BMP-induced heterotopic bone formation in fetuin-deficient mice

Oral Abstract Session 2: Maxillofacial Pathology/Anesthesia/Maxillofacial Reconstruction/Orthognathic Surgery

Platelet-Rich Plasma: A Preliminary Report in Routine Impacted Mandibular Third Molar Surgery and the Prevention of Alveolar Osteitis Jerome D. Mancuso, DDS, 2520 17th Street W., Suite 302, Billings, MT 59102 (Bennion JW; Hull MJ; Winterholler BW) Purpose: One hundred seventeen patients undergoing elective impacted mandibular third molar removal were enrolled in the study. Median age was 17.2 with a range from 14 to 22. There were 68 males and 49 females, and all females were questioned regarding use of oral contraceptives, the use of which precluded enrollment in the study. Also, the use of tobacco in any form resulted in removal from the study. Inclusive study dates were July 2002 to December 2002. Patients and Methods: The 117 patients underwent elective removal of impacted mandibular third molars in the absence of any clinical pericoronitis, infection, or opposing traumatic occlusion. Platelet-rich plasma (PRP) was prepared as described by the manufacturer by collecting 20 cc of autogenous blood at the time of venipuncture, before intravenous fluids or sedative medications were administered. The specimen was centrifuged using the Harvest Technology Prep 2 centrifuge according to manufacturers’ specifications. The platelet concentrate, containing an average of 338% platelets, was then reconstituted with blood plasma and combined with calcium chloride and topical thrombin to form the platelet gel. The PRP was then placed into either position 17 or 32 by the surgeons (J.D.M. and J.W.B.). The remaining platelet-poor plasma (PPP) was applied over the suture line on the same side to aid in hemostasis. Follow-up evaluation was performed immediately before discharge from the office, at seven days, fourteen days, and thirty days by two other surgeons (M.J.H. and B.W.W.), and compared to the contralateral side. The evaluating surgeons were unaware which side was treated with the PRP. Results: The overall rate of alveolar osteitis in the PRP treated site was 3.4% (4 cases) versus the untreated site, which was 12.8% (15 cases), representing an almost four-fold increase. Alveolar osteitis (AO) was defined as loss of clot in the extraction site, severe pain refractory to narcotic intervention, and pain that radiated to the ear and preauricular area and was accompanied by a foul taste and odor. Also, the PRP- and PPP-treated sides showed better hemostasis at time of discharge, objectively faster soft tissue flap healing, decreased swelling seven days postsurgically, and a subjectively lower level of pain on the Visual Analog Scale of 1 to 10 (VAS), with an average of 3 on the PRP side and 6 on the untreated side. Finally, one-month follow-up Panelipse radiographs 40

demonstrated subjectively more dense bone fill and radiopacity in the extraction site of the PRP-treated side. Conclusion: PRP is an inexpensive and widely available modality to minimize the occurrence of AO and enhance both hard and soft tissue healing potentials. The clinician’s ability to utilize the known properties of transforming growth factor beta (TGF-␤) and platelet derived growth factor (PDGF) contained in the PRP preparation has dramatically changed our understanding of bone healing and physiology as well as improved the expected outcomes in both minor and major oral and maxillofacial surgery. References Marx RE, Carlson ER, Eichstaedt RM, et al: Platelet-rich plasmagrowth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:638, 1998 Tayapongsak P, O’Brien DA, Monteiro CB, et al: Autologous fibrin adhesive in mandibular reconstruction with particulate cancellous bone and marrow. J Oral Maxillofac Surg 52:161, 1994 Marx RE, Ehler WJ, Peleg M: Mandibular and facial reconstruction: Rehabilitation of the head and neck cancer patient. Bone 19:595, 1996 (suppl 1) Marx RE: Clinical application of bone biology to mandibular and maxillary reconstruction. Clin Plast Surg 21:377, 1994

BMP-Induced Heterotopic Bone Formation in Fetuin-Deficient Mice Brian Rittenberg, DDS, University of Toronto, Faculty of Dentistry, 124 Edward Street, Toronto, ON M5G 1G6 Canada (Clokie CML; Baker G; Tenenbaum H; Dennis J) Purpose: The use of bone morphogenetic proteins (BMP), instead of autogenous osseous grafting, to replace lost bone has been the focus of much investigation. However, it is difficult to regulate the extent and shape of BMP-induced bone and therefore regulatory approaches must be found. Similarly, heterotopic ossification is a major complication of total joint arthroplasty where endogenous BMP may play a role in initiating this problem. Together these issues suggest the need for a better understanding of the regulation of BMP-induced bone formation. Fetuin, also known as alpha2-HS-glycoprotein (Ahsg), is a serum and bone resident glycoprotein that binds to TGFbeta and BMP cytokines. It inhibits dexamethasone-induced in vitro osteogenesis, most likely by acting as a decoy receptor for TGFbeta, and BMP. We hypothesized that BMP-induced osteogenesis in vivo would be enhanced in Ahsg-deficient animals. Objectives: To demonstrate whether or not BMP-induced bone formation would be altered in Ahsg-deficient (Ahsgminus/minus) mice as compared to either heterozygous (Ahsgplus/minus) or wild-type (Ahsgplus/ plus) mice. Methods: Twelve mice from each group received 5 mg of human BMP/NCP in a 25% pluronic F-127 carrier AAOMS • 2003

Oral Abstract Session 2: Maxillofacial Pathology/Anesthesia/Maxillofacial Reconstruction/Orthognathic Surgery within a gelatin capsule via surgical implantation into the hindquarter muscles under anesthesia. Animals were sacrificed at 4 weeks. Two legs of the experiment took place, and a total of 72 animals were used. Radiography, bone density scanning (DEXA), and histomorphometric analyses were performed to demonstrate and quantify bone formation. Additionally, biochemical analyses for alkaline phosphatase (AP), a marker for bone cell differentiation, were performed on explants from the hindquarter muscles. Results: Bone mineral content (BMC) and ossicle area were significantly higher in Ahsgplus/minus versus Ahsgplus/plus mice (P ⬍ .05, ANOVA, Scheffe), while the bone mineral density (BMD) was significantly higher in the Ahsgplus/plus mice versus Ahsgminus/minus and/or Ahsgplus/minus mice (P ⬍ .01, ANOVA, Scheffe) when assessed using DEXA. Alkaline phosphatase levels were found to be significantly higher in Ahsgminus/minus mice versus Ahsgplus/minus and/or Ahsgplus/plus mice (P ⬍ .05, ANOVA, Scheffe). The ratio of cortical to cancellous bone was significantly higher in Ahsgminus/ minus mice versus Ahsgplus/plus mice (P ⬍ .05, ANOVA, Scheffe). Finally, a significantly higher incidence of satellite ossification was shown in Ahsgminus/ minus mice as compared to Ahsgplus/plus mice (chisquared, Bonferroni, P ⬍ .05). Conclusions: As parameters of osteogenesis were elevated in Ahsg-deficient animals, we suggest that, as it does in vitro, Ahsg may downregulate BMP-induced bone formation in vivo and could be used to control BMP-induced osteogenesis and possibly to inhibit pathological heterotopic bone formation. References Demetriou M, Binkert C, Sukhu B, et al: Fetuin/alpha2-HS glycoprotein is a transforming growth factor-beta type II receptor mimic and cytokine antagonist. J Biol Chem 271:12755, 1996 Paramore C, Lauryssen C, Rauzzino MJ, et al: The safety of OP-1 for lumbar fusion with decompression: A canine study. Neurosurgery 44:1151, 199 Funding Source: Ontario Research and Development Challenge Fund.

Simultaneous One Stage Implant Placement and Bone Grafting With Zygomatic Bone–A Prospective Study of 32 Consecutive Patients Vesa T. Kainulainen, DDS, Faculty of Dentistry, University of Oulu, PO Box 5281, Oulu, 90014 Finland (Sandor GKB; Carmichael RP) Objective: The aim of this prospective study was to evaluate particulated zygomatic corticocancellous bone grafts used simultaneously with one stage dental implants to reconstruct edentulous resorbed alveolar AAOMS • 2003

ridges, especially with regard to the bone augmentation obtained, implant osseointegration, donor site morbidity, and patient discomfort during the postoperative healing phase. Methods: A total of 32 patients were operated using particulated bone grafts simultaneously with one stage dental implants, in whom 82 implants were placed. Bone grafts were required for 72 of these implants. In all cases bone was harvested using a new surgical procedure and a new donor site, zygomatic bone. The bone graft was harvested from the zygoma using a custom-made bone collector. The volume of the bone graft obtained was measured. Local anesthesia with sedation was used in 27 cases and general anesthesia in 5 cases. Possible intraoperative complications were recorded. Morbidity and complications were recorded on follow-up visits. Implant success and outcome of the bone grafts were examined prospectively. Results: As a harvest site, the zygoma yielded sufficient quantities of bone to complete the required reconstructions in all 32 cases. In one case bone was harvested bilaterally. The average zygomatic bone graft volume was 0.90 mL (SD 0.30). Maxillary sinus perforation occurred in 11 zygoma sites. None of these patients had any postoperative problems due to the perforation. No paresthesias or other complications were noted during follow-up examinations. Mean duration of postoperative swelling was 4.5 days and patients used pain medication (acetaminophen 500 mg with 30 mg of codeine) for a mean time of 4 days. After the follow-up period of 8 to 20 months (mean 17 months), 80 of 82 implants achieved successful osseointegration (97.6% success rate). None of the bone grafts were infected or lost during the healing period. Conclusions: Zygomatic bone is a safe intraoral harvesting donor site. The outcome of particulated zygomatic bone grafts and simultaneously placed one-stage dental implants in a prospective clinical study was excellent. References Kainulainen VT, Sandor GKB, Oikarinen KS, et al: Zygomatic bone– an additional donor site for alveolar bone reconstruction: A technical note. Int J Oral Maxillofac Implants 17:723, 2002 Kainulainen V, Oikarinen K: Comparison of four bone collectors designed for oral and maxillofacial surgery–an in vitro study. Clin Oral Implant Res 9:327, 1998

Funding Source: University of Oulu.

Ridge Augmentation With PRP/PPP and Mineralized Bone in Dogs Matthew E. Dudziak, DDS, LSU School of Dentistry, 1100 Florida Avenue, New Orleans, LA 70119 (Block MS) 41