. The implant was specifically designed to allow bone augmentation.The deficient bone was simultaneously grafted with mineralized bone allograft and recombinant bonemorphogenetic protein 2 (rhBMP–2). The 32-month postoperative cone beam computerized tomographyfollow-up showed vertical bone augmentation beneath the implant frame.Key Words: subperiosteal implant, allograft, BMP, vertical augmentationINTRODUCTIONResorption of the alveolar ridge represents a challenge for dental implantplacement. Through the years, differenttechniques have been used to allowdental implant placement in sites withdeficient alveolar bone volume. In previous decades, subperiosteal implants were extensivelyutilized in patients with severe bone resorption.1,2,3The subperiosteal implant was first described in themid-1940s,4 then further refined by Goldberg5 andLinkow;1 throughout the years it has undergonesignificant changes and improvements in terms ofmaterials and shape.One of the major problems attributed to the useof the early subperiosteal implants was the fibrousencapsulation that led to implant movement duringocclusal load and eventually to bone loss andimplant failure.6 Starting with the early 1970s, theresearchers’ attention focused on how to preventbone resorption, improve bone volume, and allow1Private practice, London, United Kingdom.Loma Linda University School of Dentistry, Loma Linda, Calif.* Corresponding author, e-mail: cosimo.loperfido@gmail.comDOI: 10.1563/AAID-JOI-D-12-001322the integration of the implant with the surroundingbone.In 1972, a preliminary human study demonstrated the feasibility of autogenous bone graft performed simultaneously with a subperiosteal implant.7 A few years later, the same authors showedin a Macaca mulatta monkey study that grafting theatrophic mandible with autogenous bone andhydroxyapatite, while simultaneously placing asubperiosteal implant, led to stable bone formationunderneath the implant at the 6-month follow-up.8During the same time period, similar studiesshowed encouraging results.9 The rationale of usinga bone graft underneath a subperiosteal implantwas based on the possibility of obtaining a moreresorption-resistant alveolar ridge,2 allowing osseointegration of the implant,2 and protecting thealveolar nerve which, in these cases, is usuallydehiscent.7 However, in the early 1980s, the utilityof bone grafts performed alongside subperiostealimplants remained questionable, since long-termresults had not shown substantial differencesbetween grafted and nongrafted mandibles afterimplant placement.6In recent years, interest in bone morphogeneticproteins (BMPs) has grown considerably. BoneJournal of Oral Implantology707

Mandibular Atrophy Treated With Subperiosteal Implant and GraftFIGURE 1. (a) pre-operative CBCT right mandible. (b) pre-operative CBCT left mandible. FIGURE 2. Stereolithographic model ofthe patient’s mandible and complete denture. FIGURE 3. Build-up of the mandibular anatomy to the desired alveolardimension. FIGURE 4. Refractory stone model with the subperiosteal implant created in wax.morphogenetic proteins are multifunctional proteins with a wide range of biologic activities,involving a variety of cell types. Bone morphogenetic proteins belong to the super-family oftransforming growth factor–b.10 BMPs bind specificreceptors to a variety of different cell types,including mesenchymal stem cells, osteoblasts,and osteoclasts. Subsequently, these receptorsactivate second-messenger systems within thecellular cytoplasm, which, in turn, leads to intramembranous bone formation when a high concentration of BMPs is present.11 Although morethan 20 BMPs have been discovered, only BMP 2,4, 6, 7 and 9 have proved to be capable ofdriving multipotent cells into an osteoblasticphenotype culture.12,13The aim of this paper is to present a case inwhich a severely atrophic mandible was successfullytreated with a 3D model-derived titanium-hydroxyapatite (HA)-coated subperiosteal implant andsimultaneous grafting with rhBMP–2/mineralizedallograft.708Vol. XL /No. Six /2014CASE REPORTA 71-year-old healthy female patient presented forimplant treatment for her mandibular edentulism atthe Center for Implant Dentistry, Loma LindaUniversity, California, USA.The preoperative cone-beam computerized tomography (CBCT) showed severe bone resorptionthat included not only all of the alveolar bone, butalso part of the basal bone (Figure 1a and b).Because of severe bone resorption and thepatient’s own wish to avoid extensive bonegrafting, the placement of a subperiosteal implantwas planned.The subperiosteal implant was fabricated byutilizing a modification of the technique describedpreviously by Truitt.14 Briefly, a stereolithographicmodel (Figure 2) was fabricated based on the digitalimaging and communication in medicine (DICOM)information acquired by a CBCT acquisition (I-catClassic, Imaging Sciences International, Hatfield,Penn). The stereolithographic model reproducingpatient mandibular anatomy was built up to the

Loperfido et alFIGURES 5 AND 6. FIGURE 5. (a) Immediate postoperative CBCT follow-up right mandible. (b) Immediate postoperative CBCTfollow-up left mandible. FIGURE 6. (a) 32-month CBCT follow-up right mandible. (b) 32-month CBCT follow-up left mandible.desired alveolar dimensions, utilizing a moldableartificial gingival material (GI-Mask, Coltène Whaledent, Switzerland; Figure 3). After the ideal contourwas achieved, an impression was taken of thestereolithographic model and a refractory stonemodel was created. Subsequently, the design of thefuture subperiosteal implant was created in wax(Figure 4) and then cast in titanium alloy and coatedwith HA particles.The surgical treatment was performed underlocal anesthesia. After a crestal incision fromretromolar to retromolar area, the flap was elevatedand the titanium type-IV hydroxyapatite-coatedsubperiosteal implant (Implantlab, San Diego, Calif)was inserted.After implant insertion, the absorbable collagensponge (ACS) carrier was cut in small pieces andsoaked with rhBMP-2 (Infuse bone graft, Medtronic,Minneapolis, Minn). Subsequently, the pieces weremixed together with mineralized bone allograft(Puros allograft, Zimmer Dental, Carlsbad, Calif) andthe resulting mixture was used to graft thesubperiosteal implant. Primary closure was achievedwith GORE-TEX sutures.Healing was uneventful and sutures wereremoved after 15 days. The implant was loaded 3months later. CBCT was taken immediately aftersurgery (Figures 5a and b) and at 32 months afterimplant insertion (Figures 6a and b). The 32-monthCBCT follow-up showed maturation of the bonegraft and vertical bone gain (Figures 6a and b). Atthe 32-month follow-up, the implant in fullyfunctional occlusion was clinically stable (Figures 7and 8).Journal of Oral Implantology709

Mandibular Atrophy Treated With Subperiosteal Implant and GraftFIGURES 7AND8. FIGURE 7. 32-month follow-up patient’s occlusal view. FIGURE 8. 32-month follow-up patient’s smile.DISCUSSIONThis report is the first documented case in which rhBMP2 (Medtronic) and mineralized allograft (Zimmer Dental) were used with the intent to promotebone regeneration underneath a subperiostealimplant and osseointegration of the implant itself.The shape of our implant followed the guidelinesproposed by James.15,16 The implant rested mainlyon areas that tend to resist the resorption of thealveolar ridge: the genial tubercle and the tworetromolars. This even distribution of forces mayresult in good alveolar bone maintenance. Furthermore, the implant design allowed grafting in thoseareas that are usually deficient of bone, like theparasymphyseal and molar/premolar area. Theimplant was HA coated, in order to promotepossible osseointegration. The available literatureon subperiosteal implants placed simultaneouslyalongside bone grafts is limited and controversial.While different authors agreed on the usefulness ofthe bone graft,2,7–9 in the only long-term studyavailable on the subject, the author concluded thatthere were no significant clinical results, in terms offailure rate and complications, when comparingchromium-cobaltum subperiosteal implants placedwith or without autogenous bone graft harvestedfrom the ilium.6 The same article also pointed outthat some bone gain was evident at 1-yearpostoperative panoramic X rays, but still theimplant success rate was around 68% at the 5-yearfollow-up. A more recent retrospective study17showed that HA-coated subperiosteal implantsplaced over a 10-year period had a 91% successrate. However, during those 10 years, 36% ofimplants needed additional corrective interventions.710Vol. XL /No. Six /2014In the same study, the subperiosteal implantsconstructed using a 3D model showed a 100%success rate up to the 9-year follow-up. In our case,we also used a 3D model-derived, HA-coatedtitanium implant. The 32-month CBCT follow-upshowed extensive bone formation. Bone growthphenomenon in severely resorbed mandibles hasbeen previously documented in a large number ofcases in which transmandibular implant systemswere used.18–20 However, those studies were basedon panoramic images and no standardizationtechnique was implemented in order to preventpossible measurement errors.21,22 Bone growth wasalso reported for ramus frame implants.23 A case ofbone growth after using a subperiosteal implantwas reported by Fish.24 In this case, a tripodal HAcoated subperiosteal implant placed in 1985showed bone growth above the mandibular canalin a panoramic X ray taken 14 years later. Bonegrowth was confirmed also at clinical re-entry. Allprevious reports of bone growth in severelyresorbed mandibles speculated that the insertionand the loading of those different implants mayhave induced a physiologic ‘‘positive’’ microstrain tothe bone, which, over time and in accordance withWolff’s law,25 promoted bone apposition. In ourcase, as in the case described by Fish,24 the HAcoating of the implant may have played asignificant role in bone apposition; presumably,bone apposition could have happened over timewithout the additional use of rhBMP–2 andmineralized allograft, but it is very likely that theseactively promoted bone formation.26–30 RhBMP–2(Infuse bone graft) were used ‘‘off-label’’ in theattempt to achieve extensive bone formation

Loperfido et alwithout resorting to the ‘‘osteoinductive’’ autogenous bone. The rationale for combining them with amineralized allograft was to integrate an osteoinductive material (BMPs) with an osteoconductivematerial (allograft) in order to possibly enhancebone regeneration. A human, randomized, controlled clinical and histomorphometric studyshowed that combining BMP–2 with an osteoconductive bone substitute material (xenograft) in thetest group enhanced the maturation process ofbone regeneration and increased the graft-to-bonecontact, compared with controls, where the samematerial was used alone.31 In a rabbit calvariummodel on vertical guided bone regeneration, theuse of rhBMP–2/ACS combined with osteoconductive bone substitute materials resulted in a greateramount of bone formation than the one producedwith the osteoconductive bone substitute materialsalone or rhBMP–2/ACS and blood clot.32 Furthermore, in a case report where a maxillary sinus wasgrafted with the same graft materials used in ourcase (Infuse bone graft and Puros allograft), thebone core biopsy showed new bone formation indirect contact with the allogenic bone, whichappeared to have acted as scaffold.33 A combination of Infuse bone graft and Puros allograft wasused also to attain successful bone regeneration inan alveolar cleft palate patient.34 In our case reportno jig was used to standardize the i-CAT images.However, we tried to be as accurate as possible. Weused as landmark references the area immediatelydistal to the radiographic image of the digastricfossae (for the pre-op and post-op i-CAT images)and the canine abutments of the subperiostealimplant (for the post-op i-CAT follow-up). The crosssectional images were closely approximated to thearea corresponding to the canine position. Theauthors are fully aware of the fact that the imagespresented in this article are not entirely superimposable; therefore, they decided not to include anylinear measurements in this report. However, inspite of the fact that some margins of error mayexist, the preoperative, immediate postoperativeand 32-month postoperative images clearly showvisual evidence of the amount of bone regenerationachieved as well as the preoperative bone levelstatus. Postoperative bone formation appears to bethe result of a regenerative process, rather than justan adaptation of the bone under the stimulus of theimplant load. In all probability, the subperiostealimplant frame acted as a rigid barrier, whichallowed bone regeneration. Therefore, the subperiosteal implant shape may also play an importantrole in these types of cases.In our case report, the postoperative follow-upwas uneventful and the patient did not experienceany adverse events. The most frequently reportedadverse events with autogenous bone or BMPsgrafting procedures are mainly pain, oral edema,face edema, and oral erythema. In certain cases,edema may have an important clinical relevance.Evaluation of studies comparing face edema as anadverse event after grafting procedures withautogenous bone or BMPs for oral and maxillofacialapplications showed a higher incidence, althoughnot statistically significant, of face edema whenBMPs were used.35 It is worth noting that thecollective data from the same studies mentionedabove, showed that the BMPs group had feweradverse events than the autogenous bone graftgroup.35 BMPs induce recruitment of inflammatorycells and fluids and may potentially cause severesoft tissue swelling. This edema, as shown in a ratmodel, is dependent on the dosage.36 To theauthors’ knowledge, in dental literature there areno documented cases of dangerous swelling afteruse of BMPs. However, recent orthopedic andpediatric surgery literature reports adverse softtissue swelling, which is often associated with an‘‘off-label’’ use of BMPs, leading to serious complications.37–42 It is believed that edema is the reasonwhy BMPs are approved only for lumbar spinesurgery and not for cervical spine surgery. As in ourcase, whenever large amounts of BMPs are used‘‘off-label’’ in the mandible, a potential edema of thefloor of the mouth, which may occur few days afterthe surgery, has to be taken into considerationbefore planning such a procedure, in order toprepare for potential complications.CONCLUSIONGrafting the atrophic mandible with mineralizedallograft and rh-BMP-2 at the time of subperiostealimplant insertion may lead to substantial boneformation.Additional studies are needed to evaluate theextent to which rhBMP–2/mineralized allograft maybe useful when used in conjunction with subperiosteal implants, and whether this technique canJournal of Oral Implantology711

Mandibular Atrophy Treated With Subperiosteal Implant and Graftpredictably induce new bone formation and influence the long-term success in those selected casesin which subperiosteal implants may be indicated.Bone morphogenetic proteins (BMPs) show greatpotential in terms of regenerative therapy. However,some concerns still remain, especially regarding thelong-term side effects.43 Human studies usingrhBMP–2 have not demonstrated systemic toxicity.44–48 However, there are no adequate and wellcontrolled studies on pregnant women. There arerising concerns regarding the interference of possiblematernal anti-BMP antibodies49 on BMP-dependentprocesses in a developing embryo50–54 as well theeffects of BMPs on a developing skeleton.55 BothBMPs and BMP receptors have been isolated fromhuman tumors.56,57 BMP-2 has stimulatory andinhibitory effects on different pancreatic tumor celllines.58 Despite the evidence that some BMPs andtheir receptors can be found in tumors, there is noevidence that they are actually carcinogenic. Theirpresence does not mean that they induced neoplasia. They are most likely upregulated.59 Existing datais encouraging, and although long-term follow-up isnot yet available, intermediate data reveals a benignside profile.43BMPs represent a valuable treatment option forregenerative therapy. As previously stated, in thecase presented in this article the patient did notexperience any complications. However, furtherstudies are needed to evaluate the ‘‘off-label’’ useof BMPs.NOTEThe US Food and Drug Administration approvesrhBMP–2 (Infuse bone graft) as ‘‘an alternative toautogenous bone graft for sinus augmentation andfor alveolar ridge augmentation for defects associated with extraction sockets.’’ Furthermore, theclinical trials used for rhBMP–2 (Infuse bone graft)evaluation used only rhBMP–2 by itself, without anyaddition of allograft or xenograft. In our clinicalreport, rhBMP–2 (Infuse bone graft) was used ‘‘offlabel.’’ The patient signed a written consent form foroff-label use prior to the surgical procedure. Theauthors declare no conflict of interest of any sort.Also, this case was not financially or otherwisesupported by any company nor any other venturecapitalist.712Vol. XL /No. Six /2014ABBREVIATIONSACS: absorbable collagen spongeBMP: bone morphogenic proteinCBCT: cone-beam computerized tomographyHA: hydroxyapatiterhBMP–2: recombinant bone morphogenic protein-2REFERENCES1. Linkow Li. Evolutionary design trends in the mandibularsubperiosteal implant. J Oral Implantol. 1984;11:402–438.2. Boyne P, James RA. Advances in subperiosteal implantreconstruction. Dental Clin North Am. 1986;30:259–268.3. James RA, Lozada JL, Truitt PH, Foust BE, Jovanovich SA.Subperiosteal implants. CDA J. 1988;16:10–14.4. Dahl GSA. Regarding the possibility of implanting metalskeletons in the jaws as a base or retention of fixed or removableprostheses [In Swedish]. Odont Tidskrift. 1943;52:440–446.5. Goldberg NI, Gershkoff A. The implant lower denture. DentDig. 1949;55:490–494.6. Bloomquist DS. Long-term results of subperiosteal implants combined with cancellous bone graft. J Oral MaxillofacialSurg. 1982;40:348–352.7. Kratochvil FJ, Boyne P. Combined use of subperiostealimplant and bone-marrow graft in deficient edentulous mandible: apreliminary report. J Prosthet Dent. 1972;27:645–653.8. Kratochvil FJ, Boyne P, Bump RL. 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The implant was specifically designed to allow bone augmentation. The deficient bone was simultaneously grafted with mineralized bone allograft and recombinant bone morphogenetic protein 2 (rhBMP–2). The 32-month postoperative cone beam computerized tomography follow-up showed vertical bone

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