INFUSE BONE GRAFT IS A SAFE, EFFECTIVE ALTERNATIVE TO AUTOGRAFT
Clinical study information provides detailed data on the effectiveness of Infuse™ Bone Graft for oral-maxillofacial surgery. With more than a decade of clinical use, recombinant human bone morphogenetic protein 2 (rhBMP-2) has become one of the most extensively researched biologic agents commercially available today.
Infuse Bone Graft has over 10 years of approved market utilization and remains a safe and efficacious alternative to harvesting an individual’s own bone. Infuse Bone Graft has gone through the most stringent pathway for approval as a Class III Device with the U.S. Food and Drug Administration.
Infuse Bone Graft has a well-defined safety profile — without the possible pain and bone graft complications associated with bone harvest procedures.
CLINICAL RESULTS: VIABLE BONE INDUCED WITH INFUSE BONE GRAFT1,2
Infuse Bone Graft was studied in a clinical program that included 312 patients who received either a sinus augmentation or localized alveolar ridge augmentation. In these investigational device exemption (IDE) clinical trials, the participants received either autograft or Infuse Bone Graft, and they were followed for an average of three to five years depending on the study.
SINUS AUGMENTATION PROGRAM
The sinus augmentation clinical program included 220 patients enrolled in the sinus augmentation clinical program over four studies. This included:
- Pilot study of 12 patients at four sites treated with Infuse Bone Graft3
- Two consecutive randomized, controlled, multicenter trials:4
- Six centers participated in the first 48-patient trial.
- 21 centers participated in the second 160-patient trial, two-year postfunctional loading.
- 99 patients received Infuse Bone Graft, two-year postfunctional loading follow-up.
Infuse Bone Graft Consistently Forms Bone in Sinus Augmentation Study
The sinus augmentation studies demonstrated that Infuse Bone Graft consistently and predictably forms bone.4 Ninety-eight out of 99 patients in the sinus augmentation randomized controlled trials (RCTs) who received Infuse Bone Graft grew new, viable bone. The patient who did not grow bone had a chronic infection and failed a subsequent autografting procedure.
An average of 8.2 mm of mature, viable bone was induced with the use of Infuse Bone Graft, resulting in an average of 13.8 mm of total bone for implant placement. Patients received multiple implants per sinus, some of which were placed into sites with greater than 6mm of native bone due to anatomical configuration.
LOCALIZED ALVEOLAR RIDGE AUGMENTATION PROGRAM3
The localized alveolar ridge augmentation clinical program included three studies of 92 patients who had 50% or greater buccal wall defects in extraction sockets. The studies included:
- Pilot study of 12 patients at two sites treated Infuse Bone Graft
- Randomized, controlled, multicenter trial:
- Eight centers participated in the 80-patient trial
- 21 patients received Infuse Bone Graft
Adequate Localized Bone Formation in Alveolar Ridge Study
Infuse Bone Graft generates new bone of adequate dimension that permits placement of dental implants that can be used to support fixed dental prostheses.
HISTOLOGY SHOWS INDUCED MATURE, VIABLE, AND VASCULAR BONE
Bone core samples were taken at the time of dental implant placement in the RCTs. Core biopsies were acquired as early as six months post-Infuse Bone Graft placement and as late as 15 months. The bone formed in both the localized alveolar ridge augmentation and sinus augmentation studies was found to be similar. Infuse Bone Graft induces new, mature, viable bone with a rich vascular marrow space. Autogenous bone graft induced viable bone but the bone quality of the core samples was variable and included nonviable bone.
At the time of biopsy, the bone formed by Infuse Bone Graft was mature, primarily lamellar bone. Active remodeling was ongoing in the bone as it continued to grow and mature:
- Similar trabecular volume and thickness
- Both with 90–95% lamellar bone with small amounts of immature bone
The multicenter, randomized human clinical trials for Infuse Bone Graft included a histological endpoint. When our investigators placed the dental implant, they took trephine core biopsies from each grafting site. Trephine core biopsies of Infuse Bone Graft and autogenous bone grafted sites were judged by independent reviewers to be equivalent: Bone grafts grew normal bone with little or no residual material, regardless of the procedure studied.
DE NOVO BONE DENSITY INCREASES OVER TIME
Density measurements were taken four months post-bone grafting and at six months post-implant placement. Comparing the control group (autograft) to the Infuse Bone Graft recipients, both groups had developed dense bone.
- At 4 months, the autograft group had higher density (likely due to residual mineral density of the bone graft).
- At 6 months, the Infuse Bone Graft group had higher density (due to the normal maturation of 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.
INFUSE EQUIVALENT TO AUTOGRAFT OVER TWO YEARS POST-PROSTHESIS PLACEMENT
The primary effectiveness endpoint in the sinus augmentation IDE was to induce bone to successfully support implant-borne restoration after six months of functional loading. This endpoint was prospectively targeted at 73%, and was met—80% of the patients enrolled at 21 sites remain functionally loaded at six months, post-prosthesis placement.
The number of patients in the localized alveolar ridge augmentation study that had enough mature, viable bone induced for implant placement without augmentation was similar to the sinus augmentation study results (86%).
There was no significant difference in implant survival either by patient or by implant between the autograft and Infuse Bone Graft groups over two years post-prosthesis placement.
A total of 314 implants were placed in each group. The only failures that occurred during loading included:
- Five implants in the autograft group at six months
- Three implants in the Infuse Bone Graft groups at six and 24 months
BRIEF SUMMARY
INDICATIONS, CONTRAINDICATIONS, WARNINGS, AND PRECAUTION 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 consumers 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 consumers with any active malignancy or consumers undergoing treatment for a malignancy, in pregnant women, or consumers 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 consumers 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.
An electronic version of the package insert may be found at
1
Fiorellini et al. Randomized Study Evaluating Recombinant Human Bone Morphogenetic Protein-2 for Extraction Socket Augmentation, Journal of Periodontology 76: 605-613, 2005
2
Triplett 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, 2009 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 67:1947-1960, 2009
3
Data on File.
4
Boyne, P, De Novo Bone Induction by Human Bone Morphogenetic Protein-2 (rhBMP-2) in Maxillary Sinus Floor Augmentation, J Oral Maxillofacial Surgery 63: 1693-1707, 2005