1151_IPC_AAP_553102 6/24/02 8:06 AM Page 433 J Periodontol • April 2002 Clinical Comparison of an Enamel Matrix Derivative Used Alone or in Combination With a Bovine-Derived Xenograft for the Treatment of Periodontal Osseous Defects in Humans Diega Velasquez-Plata,* E. Todd Scheyer,† and James T. Mellonig‡ Background: The combination of bone replacement graft materials has been suggested for the treatment of periodontal osseous defects. The purpose of this study was to evaluate the effectiveness of enamel matrix derivative (EMD) combined with a bovine-derived xenograft (BDX) as compared to EMD alone in the treatment of intraosseous defects in patients with moderate to advanced periodontitis. Methods: Sixteen adult patients with at least 2 intrabony defects were egeneration is defined as the entered in this split-mouth design study. Defects were treated with EMD reproduction or reconstitu- alone or EMD + BDX. Reentries were performed 6 to 8 months after ini- Rtion of a lost or injured part.1 tial surgery. The following soft and hard tissue measurements were One of the objectives of periodon- recorded prior to initial surgery and at reentry: probing depth (PD), gin- tal therapy is to regenerate the gival margin location, clinical attachment level (CAL), depth of defect, periodontal attachment apparatus. and crestal bone level. Statistical analyses were performed to determine There must be histological evi- changes in PD, CAL, fill of osseous defect, and crestal resorption. Per- dence of regeneration of alveolar centages of bone fill (%BF) and defect resolution (%DR) were also cal- bone, periodontal ligament, and culated. cementum over a previously dis- Results: The most significant results were that gingival recession was eased root surface to validate true greater for the group treated with EMD alone (0.8 ± 0.8 mm) com- regeneration.2 This histological evi- pared to EMD + BDX (0.3 ± 0.6 mm) (P = 0.04) and bone fill was dence is supported by clinical greater for EMD + BDX (4.0 ± 0.8 mm) compared to EMD alone (3.1 results that include bone fill of ± 1.0 mm) (P = 0.02). The measures for PD reduction, attachment level osseous defects and gain of clini- gain, crestal resorption, %BF, and %DR did not present a statistically sig- cal attachment levels. Currently, nificant difference (P >0.10). several materials have met these Conclusions: This study evaluated the performance of EMD + BDX and criteria in the human model: intra- EMD alone. The results demonstrated that a significant improvement in oral autogenous bone,3-5 deminer- clinical parameters was observed. When comparing both modalities, a alized freeze-dried bone allograft statistically significant difference was only found for gingival recession (DFDBA),6,7 DFDBA with bone and bone fill, yielding a more favorable outcome towards the combined morphogenetic protein (BMP),8 approach. J Periodontol 2002;73:433-440. barrier membranes,9-12 citric acid 13 KEY WORDS application, bovine-derived xenograft (BDX),14,15 and enamel Comparison studies; grafts, bone; enamel matrix derivative; matrix derivative (EMD).16,17 proteins, enamel matrix; periodontal regeneration; follow-up studies. EMD and BDX have recently been introduced as part of the armamentarium for regenerative * Private practice, West Bloomfield, MI; previously, Department of Periodontics, The University of Texas therapy. In the animal model, BDX Health Science Center at San Antonio. † Private practice, Houston, TX; previously, Department of Periodontics, The University of Texas Health has shown its ability to become Science Center at San Antonio. well vascularized and integrated ‡ Department of Periodontics, The University of Texas Health Science Center at San Antonio. with new host bone,18,19 and it has been found to be effective in clin- 433 1151_IPC_AAP_553102 6/24/02 8:06 AM Page 434 EMD Alone and With BDX for Treating Osseous Defects in Humans Volume 73 • Number 4 ical trials.19-23 A human histologic study demonstrated ments were provided when required. Four to 6 weeks a new attachment apparatus in a previously diseased following the initial phase of treatment, a reevaluation root surface in 3 out of 4 specimens, thus indicating was performed to assess probing depth, attachment that periodontal regeneration is possible following graft- level, mobility, and bleeding on probing. An O’Leary ing with BDX.14 Regarding its safety, Cohen et al.24 plaque score43 <20% was required for all patients before reported that a systemic or local immune response proceeding with the surgical phase of therapy. does not develop following implantation with BDX. The Measurements risk of disease transmission for anorganic bovine bone All baseline clinical parameters were recorded the day has been calculated to be 1 in 10.18,25 A recent study of surgery. Measurements were made with a Univer- reported that there may be a small amount of protein sity of North Carolina periodontal probe and recorded (average of 11 µg/g of particles) associated to the to the nearest millimeter at the mid-facial, mid-lingual, mineral phase in commercially available preparations mesial, and distal line angles from the cemento-enamel of BDX, thus suggesting that this type of grafting mate- junction (CEJ) to the free gingival margin (FGM) to rial may be contraindicated for individuals who have a evaluate recession, FGM to base of pocket (BP) to eval- history of an immune response to bovine proteins.26 uate probing depth (PD) changes and CEJ to BP to However, there is no evidence, to date, to indicate that evaluate attachment level changes. Hard tissue mea- this is a valid statement. surements were obtained during surgery as follows: Enamel matrix derivative is obtained from porcine CEJ to alveolar crest (AC) to evaluate crestal height tooth buds.27-29 It consists primarily of amelogenin and changes, CEJ to base of defect (BD) to measure the other related proteins that have remained virtually amount of defect fill and AC to BD to measure defect unchanged during evolution,27,28 maintaining high homo- depth and evaluate defect resolution. Whenever the geneity with human enamel proteins.29 EMD has been CEJ was not present a restoration margin was used reported to be safe and efficient for treating periodontal instead as a fixed point of reference. Only those defects osseous defects in both animal and human trials.30-39 with an intrabony component (AC-BD) of ≥3.0 mm A recent human histological study has shown that were included. The highest measurement values were the use of EMD will result in a regenerative response.17 recorded. Measurements were made by a calibrated It has been suggested that, due to the limited space- examiner who was blind to the treatment rendered. making potential of EMD, it could be mixed with a par- ticle graft to counteract its thixotropic nature.16 Mixing Surgical Procedures bone-replacement grafting materials to take advantage The first site to be treated was randomly assigned of their synergistic effect is not a novel concept.8,40,41 either EMD alone or EMD + BDX through the flip of a The purpose of this study was to evaluate the effec- coin. The alternative graft material was automatically tiveness of EMD§ combined with BDX࿣ as compared assigned to the remaining defect. Local infiltration of to EMD alone in the treatment of intraosseous defects 2% lidocaine containing 1:100.000 epinephrine¶ was in patients with moderate to advanced periodontitis. utilized followed by intrasulcular incisions. Full thick- A separate study will evaluate the effectiveness of BDX ness flaps were elevated from both the buccal and lin- combined with EMD as compared to BDX alone in the gual aspects preserving as much interproximal tissue treatment of intraosseous defects in humans.42 as possible. Granulomatous tissue was debrided from the osseous defect and the root surfaces were pre- MATERIALS AND METHODS pared utilizing ultrasonic and hand instruments remov- Sixteen adult patients 36 to 65 years of age (9 female, ing accretions and altered cementum. All defects were 7 male; 4 smokers, 12 non-smokers) were entered in classified as to the number of walls present. After this study. Each patient presented evidence of 2 radi- appropriate measurements were taken, the root sur- ographic intrabony defects with associated probing faces adjacent to the defect were bio-modified for 2 depths of ≥5.0 mm following initial non-surgical ther- minutes with 24% ethylenediaminetetraacetic acid apy. Patients were systemically healthy and had no (EDTA) gel (pH 6.7)# to remove the smear layer and contraindications for periodontal therapy. Informed con- to facilitate the precipitation of the EMD to the root sent was obtained after explaining the nature of the surface.44 Following root conditioning, the wound was investigation being conducted. Both the study and the rinsed thoroughly with sterile saline. A sterile solution consent form were approved by an Institutional Review of propylene glycol alginate was utilized to reconsti- Board. tute the lyophilized EMD and it was then applied on the Initial periodontal therapy consisted of full mouth root surfaces in an apico-coronal direction. For the scaling and root planing utilizing both hand and ultra- sonic instruments under local anesthesia. Two visits or § Emdogain, Biora, Chicago, IL. Bio-Oss, Osteohealth Co., Shirley, NY. more were required, each lasting approximately 90 ¶ Astra, Westborough, MA. minutes, with oral hygiene instructions. Occlusal adjust- # PrefGel, Biora AB, Malmö, Sweden. 434 1151_IPC_AAP_553102 6/24/02 8:06 AM Page 435 J Periodontol • April 2002 Velasquez-Plata, Scheyer, Mellonig sites receiving a combination of EMD + BDX (experi- Ta b le 1. mental site), the previously described procedure was Number of Sites Based on Location, immediately followed by the insertion of the BDX which had been reconstituted with the remaining EMD. An Tooth Type, Number of Osseous Walls amalgam carrier was utilized to deliver it into place and Treatment and condensers were used to pack the graft to the existing level of the alveolar crest.