Literature Comparison:
SteinerBio and NovaBone

With the realization that implant complications and implant failures are more common in augmented sites, dentistry is trying to understand why this is the case. Eventually, the profession will understand that implant complications and failures are not caused by augmentation, but by a specific type of graft material. As we have been saying for over 10 years, the dental profession is about to find out that the reason for many, if not most, of implant complications and failures is caused by the use of cadaver bone grafts and the sclerotic bone they produce.

As this knowledge develops, there will be a need to find an acceptable substitute and many dentists are now looking at the two leading science based synthetic bone grafts produced by SteinerBio and Novabone. Today we will review the literature comparing how these two materials produce bone in extraction sockets and sinuses. One feature regarding the studies performed is that they were both funded or produced by the companies that manufacture the products. This is unavoidable because all universities only study the current philosophy, which is cadaver bone grafts, leaving manufacturers to have to fund their own studies.

NovaBone in Extraction Sockets

We will start with NovaBone in sockets. NovaBone is PerioGlas (bioactive glass) with an inert binder to make it more manageable. PerioGlas is the original bioglass 45S5 developed in the latter part of the last century and began clinical use in 1985. PerioGlas was introduced to the dental market in the 1990s. NovaBone is composed of calcium-phopho-silicate particulate (PerioGlas) and an absorbable binder of polyethylene glycol and glycerin. NovaBone coined the term osteostimulation and claims the product is

“The only synthetic proven to signal genetic pathways to build strong bone fast.”
“Capable of signaling and recruiting osteoprogenitor cells the “stem cells” for bone.”
“The only bone graft substitute that controls the osteoblast cycle to favor proliferation and differentiation of bone-forming cells.”

Note that they claim that NovaBone stimulates the genetic pathway that builds strong bones fast, but they do not claim that NovaBone results in stimulating bone formation. Increasing the amount of bone produced is called stimulating osteogenesis, which requires a modification of the metabolic pathways that results in an increase in the amount of bone formed, which Novabone does not claim to do. If you take a culture of osteoblasts, preosteoblasts, or osteogenic stem cells that are deficient in calcium and phosphate, and you add elemental calcium and phosphate ions to the culture, you will “stimulate” the activity that NovaBone is claiming to stimulate. Without calcium and phosphate ions, the cellular process that makes bone cannot move forward, so adding calcium and phosphate simply allows cells to be “stimulated”. However, the normal human extracellular fluid is never deficient in calcium or phosphate ions and adding more does not result in more bone production.

While osteostimulation does not produce more bone, it does produce more sales. The problem with NovaBone claiming that it is osteostimulative by the release of calcium and phosphate ions is that the glass particles do not release relevant amounts of calcium and phosphate ions until bone forms around the particles and osteoclasts begin to resorb the particles as they release the ions. All resorbable bone graft granules will release calcium phosphate ions as they are resorbed, just like NovaBone, but because it does not result in more bone formation, no one else makes use of these marketing claims. If any graft materials should be considered to be osteostimulative, they would be SteinerBio bone grafts due to their composition. These bone grafts contain elemental calcium phosphate and calcium phosphate ions, which are incorporated into the bone during the process of bone formation (osteogenesis), not after bone has formed because then resorption of the particles have no value. However, lets allow the published research to determine what is marketing and what is science.

Dental implants placed in extraction sites implanted with bioactive glass: human histology and clinical outcome
March 2002 The International journal of oral & maxillofacial implants 17(2):249-57
Authors: Michael R Norton, DDS, June Wilson, PhD

Two types of bioactive glass (BioGran and PerioGlas) were utilized as an alloplastic grafting material. Bone cores were trephined out at the time of implantation and processed and examined to evaluate the tissue response under the light microscope. “There was an absence of new bone for all core samples harvested within 6 months.” The authors stated that clinically and radiographically the grafted sockets were radiopaque, but in actuality, the radiopacity was a result of unresorbed bioglass particles rather than bone formation. To support this finding, they cited a study done by Dr. Nevins et al at Harvard School of Dental Medicine that reported good clinical and radiographic results to periodontal surgery using Perioglas, but reported that histologically, there was minimal new bone formation limited to the most apical borders of the defects. “No signs of periodontal regeneration as defined by new cementum, periodontal ligament, and bone formation on a previously diseased root surface were observed. Although the clinical results are encouraging and radiographs evidenced radiopacities within the defects, histologic analysis revealed that as a periodontal grafting material, bioactive glass (Perioglas) has only limited regenerative properties.” (Human histologic evaluation of bioactive ceramic in the treatment of periodontal osseous defects Int J Periodontics Restorative Dent. 2000 Oct;20(5):458-67. M L Nevins 1 , M Camelo, M Nevins, C J King, R J Oringer, R K Schenk, J P Fiorellini)

The following is from the socket grafting study:

Studies that graft sockets and harvest core samples for implant placement are designed not to evaluate tissue response, but to determine implant success rates. In this study, after grafting with the bioglasses, a total of 40 Astra Tech dental implants were placed. The overall success rate at the end of the study was 88.6% for implants that were in function for a mean period of 29.2 months (22 to 24 months). The authors postulated that since no bone formation has occurred in the first 6 months, the initial implant integration is likely to have derived only from those areas where implants came into contact with native bone.

Socket grafting with calcium phosphosilicate alloplast putty: a histomorphometric evaluation
Compend Contin Educ Dent 2012 Sep;33(8):e109-15.
Authors: Lanka Mahesh, Maurice A Salama, Gregori M Kurtzman, Frederic P C Joachim

After extraction of the involved teeth, CPS putty graft was placed, and the sockets were covered with a collagen plug. Cores were taken from 20 patients for histological evaluation and implants were placed.

RESULTS: Histomorphometric analysis revealed an average vital bone content of 49.5 (±20.7). A residual graft content of 4.3% (± 7.8) was observed following a healing time of 4.9 (± 0.8) months.

These are findings you would expect from a graft material that facilitates bone growth. However, some of the same authors did the same study of evaluating bone growth in sockets grafted with NovaBone and published their findings two years later in 2014. There was no explanation as to why the study was redone by the same authors, but findings were significantly different as you will read in the next publication. For this study, there was no mention of the success rates of implants placed in the sockets grafted with NovaBone.

Histomorphometric Evaluation of a Calcium-Phosphosilicate Putty Bone Substitute in Extraction Sockets
March 2014 The International Journal of Periodontics & Restorative Dentistry 34(2):233-9.
Authors: Georgios A Kotsakis, Frederic P C Joachim, Stephen A Saroff, Lanka Mahesh, Hari Prasad, Michael D Rohrer

The objective of this study was to evaluate bone regeneration in 24 sockets grafted with a calcium phosphosilicate putty alloplastic bone substitute (NovaBone). A core was obtained from 17 sockets prior to implant placement for histomorphometry at 5 to 6 months post-extraction.

RESULTS: Histomorphometric analysis revealed a mean vital bone content of 31.76% (± 14.20%) and residual graft content of 11.47% (± 8.99%) after a mean healing period of 5.7 months.

These findings are similar to the finding for sockets that have not been grafted. 31% mineralization is minimal after 6 months, but it is in line with the amount of bone formed without grafting. These findings indicate NovaBone did not promote bone growth, but neither did it inhibit bone growth. The presented histology is as follows. Again, these studies are not designed to evaluate tissue response, but to evaluate implant success rates for the implants placed in the grafted sites. No mention is made of the implant success rates:

SteinerBio in Extraction Sockets

SteinerBio products are a combination drug/device and are the only bone graft materials the FDA has cleared to claim that it stimulates osteogenesis. For a bone graft to claim that it stimulates ostegenesis, it must prove that it results in more bone than is formed normally in humans in addition to proving that it modifies the metabolic pathways that results in more and faster bone formation. For the FDA to permit dental implants be placed in a site grafted with a material, the manufactures must show that the material is fully resorbed and produces normal bone. SteinerBio products are the only bone graft products that the FDA has cleared for implant placement in sites grafted with their bone graft material. These clearances were gained by the submission to the FDA with the findings presented in the following study:

The healing socket and socket regeneration
Compend Contin Educ Dent 2008 Mar;29(2):114-6, 118, 120-4 passim
Authors: Gregory Gene Steiner, Warren Francis, Ronald Burrell, Melissa P Kallet, Dainon Michael Steiner, Roslynn Macias

This study was performed in a private practice and included consecutive patients who presented to the practice that followed through with tooth extraction and socket grafting, followed by implant placement. The extractions and socket grafts were performed primarily by general dentists with no affiliation to the manufacturer or the study. No patients were excluded for any medical reason, smoking, or alcohol consumption. The graft material was Socket Graft by SteinerBio.

Findings with study histology to follow:

8 weeks after grafting with Socket Graft the sites presented with an average of 50% mineralization.
14 weeks after grafting with Socket Graft the sites presented with an average of 70% mineralization.
18 weeks after extraction and grafting with Socket Graft presented with an average of 90% mineralization.
26 weeks after extraction and grafting with Socket Graft with an average of 90 % mineralization.

The above mineralization percentages were averages found in sties biopsied at the respective time periods. No cases presented with no or minimal mineralization and no cases presented with inflammation. All 100 cases had implants placed, restored and then followed for three years in function. 100% of the implants integrated and 100% of the implants were still in function after 3 years of function.

8 weeks after grafting with Socket Graft
50% mineralized tissue

9 weeks after grafting with Socket Graft

13 weeks after grafting with Socket Graft

14 weeks after grafting with Socket Graft
70% mineralized tissue

18 weeks after grafting with Socket Graft
90% mineralized tissue

26 weeks after grafting with Socket Graft
90% mineralized tissue

SteinerBio vs NovaBone for Sinus Augmentation

Both SteinerBio and NovaBone have one human sinus augmentation study in the literature. We will review the NovaBone study first. This study was performed at Harvard university and paid for by a grant from NovaBone:

Human Histologic Evaluation of the Use of the Dental Putty for Bone Formation in the Maxillary Sinus: Case Series
J Oral Implantol (2012) 38 (4): 391–398.
Authors: David M. Kim, DDS, DMSc; Myron Nevins, DDS; Marcelo Camelo, DDS; Marc L. Nevins, DMD, MMSc; Peter Schupbach, PhD; Vinicius S. Rodrigues, DDS; Joseph P. Fiorellini, DMD, DMSc

Six healthy patients requiring a total of 10 sinus augmentations received sinus augmentations. The sinus augmentation was performed under local anesthesia with a mucoperiosteal flap elevated to expose the buccal wall of the maxillary sinus. The space was then filled with the dental putty in several increments and the window was covered with an absorbable collagen membrane.

FIGURE 1. (a) An oval osteotomy was made with piezoelectric surgery for patient No. 1b. The integrity of the Schneiderian membrane was preserved and elevated to the medial wall of the sinus to allow placement of the grafting material. (b) Decortication of the medial wall of the sinus cavity was performed with the piezoelectric surgery to promote angiogenesis. The space was then filled with the dental putty in several increments. (c) The dental putty was contoured to the most outermost confines of the lateral aspect of the maxilla.

FIGURE 3. (a) The surgical reentry at 6 months for patient No. 1b revealed incomplete resolution of the osteotomy site. (b) The surgical reentry at 9 months for patient No. 4a required complete removal of the grafting material due to soft-tissue ingrowth and failed sinus augmentation procedure. (c) The surgical reentry at 9 months for patient No. 1a revealed clinical dense bone with a small hole from the osteotomy site. (d) The surgical reentry at 9 months for patient No. 6 revealed dense bone at the osteotomy site.

The Table and Figures 3a through d provide the clinical observations at the time of 6- and 9-month reopening. In summary, 3 sites experienced complete failure (patient Nos. 2a, 4a, and 4b), 3 sites evidenced soft and immature bone (patient Nos. 1b, 2b, and 5), 3 sites appeared to have some resistance to the trephine (patient Nos. 1a, 3a, and 3b), and 1 site appeared to have dense buccal bone (patient No. 6). Overall, regenerated bone on the osteotomy site was soft and did not offer significant resistance to the trephine. For those patients who experienced complete failure, regrafting of the sinus using an alternative bone graft was performed.

Histologic evaluation: The ground sections of the biopsied cores revealed minimum amounts of bone trabeculation surrounded by an abundant array of irregular-shaped residual alloplastic particles embedded in loose connective tissue (Figures 4a,b and 5). Newly formed vital bone adjacent to areas of augmentation materials was rare; thus, osteoconductivity was limited (Figures 6a,b and 7). There were no signs of local inflammation. Histomorphometric analysis was not performed because of insignificant trabeculation of new bone.

FIGURE 5. A higher-power magnification of the 6- month specimen revealed only irregular-shaped residual alloplastic particles embedded in loose connective tissue. DP indicates dental putty; CT, connective tissue.

Authors quote:

“The findings of the present study unfortunately did not reveal sufficient evidence of bone formation. As a result, only 4 of 10 sites received dental implants due to soft-tissue ingrowth and inadequacy of bone trabeculation. Limited new bone formation was insufficient to support contact or distance osseointegration. Expanding the study from 6 to 9 months resulted in only 1 appropriately healed osteotomy site and did not accomplish the hopeful results.”
[Conclusion] “Our clinical and histologic results from the current study did not support the use of dental putty for sinus augmentation cases because of its limited osteoconductivity.

The following study involved sinus augmentation using the product, Sinus Graft by SteinerBio, previously marketed as “Regen Biocement”.

Minimally Invasive Sinus Augmentation
J Oral Implantol (2010) 36 (4): 295–304.
Authors: Gregory Gene Steiner, DDS, MS; Dainon M. Steiner, MS; Melis P. Herbias, MBA; Roslynn Steiner

A series of 30 implants were placed in 18 patients. Two of the patients were smokers. The number of cigarettes smoked per day was not documented. All patients were administered 500 mg amoxicillin by mouth for 7 days postoperatively. All sinuses were augmented using the Steiner Sinus Lift technique with Sinus Graft used as the graft material. The average age of the patient pool was 58 years, with an age range of 44 to 92 years. No screening was provided for various disease states or habits other than smoking and bruxism. A wide range of diseases were represented in the patient pool. No patients were excluded from the study for health reasons. The range of pre-graft alveolar bone was between 2.5 mm and 8 mm, with an average alveolar bone thickness of 4.6 mm.

Minimally invasive surgical methodology:

Figure 4. A No. 8 round bur is used to prepare the osteotomy. Figure 5. O indicates osteoid-like bone lining; M sinus membrane; B, bone. The micropaddle is approximately 1 mm in diameter. Figure 6. The micropaddle is used to dissect the sinus membrane in the immediate area of the osteotomy. Figure 7. After the micropaddle procedure, a microball is used to separate the membrane from the floor of the sinus until the medial wall of the sinus is reached. Figure 8. Regen Biocement (Sinus Graft) is injected between the sinus membrane and the alveolar bone. Figure 9. The graft material fills the posterior portion of the graft site on the left, but the sinus membrane remains attached in the mesial portion of the sinus to the right.

Figure 10. A low sinus in the molar region. Figure 11. The sinus has been grafted and pilot holes started. Figure 12. Three months after sinus lift and implant placement. Figure 13. Four months post grafting and implant placement with the implants restored. Figure 14. Clinical photograph of restored implants.

Figure 16. Root fracture on tooth #5. Figure 17. Root fracture defect with sinus lift osteotomy in white to left in the image. Figure 18. NB indicates new bone; OB, original bone. Figure 19. Seven months after grafting, 3 months after restoration. Figure 20. Seven months after grafting, 3 months after restoration. Figure 21. Bone core sample 15 weeks after sinus lift with Regen Biocement (Sinus Graft).

RESULTS: All 30 implants integrated, but 1 implant failed at 21 months. The single failure occurred in a patient with bruxism who wore a mandibular night guard. Over the time period of the study, the survival rate was 97%. All sinuses were grafted with Sinus Graft.

At the end of the study, the average time since placement was 16 months, with a range of 6 to 33 months. In 15 of the 18 patients, the implants were placed at the time of sinus grafting. For the three patients who received delayed implant placement, all buccal osteotomies were filled with dense mineralized bone. The core samples of the delayed implant placement showed an average of 50% mineralized tissue.

SteinerBio vs NovaBone: Literature Assessment

First, we would like to state that a thorough search of the literature was performed to find all relevant studies that evaluated the performance of SteinerBio and NovaBone in human sockets and sinuses. If we have missed any relevant human studies, please provide those and we will do an amended publication. Implant survival studies in sockets were limited to prospective studies of approximately 3 years duration or longer. No implant survival studies could be found of any duration for Novabone used for sinus augmentation.

Bone Mineralization and Implant Survival in Extraction Sockets

The first study (published in 2002) was performed by an independent practitioner claiming no financial support by NovaBone. In this study, no bone formation was found in extraction sockets at the 6-month time period for implant placement. The implant survival rate was 88% after 29 months. The second study cited for NovaBone in sockets (2012) showed a 50% mineralization after 6 months. However, the third study cited (2014) was identical to the 2012 study with many of the same authors, some of whom were consultants for NovaBone, and found that 6 months after extraction and grafting, the bone mineralization in the extraction sockets averaged 31%. So why would NovaBone commission two identical studies by the same authors?

Extraction socket graft studies that take core samples and place implants are designed to evaluate implant success rates, not bone formation. The patient pool is established and the implants are in place, so why would you not follow the patients for implant success rates? With two identical studies that graft extraction sockets and place implants, it is very easy to simply follow the patients and collect that data on implant success and failure. However, because there were no reports on the success of the implants, it is plausible that the data was collected but not reported. The independent NovaBone study on sockets grafted with NovaBone would have the most credibility, but it seems difficult to accept that Novabone (PerioGlas) would prevent any bone formation. To support their finding, this study referenced a Harvard study that found no bone formation in periodontal lesions grafted with NovaBone (PerioGlas). The three studies combined indicate that the most recent study (2014) performed under the supervision of NovaBone that produced 31% mineralization is the most accurate finding. 31% mineralization is equivalent to the mineralization found in non-grafted sites and this indicates that NovaBone has no stimulative properties on bone formation in sockets.

The SteinerBio publication was a manufacturer produced study, however, the findings for percent bone mineralization was regular and supported by core samples taken at the various time points that show that at 8 weeks sockets produce 50% mineralized tissue. The subsequent histology at longer time frames shows mineralization of 70% at 14 weeks and 90% at 6 months. Histology of normal woven bone with this degree of mineralization has never been published for any other grafting material and these findings were the basis for SteinerBio products being the only graft materials permitted by the FDA to claim that they stimulate osteogenesis. With normal trabecular bone between 30 and 50% mineralized tissue, anything over that percentage shows that the graft material was responsible for stimulating osteogenesis. The bone found in these sockets has been proven to be normal bone by subsequent studies that have shown this bone to remodel when loaded into lamellar bone of normal architecture. The implant survival rate of 100% after three years that was found in this study supports the finding that the more vital the bone, the higher the implant survival and success rates.

Sinus Augmentation

The 2010 study using Sinus Graft for sinus augmentation produced predictable bone regeneration with an implant success rate of 97%. The histology showed an above normal level of mineralization and radiographic images showed a higher level of mineralization than the adjacent native bone irrespective of the fact that the entire graft material are completely resorbed in 2-3 months established that the radiopacity was due to a high level of vital bone formation and not residual graft particles.

The NovaBone sinus augmentation study was funded by NovaBone and performed at one of our elite universities by experienced surgeons. The protocol was for delayed implant placement at 6 months after sinus grafting with NovaBone. The healing was so poor that after three patients were surgically opened at 6 months, the study was delayed for another three months to allow for more healing. The additional time did not improve the results. The authors state that only 4 of 10 sites received an implant due to failed grafts. No histolomorphological analysis was performed on the core samples because there was not enough bone to evaluate the percentage of bone at any time frame. The authors concluded that NovaBone should not be used for sinus augmentation grafting. The maxillary sinus is one of the easiest areas of the body to grow bone. The summation of the studies presented on NovaBone indicates that NovaBone is not osteostimulative or osteoconductive, but may possibly be osteoinhibitive. SteinerBio products showed above normal bone formation and excellent implant success rates to indicate that stimulating osteogenesis provides a higher level of bone vitality resulting in a higher levels of clinical success.

With the results of the NovaBone studies, it is easy to understand why academics turned away from synthetics and embraced cadaver tissues. However, science has marched on while cadaver tissue has not and it is time for academics to re-evaluate science-based synthetics.

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Literature Comparison:
SteinerBio and NovaBone

MEMBER:

866.317.1348

contactus@steinerbio.com

Literature Comparison: SteinerBio and NovaBone

MEMBER:

Literature Comparison:
SteinerBio and NovaBone