Maxillary Sinus Grafting FPO

Transcription

1 Infuse Bone Graft Maxillary Sinus Grafting FPO

2 Results of Maxillary Sinus Augmentation Using INFUSE Bone Graft Preoperative 3.9mm Baseline 6 Months Postoperative 16.0mm Total Height

3 Infuse Bone Graft Maxillary Sinus Grafting

4 Dental implants are only as good as the bone they re in. INFUSE Bone Graft promotes natural bone growth to give you long-term implant success. Nothing is as reliable for placing implants as a patient s own bone. INFUSE Bone Graft uses the protein rhbmp-2 to regenerate biologic bone, creating an ideal environment for osseointegration to occur. Some of the reasons to consider INFUSE Bone Graft include: Regenerates 100% vital, vascular de novo bone with no residual graft material remaining to destabilize bone formation Highly osteoinductive Eliminates the need for a second surgery to conduct bone harvesting Supported by Level 1 clinical evidence While many different grafting materials are used for sinus augmentation, it s important to remember that not all sinuses are the same. Many challenges may present themselves due to: Volume Size Ability to revascularize graft material Time required for bone regeneration and healing Nothing responds to these challenges like true biologic bone. With INFUSE Bone Graft, you ll have a foundation for implants that you can trust. In the following pages, we ll present a logical, data-backed explanation of why INFUSE Bone Graft will give you the results you need for sinus augmentation. We will review: Importance of vital, vascular bone in osseointegration Sinus augmentation for deficient bone volume Challenges of sinus augmentation The differences in graft materials How INFUSE Bone Graft (rhbmp-2) leads to vital, vascular bone formation Clinical data supporting the effectiveness of INFUSE Bone Graft in sinus augmentation

5 How Osseointegration Began In 1952, Swedish orthopedic surgeon and researcher Per-Ingvar Brånemark conducted an experiment in which he used a titanium implant chamber to study blood flow in rabbit bone. When it was time to remove the titanium chambers from the bone that had formed, he discovered that the bone had integrated so completely with the implant that the chamber could not be removed. Brånemark called the discovery osseointegration, which is defined today as the formation of a direct interface between an implant and bone. 1-2 INFUSE Bone Graft Maxillary sinus grafting 1 Osseointegration Defined The Prerequisites for Osseointegration in Native Bone 1,3 Primary stability of implant Provides initial mechanical support Vital, vascular bone Provides long-term biological support Adequate load Leads to adaptation of bone structure A Closer Look at Osseointegration A patient s own bone, with its naturally occurring cellular and vascular supply, provides the ideal environment for successful long-term osseointegration of dental implants. Native cancellous bone: Large area of implant surface exposed to bone marrow with ample vascularity and abundance of precursor cells for osteoblast differentiation Native cortical bone: Primary stability by direct bone-to-implant contact Native soft tissue:»» Adapts to abutment of immobile implant so that a functional barrier is formed coronally to the margin of the anchoring bone A patient s own bone, with its naturally occurring cellular and vascular supply (when uncompromised), provides the ideal environment for successful long-term osseointegration of dental implants.

6 2 INFUSE Bone Graft Maxillary sinus grafting Why Vital, Vascular Bone is Important to the Biologic Stages of Osseointegration 3 1. Formation of peri-implant clot. 2. Osteoblasts begin immature (woven) bone deposition on the bony walls and the implant surface. 3. Immature (woven) bone replaced by mature (lamellar) bone and often concentrated in areas where major forces are transferred from the implant to the surrounding bone. 4. Normal bone remodeling occurs in the newly formed bone. Active and ongoing process of osteoclastic resorption followed by deposition of lamellar bone.

7 INFUSE Bone Graft Maxillary sinus grafting 3 Wolff s Law and the Importance of Maintaining Bone Structure The process of bone formation and remodeling was first proposed in the 1890s by Dr. Julius Wolff and is known as Wolff s Law. It states that every change in the form or function of a bone, or the function alone, leads to changes in the bone s internal architecture and in its external form as a result of the stresses placed upon it. 2,4 Osteogenic Capacity FORM follows FUNCTION Native bone maintenance with functional load Native bone resorption without functional load When maxillary teeth are lost, the alveolar bone no longer receives physical stimulation and begins to resorb, leaving a space or defect in the bony structure as well as diminishing the related cellular and vascular supply. Sinus Augmentation for Deficient Bone Volume in the Posterior Maxilla Maxillary sinus floor augmentation enables dental restoration for patients with insufficient maxillary bone. After placing graft material underneath the sinus membrane, an osteogenic process is used to restore the maxillary bone to the required height. The osteogenic capacity of the sinus cavity the ability of the remaining host bone and vasculature to revascularize, consolidate, and remodel the graft material placed in the defect 5 can be diminished for many reasons, including: Pneumatization Patient comorbidities (age, disease state, etc.) Trauma When considering grafting sinus defects for dental implant placement, there are several parameters that should be considered 6 : Residual bone height, size, and volume Vascularity and cellularity Healing time

8 4 INFUSE Bone Graft Maxillary sinus grafting Not All Sinuses are Created Equally Anatomical Challenges in Maxillary Sinus Augmentation: 1. The volume, size, and location of the bony defect Successful sinus augmentation can be hindered if the dimensions of the maxillary sinus cavity are excessive. Insufficient bone formation may occur in sinus cavities with larger dimensions, or in cases where limited alveolar bone remains after tooth loss. 7 In a severely pneumatized sinus 5-6 : The lateral and medial sinus bony walls of the cavity are typically farther apart. The sinus bony walls thin from the anterior of the cavity moving toward the posterior region. The blood and cellular supply provided by the bony walls have a much larger area to traverse and fill to successfully consolidate a graft. New bone forms from the adjacent bony walls surrounding the graft site at a rate of approximately 1.5mm per month. Therefore, the size of the graft site and its dimension mediolateral and anteroposterior should be considered when determining the type of graft material to use. 6 As residual bone deficiency and the volume of the sinus cavity increase, osteogenic capacity is diminished, and an increased burden is placed on the bone-forming capability of graft material. 7-8 Subsequently, autogenous bone or a highly osteoinductive autograft alternative becomes clinically indicated Reference Plane: Anterior to Third Molar >8mm 4mm to 8mm <4mm Residual Bone Height Initial stabilization of implant or grafting of deficiency LESS CHALLENGING Initial stabilization of implant or grafting of deficiency MORE CHALLENGING

9 INFUSE Bone Graft Maxillary sinus grafting 5 Not All Sinuses are Created Equally continued Reference Plane: Anterior to First Molar Reference Plane: Anterior to Third Molar Location of Planned Implant Placement Distance between walls is narrower LESS CHALLENGING Distance between the walls is wider MORE CHALLENGING " The proportion of vital bone formation after sinus augmentation is inversely proportional to the bucco-palatal distance." 7 Gustavo Avila, DDS, MS, PhD Sinus Anatomy: Not All Sinuses are Created Equally 2. The vitality of residual host bone and its ability to revascularize the graft material The dense vascular network of the maxillary sinus plays a vital part in the healing and regeneration of bone after sinus augmentation. 6 This network diminishes after tooth loss, trauma, and/or with advancing age, thus resulting in diminished quality, capacity, and supply of the existing sinus bony walls and the blood and cellular supply (osteogenic capacity) that the bony walls provide. 5 Consequently, the osteogenic capacity of a defect diminishes, and an increased burden is placed on the bone-forming capability of graft material. 7-8 Subsequently, the use of autogenous bone or a highly osteoinductive autograft alternative becomes clinically indicated Effects of age, trauma, or tooth loss on maxillary vascularity 6 : The number and size of blood vessels decrease. As bone resorption increases, cortical bone thins, resulting in less vascularization overall. As the lateral wall thins, blood supply to the lateral wall and lateral aspect of a graft shifts to come primarily from the periosteum, resulting in compromised vascularization to the region. Blood Supply to Maxilla/Maxillary Sinus Cavity

10 6 INFUSE Bone Graft Maxillary sinus grafting Not All Sinuses are Created Equally continued 3. The time required for bone regeneration/graft site healing Because severe atrophy of the sinus cavity increases volume and an unfavorable vascularization of the maxillary alveolar process and sinus, healing time will be one to two months longer than normal. 5 In especially large maxillary sinuses that are associated with severe pneumatization of the maxillary alveolar process, more than 20cc to 30cc of grafting material could be required. Increased healing time may be required for proper vital bone formation in large sinus cavities; therefore, clinicians may consider allowing sinus cavities presenting large bucco-palatal distances to heal for extended periods of time (six months or more). 5 Inferior to Superior Dimension Anterior to Posterior Dimension Medial to Lateral Dimension Not All Graft Materials are Created Equally As osteogenic capacity diminishes, the reliance on a graft material to regenerate vital, vascular bone increases. 7 What to consider when choosing graft materials Sinus augmentation aims to restore the resorbed maxilla to its naturally occurring composition and function. It does this by regenerating vital bone, rich in marrow space and responsive to load allowing placement of immobile, stable implants and encouraging osseointegration for long-term implant stability. Unconsolidated Graft Material Consolidated Graft Material 12 Months Postoperative 24 Months Postoperative 9 Months Postoperative 18 Months Postoperative

11 INFUSE Bone Graft Maxillary sinus grafting 7 Not All Graft Materials are Created Equally continued Graft consolidation is the process of graft material being surrounded by and invested in newly remodeled bone and incorporated into the vital host vascular bed, followed by functional remodeling. This requires an ample supply of blood and osteogenic cells that deposit new bone onto a solid surface. A wide range of grafting materials have been used in maxillary sinus floor augmentation with varying degrees of success. 12 There are significant differences among technologies, including the materials used to make them, their mechanisms of action, the uses for which they are indicated, and even the level of evidence the U.S. Food and Drug Administration requires before they are marketed. Materials used include intra- and extraoral autogenous bone harvested from the patient, allogeneic bone, xenogenic bone, alloplastic materials, and combinations of these materials all ranging in their ability to consolidate successfully with a recipient bed to form bone through either osteoconduction or osteoinduction. 5 In pneumatized sinus defects, the osteogenic capacity is deficient, and special consideration should be given to the graft material used and its ability to regenerate viable, vascular bone for implant osseointegration. 13 Osteoconduction Creeping substitution Not cell specific Passive response Considerations When Choosing Graft Materials If bone filler material is applied in areas in which implants are to be placed later the material should preferably be resorbed along with formation of new bone or during remodeling, thus allowing the implants to be placed in vital bone alone. 13 Daniel Buser, DDS Osteoinduction Recruitment of bone-forming cells to the graft site Differentiation into osteoblasts Active response

12 8 INFUSE Bone Graft Maxillary sinus grafting The rhbmp-2 Mechanism of Action* of INFUSE Bone Graft Leads to Vital, Vascular Bone Formation** Chemotaxis (Recruitment of stem cells) Proliferation (Increased number of available stem cells) Differentiation (Stem cells turn into osteoblasts) Angiogenesis and Trabecular Bone Formation

13 INFUSE Bone Graft Maxillary sinus grafting 9 The first step is the migration of bone-forming cells into the area. This occurs through chemotaxis, the stimulation of cell migration in response to a chemical signal. Mesenchymal stem cells (MSCs) and osteoblasts from bleeding bone, muscles, and the periosteum infiltrate the rhbmp-2/acs implant. In vitro studies have shown that rhbmp-2 can stimulate the specific chemotactic migration of boneforming cells MSCs proliferate in the vicinity of the rhbmp-2/acs. In vitro studies have shown that rhbmp-2 can increase the proliferation of several pluripotent cell lines that are capable of differentiating into osteoblasts In vitro studies of rhbmp-2 support the fact that differentiation of MSCs into bone-forming osteoblasts plays an essential role in the induction of new bone. 21 By binding to specific receptors on the surfaces of the MSCs, rhbmp-2 causes them to differentiate into bone-forming cells. 20, 22 Preclinical studies have 16, 18, shown that rhbmp-2 can cause the differentiation of precursor cells into osteoblasts. rhbmp-2 Mechanism of Action Preclinical studies support the concept that de novo bone formation initiated by rhbmp-2/acs is a local, self-limiting process forming a predictable volume of bone. The ability of rhbmp-2 to induce new bone formation is dependent upon its concentration. Both the concentration of rhbmp-2 and the length of time it is present at the implant site are positively correlated with the rate of bone formation and the density of the resulting bone. 21 * Commonly accepted mechanism of action as determined by in vitro and animal in vivo studies. ** U.S. Food and Drug Administration. Summary of Safety and Effectiveness-INFUSE Bone Graft (P000054).

14 10 INFUSE Bone Graft Maxillary sinus grafting INFUSE Bone Graft is Proven to Induce Vital, Vascular Bone Formation in Deficient Atrophic Maxillary Defects Parameters and Results of the Sinus Augmentation Clinical Program: Parameters: Forty-six surgeon investigators participated in two consecutive randomized, controlled, multicenter trials. Dosing study: 6 centers participated in the first 48-patient trial 37 (each patient received 0.75 or 1.5 mg/ml rhbmp-2/acs, or autograft). Pivotal study: 21 centers participated in the second 160-patient trial, twoyear postfunctional loading 9 (each patient received 1.5 mg/ml rhbmp-2/acs or autograft). A total of 99 patients received INFUSE Bone Graft, two-year post-functional loading follow-up.

15 INFUSE Bone Graft Maxillary sinus grafting 11 INFUSE Bone Graft is Proven to Induce Vital, Vascular Bone Formation in Deficient Atrophic Maxillary Defects continued Results: Ninety-eight of 99 patients in the sinus lift randomized controlled trials (RCTs) who received INFUSE Bone Graft grew new, vital, vascular bone. The patient who did not grow bone had a chronic infection and failed a subsequent autografting procedure. An average of 10mm of mature, viable bone was induced with the use of INFUSE Bone Graft in planned implant sites with less than 6mm of native bone, resulting in an average of 13.4mm of total bone for implant replacement. In planned implant sites with less than 4mm of native bone, an average of 10.7mm of mature, viable bone was induced with the use of INFUSE Bone Graft, resulting in an average of 13.2mm of total bone for implant replacement. Preoperative 3.9mm Baseline Patients Had to Have at Least One Site with Less Than 6mm to be Included in the Study 20mm 18mm Average New Bone Average Native Bone 6 Months Postoperative 16.0mm Total Height 16mm 14mm Total Bone Height 12mm 10mm 8mm 6mm 4mm 2mm 0mm 10.7mm 2.5mm Sites with 4mm or less N=123 Baseline Preoperative New Bone INFUSE Bone Graft Clinical Results In planned implant sites with less than 4mm of native bone, an average of 10.7mm of mature, viable bone was induced with the use of INFUSE Bone Graft, resulting in an average of 13.2mm of total bone for implant placement. 16 Weeks Postoperative INFUSE Bone Graft Placement

16 12 INFUSE Bone Graft Maxillary sinus grafting INFUSE Bone Graft Induces 100% de novo Bone Formation The multicenter, randomized human sinus augmentation clinical trials for INFUSE Bone Graft included a histological endpoint. Bone core samples were taken at the time of dental implant placement in each of the grafted sites as early as six months after INFUSE Bone Graft placement and as late as 15 months. The core biopsies of the INFUSE Bone Graft sites and the autogenous bone-grafted sites were judged by independent reviewers. Results: There was 90% to 95% lamellar bone with small amounts of immature bone. New bone formation throughout the bluestained area Patients received tetracycline 30 days postoperative to label new bone formation yellow-green Viewed with fluorescence microscope to visualize new bone formation New bone formation (depicted in yellow-green) occurs throughout the area grafted with INFUSE Bone Graft

17 INFUSE Bone Graft Maxillary sinus grafting 13 INFUSE Bone Graft Regenerates Mature, Viable Bone with a Rich, Vascular Marrow Space Active Trabecular Network Formation Mineralized woven (immature) bone islands Osteoblasts form new bone bridges that connect all the individual woven islands into a woven trabecular network Active Remodeling Osteoclast Woven (immature) bone Lamellar (mature) bone Osteoblasts Osteoclasts are lining up to remove woven (immature) bone on the upper side Osteoblasts are forming the lamellar (mature) bone on the bottom INFUSE Bone Graft Clinical Results

18 14 INFUSE Bone Graft Maxillary sinus grafting INFUSE Bone Graft Regenerates Bone that Responds to Functional Loading INFUSE Bone Graft Vs. Autogenous Bone Graft Density at 4 Months Postgrafting Density (mg/cc) Density measurements taken four months post-bone grafting Dense bone had developed in both groups The higher density in the autograft group was likely due to the residual mineral density of the bone graft Autograft INFUSE Bone Graft FORM follows FUNCTION Density at 6 Months Post-Implant Placement Density (mg/cc) By six months post-implant placement, the bone induced by INFUSE Bone Graft became more dense than the autograftformed bone The increase in density was due to the normal maturation of INFUSE Bone Graft induced bone and a response to the load put on the bone (Wolff s Law) The results demonstrate that bone induced by INFUSE Bone Graft responds as normal physiologic bone when loaded 0 Autograft INFUSE Bone Graft

19 INFUSE Bone Graft Maxillary sinus grafting 15 The Importance of Osteogenic Capacity During Sinus Augmentation As osteogenic capacity decreases, the greater the level of performance required of the bone graft. As Osteogenic Capacity Decreases Contributing Factors: Volume of Defect Location of Planned Implant(s) Vascularity Comorbidities Residual Bone Height As Osteogenic Capacity Decreases Contributing Considerations: Factors: Ability to Regenerate Vital, Volume Vascular of Defect Bone Location Ability to of Revascularize Planned Implant(s) Site Ability to Vascularity Fully Consolidate Ability to Minimize Comorbidities Healing Time Residual Bone Height Considerations: Ability to Regenerate Vital, Vascular Bone Ability to Revascularize Site Ability to Fully Consolidate Ability to Minimize Healing Time Reliance on the Graft Material Increases. Reliance on the Graft Material Increases. Reasons to Consider INFUSE Bone Graft Human Histology Demonstrates Human that Histology Demonstrates Regenerates that 100% vital, vascular de novo bone Both Autograft and INFUSE Both Bone Autograft Graft and INFUSE Bone Graft Highly osteoinductive Regenerate Vital, Vascular Regenerate Bone. Vital, Vascular Bone. Responds to functional loading Autograft Autograft Supported by Level 1 clinical evidence Established clinical gold standard Established clinical gold standard eliminates need for second harvest surgery INFUSE Bone Graft INFUSE Bone Graft Proven alternative to autograft Proven alternative to autograft Summary

20 16 INFUSE Bone Graft Maxillary sinus grafting Headline INFUSE Bone Graft Powers a Patient s Own Vital, Vascular Bone Regeneration INFUSE Bone Graft is a proven alternative to autograft: Provides proven, predictable bone formation in sinus augmentation by combining the bone-generating power of rhbmp-2* with a proven carrier, an absorbable collagen sponge (ACS). Eliminates the need for a second bone harvest surgery. Supported by extensive research and clinical results, including 60 preclinical trials and five clinical trials. INFUSE Bone Graft leads to new bone formation** in the most challenging maxillary defects: Application of rhbmp-2/acs results in the induction of vital, vascular bone locally at the site of implantation. This process includes the attraction of the patient's own mesenchymal stem cells into the site, their proliferation, and specific differentiation into bone-forming cells (osteoblasts), thus reducing reliance upon adjacent osteogenic surfaces. The bone induced by rhbmp-2/acs remodels and assumes the structure appropriate to its location and function, as would be expected from host bone. * Commonly accepted mechanism of action as determined by in vitro and animal in vivo studies. ** U.S. Food and Drug Administration. Summary of Safety and Effectiveness-INFUSE Bone Graft (P000054).

21 INFUSE Bone Graft Maxillary sinus grafting 17 Headline Important Information About INFUSE Bone Graft INFUSE Bone Graft should not be used: In patients with a known hypersensitivity to rhbmp-2, bovine type I collagen, or any other components of the formulation In the vicinity of a resected or extant tumor In patients with any active malignancy or in patients undergoing treatment for a malignancy In patients with an active infection at the operative site In pregnant women INFUSE Bone Graft Portfolio Kit Configurations Item # Graft Volume INFUSE Bone Graft XX Small cc This product has not been tested in pregnant women to determine if it could harm a developing fetus. This product has also not been studied in nursing mothers. Women of childbearing age should not become pregnant for one year following treatment with the product. Women of childbearing age should be warned of potential risks to a fetus and should discuss other possible treatments with their doctor. INFUSE Bone Graft X Small cc INFUSE Bone Graft Small cc INFUSE Bone Graft Medium cc INFUSE Bone Graft Large cc INFUSE Bone Graft Large II cc Summary

22 18 INFUSE Bone Graft Maxillary sinus grafting Important Product Information BRIEF SUMMARY OF INDICATIONS, CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS FOR INFUSE BONE GRAFT FOR CERTAIN ORAL MAXILLOFACIAL AND DENTAL REGENERATIVE USES INFUSE Bone Graft is indicated as an alternative to autogenous bone graft for sinus augmentations, and for localized alveolar ridge augmentations for defects associated with extraction sockets. The INFUSE Bone Graft consists of two components recombinant human Bone Morphogenetic Protein 2 (rhbmp 2) placed on an Absorbable Collagen Sponge (ACS). These components must be used as a system for the prescribed indication. The bone morphogenetic protein solution component must not be used without the carrier/scaffold component or with a carrier/ scaffold component different from the one described in the package insert. INFUSE Bone Graft is contraindicated for patients with a known hypersensitivity to recombinant human Bone Morphogenetic Protein-2, bovine Type I collagen or to other components of the formulation and should not be used in the vicinity of a resected or extant tumor, in patients with any active malignancy or patients undergoing treatment for a malignancy, in pregnant women, or patients with an active infection at the operative site. There are no adequate and well-controlled studies in human pregnant women. In an experimental rabbit study, rhbmp 2 has been shown to elicit antibodies that are capable of crossing the placenta. Women of childbearing potential should be warned by their surgeon of potential risk to a fetus and informed of other possible dental treatments. The safety and effectiveness of this device has not been established in nursing mothers. Women of childbearing potential should be advised to not become pregnant for one year following treatment with this device. INFUSE Bone Graft has not been studied in patients who are skeletally immature (<18 years of age or no radiographic evidence of epiphyseal closure). Please see the package insert for the complete list of indications, warnings, precautions, adverse events, clinical results, and other important medical information.

23 References 1. Brånemark PI et al. Osseointegrated implants in the treatment of the edentulous jaw: experience from a 10-year period. Scand J Plast Reconstr Surg. Sept 1977;16(suppl): Brånemark PI. Osseointegration and its experimental background. J Prosthet Dent. Sept 1983;50(3). 3. Schenk RK, Buser D. Osseointegration: a reality. Periodontol. 2000; 70:22-35; Wolff J. Das Gesetz der Transformation der Knochen. Berlin: Hirschwald A. Published with support from the Royal Academy of Sciences in Berlin; English translation by Maquet P and and Furlong R. Berlin, Springer-verlag; Excerpt available at: charite.de/en/institute/julius_wolff/. 5. Jensen OT, ed. The Sinus Bone Graft. 2nd ed. Chicago: Quintessence Pub Co.; Misch CE, ed. Contemporary Implant Dentistry. 3rd ed. St. Louis: Mosby Elsevier; Avila G et al. The influence of the bucco-palatal distance on sinus augmentation outcomes. J Perio. Jul 2010;81(7): Soardi CM, Spinato S, Zaffe D, Wang, HL. 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The jumping distance revisited: an experimental study in the dog. Clin Oral Implants Res. 2003;14: Davies JE. Understanding peri-implant endosseous healing. J Dent Educ. 2003;67: Albrektsson T et al. Osteoinduction, osteoconduction and osseointegration. European Spine J. 2001;10(suppl 2): S96-S Albrektsson T et al. Osseointegrated titanium implants: requirements for ensuring a long-lasting, direct bone-to-implant anchorage in man. Acta Orthop Scandinavia. 1981;52: Schenk RK et al. Histologic and Ultrastructural Features of Fracture Healing. In: Brighton CT et al., eds. Bone Regeneration & Repair. Rosemont, Ill.: American Academy of Orthopedic Surgeons; 1994: Boyne PJ, James RA. Grafting of the maxillary sinus floor with autogenous marrow and bone. J Oral Surg. 1980;38: Tatum H Jr. Maxillary and sinus implant reconstructions. Dent Clin North Am. 1986;30:207.

24 Medtronic Spinal and Biologics Business Worldwide Headquarters 2600 Sofamor Danek Drive Memphis, TN Pyramid Place Memphis, TN (901) (800) Customer Service: (800) For more information visit The surgical technique shown is for illustrative purposes only. The technique(s) actually employed in each case will always depend upon the medical judgment of the surgeon exercised before and during surgery as to the best mode of treatment for each patient. Please see the package insert for the complete list of indications, warnings, precautions, and other important medical information Medtronic Sofamor Danek USA, Inc. All Rights Reserved. PMD /0112