Fake Puros Studies

When talking to dentists about what bone graft material they use, we often hear that they use Puros because it has the most scientific support. We smile and do our best to maintain our composure. The last thing we want to do is to embarrass a fellow dentist by challenging his understanding of bone graft science. So, what did in this article is look at a few papers on Puros that are often quoted in support of this material. When we ask for the scientific support for placing implants in sockets grafted in allograft, the following paper is commonly cited:

Three-year analysis of Tapered Screw-Vent implants placed into extraction sockets grafted with mineralized bone allograft. J Oral Implantol. 2005;31(6):283-93.

Abstract

With clinicians placing more dental implants, it is becoming increasingly important to maintain bone volume after tooth extraction. This article reports the results of implants placed into extraction sites grafted with particulate mineralized bone allograft (Puros). A total of 313 extraction sites were grafted with mineralized bone graft during a 36-month period. A total of 252 Tapered Screw-Vent dental implants were placed into the grafted extraction sites after a 4- to 7-month healing period. All reentries revealed a bony hard structure acceptable for osteotomy preparation. A total of 244 of these implants have been restored with fixed prosthesis and 6 with removable overdentures for a total of 250 loaded implants. A total of 6 implants failed, which required their removal (2 implants before load and 4 after loading), resulting in a 97.6% implant success rate. We conclude that mineralized human allograft placed into extraction sites is clinically useful to maintain bone volume. This material provided a bony hard structure acceptable for implant placement with good success rates.

Per the title, this was a three-year study and three-year studies are an acceptable minimum amount of time to evaluate the long term success of an implant procedure. The number of implants placed is also acceptable as a minimum number of implants followed for 3 years is 100. Having looked at the title and abstract, every dentist who cites this article feels they have scientific validation for placing implants in allografts. Unfortunately, most never read the actual study and virtually no one reads the articles referenced within the article to justify the validity of their statements.

Let’s start with a few statements made in the paper and the citations used as scientific support for those statements.

  • It is obvious from the beginning that this is not an article about allografts, but a promotional piece for Puros. The authors say that other allografts (not Puros) may be sterilized by ethylene oxide and this is a proven carcinogen. Do they tell you that ethylene oxide has not been used for allograft sterilization for a number of years? Of course not, because it is intended to mislead you into thinking Puros is safer than other allografts.
  • Next, they go on to condemn the use of alloplasts by citing a paper that documents poor performance of a bioglass using a study with no controls or comparison graft materials. Did they cite a paper where allografts performed better than an alloplast? Of course not, because all papers comparing allografts to beta TCP show the alloplasts performing equal to or better than the allograft.
  • When describing Puros, they state it “promotes rapid healing and remodels completely” and provide a citation in their list of supporting references. As we know this is a patently false statement, we were especially curious to see what scientific support they have for such a fraudulent claim. The citation imprudently given for this untrue statement is a lecture!
  • There is not a single publication on record of this lecture to be found. Furthermore, the authors of this paper never even saw this lecture, however, we are quite sure Puros was happy to provide this “proof” of their alleged “rapid healing and complete remodeling.” This laughable reference for a wildly inaccurate statement was used to dupe you into buying Puros.
  • The authors state that “in freeze-dried bone allograft all osteocytic lacunae are filled with osteocytes, and in some cases Haversion systems with a capillary center is found.” To support this bogus statement, they cite a histological paper where the histology itself is completely unreadable. What’s worse is their statement directly contradicts the authors’ own previously published research which also happens to be cited in their references. In their own cited paper they describe Puros as being “nonvital mature bone” and show a Puros particle without any osteocytes.

Here is the histology referenced by the authors. It shows a piece of dead Puros particulate that is non-vital and without osteocytes in the lacuna (yellow arrows) surrounded by sclerotic mineralized tissue (red oval) that is vital and has osteocytes in the lacuna. This histology shows exactly what is happening during the mineralization of allograft particles. The allograft particle produces an intense chronic inflammatory response creating sclerotic bone that covers the allograft particles and isolates it from the immune system. At that point, the chronic inflammatory response subsides. Once this happens, there is no further resorption or remodeling of the sclerotic bone and the cadaver graft particle remains encased in sclerotic bone forever.

So how can the authors make a statement that completely contradicts their own published research? The only explanation is that there are two parties writing this paper. One reporting the findings and the other promoting Puros.

The paper is filled with false statements supported by nonexistent studies, but now let’s look to see what was actually done in the study. All long-term studies list the time the implants have been in function. In an implant survival study, time in function is the only piece of usable information. In this case, you have a clear indication that it is 3 years and the success rate is 97%. But this is not what was done. If you read carefully you’ll see that what they actually did was to start the study in a private practice where the first day of the study was the day of the first extraction and ended three years later.

Yes, you read that correctly.

Day one of the 3-year study began on the day of the first extraction, not on the first day of each implant receiving a restoration. After each extraction, there was a waiting period from between 3 and 7 months before the implant was placed. After the implant was placed there was another waiting period of 3 to 6 months. They stated “analysis of the patients revealed a total of 313 extraction sites grafted with mineralized bone allograft during a 36 month period.” They also stated that “The implants placed in this study ranged from 6 to 32 months after loading observation.

That is physically impossible.

If the wait time is a minimum of 3 months and the time before loading is a minimum of 3 months, the longest time any implant could be in function is 30 months. While this is seemingly a minor point, it sheds light on the fact that the data cannot be trusted. Under their protocol, some implants were not loaded for a full year after placement. So this three-year study started the day that the first extraction was performed and ended three years after that date, and still they call this a three-year study. There is only one piece of data that would be of value in this study and that is the mean time the implants were in function. Although they had this data, they purposely omitted it because then they wouldn’t be able to claim this to be a 3-year study. Under their protocol, the mean time of the implants in function is likely to be around 1 to 1.5 years.

This “study” is often cited as legitimate scientific support for grafting sockets with allografts. Dentists read the title and abstract and are all misled to believe that they have a 3-year study with a 97% success rate. You need to ask yourself why would anyone plan such a foolish study. Personally, we do not think this was the study that was planned. It is our assumption that the authors planned to do a legitimate 3-year study, but cut it short because either the authors or Puros did not like what was happening to the outcome of their implants.

Here is another fake Puros study commonly cited to provide scientific support that allografts are resorbed and produce normal bone:

Subantral Augmentation With Mineralized Cortical Bone Allograft Material: Clinical, Histological, and Histomorphometric Analyses and Graft Volume Assessments. Implant Dent. 2016 Jun;25(3):353-60.

Histomorphometry

The biopsies showed a mean 43.76% of bone marrow, 40.16% of mineralized bone, and 16.59% of woven bone. The mean of residual particles was 0.047%.

The study cited the biopsies contained an average of 43.76% bone marrow. Right here you know the authors know nothing about bone and that is why they were likely chosen to do this paper. The maxilla and mandible have no bone marrow. Bone marrow is a specific type of tissue for generating blood cells and there is no bone marrow found in our jaws. The soft tissue in our jaw is called stroma.

Bone marrow as described by the National Cancer Institute: The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.

The image below is bone marrow histology not found in our jaws:

The paper also repeatedly states that cancellous bone has been formed with lamellar bone in the form of trabeculae. This is a completely false statement. Cancellous bone with trabeculae composed of lamellar bone are never formed when using cadaver bone grafts and their own histology even shows it. Their histology, while very poor in quality, is composed of Puros particles encased in sclerotic bone that they call woven bone. The low power histology is of such a poor quality that you cannot see all of the residual Puros particles and this is no doubt intentional.

This is histology of regenerated bone in the mandible 6 months after being loaded. These are trabeculae never seen in sites grafted with cadaver bone. The soft connective tissue is obviously not bone marrow. It is called stroma. The dental profession has to stop talking about bone marrow in the jaws. It is embarrassing and makes us all look stupid.

They go on to report that “40.16% of the tissue is mineralized bone and 16.59% of the tissue is woven bone.” Huh?

They obviously do not know that woven bone is also mineralized bone. Additionally, the woven bone they are referring to is actually sclerotic bone. So, what are they calling mineralized bone? What they call mineralized bone is never described in the article, but they do show one histological sample. The histologic sample identifies osteocytes. The bone they identify as woven bone has osteocytes with nuclei. However, the bone they are calling newly formed lamellar bone is not living bone because the osteocyte lacuna has no living cells. The histology shows an osteon that only exists in cortical bone. What they are calling new lamellar bone is actually a cortical Puros bone graft particle. Yes, what the authors are calling newly formed lamellar bone is actually the graft material itself but they do not know the difference between dead graft material and newly formed lamellar bone. In this article, they used Puros composed exclusively of cortical bone. This histology is cortical bone as identified by the concentric layers of lamellar bone with a central Haversian canal. The only lamellar bone in this histology is dead Puros bone. Dr. Craig Misch has used this paper in an attempt to confirm that allografts are resorbed and turned into normal bone. However, after some education he conceded that the histology presented was not newly formed lamellar bone as cited in the paper but was, in fact, residual allograft particles.

The following image is a schematic of a cortical bone osteon:

The following image was extracted directly from the publication. What they are calling woven bone has living osteocytes that are obvious. However, what they are calling newly formed lamellar bone is clearly a dead Puros particle. There are no living osteocytes. The concentric pattern of cement lines does not occur in cancellous bone, but only in cortical bone.

Here is another mind-numbing statement:
“At 18 weeks, histological analysis of 11 cases biopsied in the sinus, using a non-decalcified technique revealed that allogenic bone substitute (cortical particulates) was surrounded by newly formed bone tissue with a low percentage of residual particles…”

In the same sentence, the authors say the histology is composed of Puros particles surrounded by bone and then say there are virtually no remaining Puros particles!

The purpose of the article, and the reason it is cited, is to establish that Puros allografts are resorbed and converted into normal bone. However, the only piece of readable histology they published clearly shows what they claim to be newly formed lamellar bone is actually a Puros graft particle. The authors discuss how Puros is completely resorbed with the mean residual particles at 0.047%. Someone convinced the authors that a dead Puros particle was actually new lamellar bone so they could falsely discuss how Puros is resorbed and converted into normal bone when none of it is true. In the discussion, they compare their findings of only 0.047% residual particles to other allografts that have a much higher percentage of retained particles so you will be fooled into thinking Puros is better.

Again, like in the first article reviewed, it appears from their contradictory statements that the findings are reported and then modified by a second party to fit their narrative. In the first article, they are presenting proof of the long-term success of implants placed sockets grafted with Puros and the second article is designed to convince you that Puros is fully resorbed and converted into normal bone. Tragically, these fake Puros studies have been successful. They are commonly cited to argue that implants in allografts are successful and that allografts are resorbed and converted into normal bone. The most alarming thing about these papers is that they actually make it into print and no one in our profession has the knowledge to call out the false statements. Why? Because unfortunately, our profession is in fact largely ignorant of bone and bone graft histology. But the real reason these appallingly unscientific publications are published and never critically evaluated is because it fits our profession’s bias. Our profession needs something to support the use of these materials and dentists are willing to blindly accept and irresponsibly cite these completely misleading articles because they have no other scientific support for using an allografts.

Puros sells to the profession based on the contention that it is somehow superior to all of the other freeze-dried bone allografts. However, a study published by Dr. Brian Mealey, graduate program director and director of the Specialist Division in the Department of Periodontics at UT Health San Antonio School of Dentistry, establishes that there is no difference between Puros and freeze-dried bone allografts in dimensional ridge changes or the histology of the core samples:

Ridge preservation following tooth extraction using mineralized freeze-dried bone allograft compared to mineralized solvent-dehydrated bone allograft: A randomized controlled clinical trial.

J Periodontol. 2019 Feb;90(2):126-133. doi: 10.1002/JPER.18-0199. Epub 2018 Sep 19.

After having read the Puros studies, we found this study to be a pleasure to read. Very well done from start to finish. However, you are intentionally misled in the discussion. The following statement is a case in point:

“Several studies have shown that FDBA grafts can provide the necessary dimensional stability of the ridge and provide a scaffold for vital bone formation for dental implant placement.11–14,17

Dr. Mealey and company are discussing FDBA, yet they inexplicably cite the following article supporting the use of FDBA for implant placement:

Reference #17
Long-term stability of osseointegrated implants in augmented bone: a 5-year prospective study in partially edentulous patients. Int J Periodontics Restorative Dent. 2002 Apr;22(2):109-17.

This study has nothing to do with FDBA! It is a long-term study of implants placed in autografts! You are once again intentionally misled to believe there is support for placing implants in cadaver bone graft sites. The group quotes a paper from 2002 on the success rates of implants placed in autografts because they have absolutely no scientific support for placing implants in sites grafted with allografts.

It gets worse. Further on in the discussion, they get into their osteoinduction claims about allografts. Unsurprisingly, they offer zero references for these absurd claims because none exist. What does exist are studies that show allografts are not osteoinductive in humans, but they wouldn’t dare include those references. Dr. Mealey has been making claims about allografts being osteoinductive for years and 10 years ago we had had enough of these falsehoods so we contacted him about his statements. 

Here is his undoctored response from 10 years ago about these issues.

1. The issue of osteoclastic resorption of mineralized bone to release BMPs is an interesting issue that has minimal human evidence for support. Yes, we found some osteoclasts in our human FDBA samples, but they were few in number. It is certainly possible that our harvesting time point of 18-20 weeks post-implantation was too late to actually find many osteoclasts, but that is also just a theory.

2. As you know, induction studies are generally done in animal models, as such studies are not do-able in humans. I know of no such human studies, which is why our discussion of this issue was more theoretical than evidence-based.

– Brian Mealey, DDS

There it is.

Everything you have been taught about osteoclast resorption and osteoinduction is just theory with no scientific evidence. Dr. Mealey, you need to stop misleading the profession and admit that there is no evidence that allograft particles are ever resorbed after mineralization, and you need to stop claiming that allografts have any positive physiologic properties such as osteoinduction in humans. You also need to admit that there are no legitimate long-term studies of implants placed in sockets grafted with allografts and you need to stop placing implants in sockets grafted with these materials until there is scientific justification to do so.

The Bottom Line

Our profession has a woeful lack of understanding of bone graft biology. There is not one professor or lecturer that can tell the difference between woven bone and sclerotic bone. If any professor or lecturer wants to learn how to diagnose sclerotic bone, we would be happy to train them. We do not expect any calls any time soon, unfortunately. There is absolutely no scientific support for allografts resorbing and being converted into normal bone, yet every professor and lecturer believes it and as a result, every student of theirs believes it also. You may also believe these absurdities because you have been trained by someone who didn’t know any better. There are no legitimate studies on the long-term success of implants placed in allografts or Bio-Oss where you have an adequate number of implants followed in function for a minimum of 3 years. There is no proof that implants integrate into cadaver bone grafts.

Dentistry is a noble profession. We have worked very hard to win the public’s favor. However, many patients today are forced to accept a cadaver bone graft when 41% of the public rejects the material. Everything dentists are telling patients about these materials is false and we have no scientific support for placing implants in sockets grafted with these materials. If you are in a lecture hall, demand valid scientific support for what they are advising. If you are referring a patient and your specialist uses these materials, demand that they justify putting these materials in your patients and only accept a response commensurate with your education and training. “But this is what we always do” is not an acceptable answer — certainly not for the steep responsibility we carry as medical professionals. We have scientific proof that implants in sockets grafted with cadaver tissue produce marginal bone loss. We are convinced that the biggest reason for implant failure is implants placed in sockets grafted with cadaver bone grafts and when this becomes known to the public, it will be a serious blow to our good standing. Our ignorance about bone graft biology is hurting our patients and we need to educate ourselves now.

MEMBER:

American Society for Bone and Mineral Research (ASBMR)

Tissue Engineering and Regenerative Medicine International Society (TERMIS)

American Academy of Implant Dentistry (AAID)