An occasionally irregular blog about orthodontics

Lets talk about micro-osteoperforation….

Lets talk about micro-osteoperforation….

Lets talk about micro-osteoperforation….

At a recent conference I was discussing “ways to make teeth move faster”.  After my presentation a delegate asked me about the evidence that underpinned micro-osteoperforation or MOPS.  So, let’s talk about MOPS/Propel…

The leaders in MOPS are Propel. I will start by looking at their website.  It is small, compact and does not contain much information.  It shows that Propel has two main products.  One is the VPro5 this is an intra-oral vibrator that appears to be similar to AcceleDent but you only need to use if for five minutes a day. They market this device as an “aligner seater”. They do not provide any research that supports its use.

Their other product is called the Excellerator. This is a method of micro-osteoperforation and involves making small holes in the alveolar bone and speeding up tooth movement.  The only supporting evidence they provided was a paper published in the AJO-DDO in 2013.  I have posted about this paper before, but I am going to have another close look at it….

The papers that provide us with evidence

Effect of micro-osteoperforations on the rate of tooth movement

Mani Alikhani et al

Am J Orthod Dentofacial Orthop 2013;144:639-48

DOI: http://dx.doi.org/10.1016/j.ajodo.2013.06.017

In the introduction to the paper the study team point out that while the skill of the clinician and co-operation of the patient influence treatment duration, the main factor controlling the rate of tooth movement is bone biology.  They then put forward a theory that causing localised trauma to bone stimulates chemokines. This then leads to an increase in osteoclastic activity and rate of tooth movement.  They quote some animal studies in support of this claim.

A study on some rats that died….

I then had a look at the paper they quoted. This was published in the Journal of Dental Research and you can find it here.

They took 48 rats and fitted an orthodontic spring from the molar to the incisor. They then applied one of four interventions to the rats

  • Orthodontic force applied with no activation
  • Orthodontic force applied to spring
  • Orthodontic force applied and they raised a soft tissue flap
  • Orthodontic force applied, flap raised and they made several perforations of the alveolar bone

They evaluated the levels of various markers and chemicals. But I was more interested in tooth movement.  They only wrote one paragraph on this part of the study and they did not describe how they measured tooth movement, apart from writing that this was done after 28 days. They reported that the mean tooth movement for the orthodontic force group was 0.29mm and for the orthodontic force plus perforation it was 0.62mm.

Unfortunately, they did not provide any data on standard deviations or confidence intervals, they simply stated that they were significantly different.  We need to note that the effect size of the interventions is about 0.3mm/month. Importantly, they calculated this from a sample of only 12 rats in each group.

My feeling is that from this sparse amount of data they could not conclude with confidence that the rate of tooth movement was increased. So, not a great deal of evidence here.  Lets get back to the AJO paper…

What did they do?

They did a parallel group RCT with 1:1 allocation. They powered the study to detect a 50% difference in the rate of tooth movement.  I could not check this calculation because they did not give sufficient information.

The PICO was

Participants: Orthodontic patients 18-45 years old

Intervention: Micro-osteoperforation

Control: No intervention

Outcome: Rate of canine retraction measured from study casts.

They did not provide any details of randomisation, sequence generation and allocation concealment. This is a major deficiency in the paper and it results in the study being of high risk of bias.

I was also really confused about how they allocated the interventions and I had to work really hard to find out what they did.  I think that this is what happened…

They randomly assigned the patients to

  1. An experimental group who got MOPS on either the left or right side.  They randomised the sides, but they did not give any details on how they did this.
  2. The control group did not have MOPS.

They then compared the rate of tooth movement for the experimental group with the control group. They also carried out a comparison between the MOPS side and the non MOPS side in the MOPS group. In effect, they introduced a split mouth component into the study.  I have no idea why they took this step because it adds to the confusion and the difficulty of interpreting the data.

The residents providing the treatment were not blinded to the allocation. This is reasonable and understandable.

They took study casts at the start of canine retraction and 4 weeks later. The operator drew vertical lines on the palatal surface of the canines and measured the distance from these lines to the lateral incisor using digital calipers.  They carried out simple comparisons with the relevant univariate statistics.

What did they find?

20 patients completed the study. They illustrated differences between the groups using clinical photographs. They presented the tooth movement data using graphs and not as figures. As a result, I found it very difficult to interpret. I am not sure why they took this approach.  I have estimated this data (means and 95% CIs) from their graphs.

Interventionmm/28daysDifference
No MOPS0.5 (0.28-0.7)0.6 (0.52-0.76)
MOPS1.1 (0.8-1.32)

We now need to look at this data carefully. I worked out the following

The mean difference (effect size) is 0.6mm/month, when we look at the confidence intervals this shows that this difference could easily be from 0.5 to 0.7mm/month.  This means that there is high uncertainty in the data.  In spite of this uncertainty, the authors concluded that this intervention significantly increased the rate of tooth movement. They also state that MOPS could reduce treatment time by 62%. I have no idea how they reached this conclusion.

What did I think?

I really had problems understanding this study. I found their methods confusing because they used a combination of a 1:1 parallel trial and a split mouth study. Furthermore, I felt that the lack of clarity in the methods meant that this study is at high risk of bias.

I could also not understand why they used graphs and clinical pictures to present their data. We really need to see some numbers here.

I also thought about the effect size with respect to the normal rate of tooth movement.  It appears from the literature that the average rate of canine retraction is approx 1.1mm/month. This is similar to the rate that they detected in the MOP group in this study. In other words, the MOPS do not appear to speed up canine retraction when compared to the average rate.

Secondly, the effect size was only 0.6mm/month. This is not large and I cannot help wondering if this is worth the additional cost and hassle of MOPS.

Finally, I thought that their overall conclusion that MOPS could reduce treatment time by 62% was not supported by their data.

In summary, there are many issues with this paper that are not clear and I really wonder if it does provide evidence that Propel increases the speed of tooth movement.  It would be great to see larger scale studies into this treatment, as this technique may have potential.

Final thoughts

Currently, we only have one small study of 20 patients (at high risk of bias) and a study on some rats with no detail of how tooth movement was measured.  This should not be sufficient to adopt a new treatment.

As things stand we have to conclude that there is an absence of evidence that MOPS is effective….but lets continue promoting this form of untested treatment.

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  1. Anonymous says:

    One thing you forgot to mention is that the group that published the study is the group that licensed the patent of the device to propel.

  2. Kevin Kaiser says:

    It’s also a big flaw that they only followedthis group for 28 days. What happens over 3-6 months after the MOPsare done? Thank you for your detailed insight into this article!

  3. Vish says:

    Another major deficiency of the study was the lack of multiple data points. The lag phase of tooth movement can last up to 21 days. With a single measurement, it is impossible to speculate what the rate of movement would have been over the course of space closure. If there indeed was a clinically significant difference, how long does it last before needing another round of micro-osteoperforations?

  4. Anonymous says:

    And also the fact that these authors have sought to wrongly discredit any articles that have shown any potentially bad side effects of MOP – i.e. in the comment section in the most recent AJODO

  5. Anonymous says:

    An extreme form of MOPS is a recently complete extraction site. We know, at least based on clinical experience that teeth do move faster into extraction sites. Thus, at least in this extreme form MOPS works. Clinical research should focus on replicating this scenario and answering the following questions: Does it work in all ridge forms? Across all ages? How many osteoperforations are necessary per mm of ridge and at what diameter should the osteoperforation be completed?. Should the osteoperforations be completed parallel to the floor of the mouth or vertical into the ridge? Should the buccal and lingual plates be violated? How much more efficacious is MOPS compared to not using it. Only sound research with predictable results justifies the financial cost to the doctor and to the patient of an appliance like the one mentioned above. Most importantly, the benefits to the patient should clearly outweigh the risks of such procedure.

    Every time I read about the high frequency vibration of intraoral appliances, the ultrasonic unit I use in my practice comes to mind. This unit is very effective at dislodging foreign particles from the surface of instruments. As we know, cholesterol accumulates on the interior of the carotid arteries. We also know that disaster strikes in a form of a stroke when cholesterol plaques dislodge from the carotids. Thus a simple question comes to mind: Do these appliances have any effects on the carotids? Are there perceivable vibrations at the carotid level? Again, do the benefits of the intervention outweigh the risks?

  6. Thanks for bringing this topic to our attention again, Kevin. From a conceptual point of view, one has to ask the question, “Is it even possible to speed up tooth movement?” But let me re-phrase the question to, “Is it possible to speed up nerve transmission or any other physiologic process in the human body?” The key to the rate (velocity) of tooth movement and its subsequent acceleration, depends on the rate of bone remodeling, and the volume of bone which needs to be remodeled. Teeth are inanimate objects in the sense that they have no innate mechanism of movement. They are subject to gene-environmental interactions, including temporo-spatial patterning via the periodontium. So what does a tooth need to move? IMHO, the orthodontic profession is obsessed with force, presumably because (traditional) orthodontics developed in an era of Newtonian physics. Now, we have quantum physics and quantum biology (the human genome). I believe a tooth needs three things to permit movement: space; signal; guidance. The space in this sense is the functional space of the (mal)occlusion, including the 3D bone morphology. The signal e.g cyclic, intermittent, ultra-light forces are reduced via signal transduction to evoke sutural homeostasis within the periodontium. The guidance is provided by the various (fixed) appliances, aligners or other devices inadvertently e.g. sleep appliances and TMJ orthotics. My concept is summarized as the Spatial Matrix hypothesis (Craniofacial Growth Series, University of Michigan). Bottom line if you want a tooth to move faster, I believe you need to provide space (increase bone volume); signal (spatial and intermittent signaling) and guidance (a device/protocol that works well in your hands).

  7. CTOR says:

    Dear Kevin,

    We thank you for your interest in our research.

    It seems that you have been following our research for some time and we have seen similar iterations of your critiques and analyses in your previous blog posts.

    At the Consortium for Translational Orthodontic Research (CTOR), we follow a systematic protocol of translational science. Science, simply for the sake of it with no direct clinical application is not our goal. The animal study published in JDR was the prelude to the clinical study. Prior to publication, the results of this study were presented in a poster at the AAO Annual Meeting in 2010 and won first place in the Basic Science Category for the Charley Schultz Award. With the results of the animal study, we were guided in our design for the human clinical trial. The methodology for our research is sound and perhaps it would be prudent for readers to read it carefully. In the systematic review by Gkantidis et al (2014) https://doi.org/10.1016/j.jdent.2014.07.013 our 2013 human clinical trial was scored using the Cochrane Risk of Bias Assessment and scored lowest risk of bias in five categories, no high risk of bias in any categories and unknowns in two categories (one of which is blinding which is unfeasible for operators in this style of clinical study), the only other “unknown” on “random sequence generation” would have been easily clarified if we were contacted.

    The underlying principles here are to further understand the biological basis for tooth movement and how we may modulate biology to accelerate tooth movement. So yes, the evaluation of “various markers and chemicals” is as important as the measurement of tooth movement. Any efforts to move our specialty to the forefront of science have to be backed by clear and sound scientific reasons and principles lest we fall back into the dark ages of empirical dentistry.

    This has nothing to do with Propel or any company. Instead, this is about the globally accepted and basic principle in bone biology that trauma to bone induces inflammation (as measured by inflammatory markers), which then activates osteoclasts, thereby increasing local osteopenia, which (if done properly and controlled in the direction of tooth movement) facilitates orthodontic tooth movement. A key component of this principle is the direct relation of each step to the next. Thus, procedures such as corticotomy and piezocisions routinely cause more trauma than MOPs, thereby causing more visible tooth movement. However, MOPs are far less invasive than corticotomy or piezocision, making this approach to accelerated tooth movement both far more comfortable and safer for the patient and easy to incorporate in orthodontic treatment. Moreover, because MOPs is minimally invasive, the procedure can be repeated when necessary during treatment, allowing clinicians to “apply” inflammation as needed for the tooth movement so desired. Compare this level of inflammatory control to the the exorbitant inflammation induced by a single round of corticotomy or piezocision treatment, and it is clear that MOPs provides the customized, targeted control of inflammation that most benefits the patient.

    While it has been shown multiple times that corticotomy and peizocision facilitate tooth movement, peizocisions and MOPs share at least one feature. Each allows the clinician to precisely control the number, location and depth of the perforations. This “customization” feature allows the clinician to control the level of the trauma produced at each visit. If you induce little trauma the effect would be small and may clinically difficult to observe at the first post-treatment visit. But, if you repeat the minimally invasive treatment every month you will gradually accelerate bone remodeling along the path of tooth movement. Similarly, if you induce too much inflammation, the effect will be closer to that of corticotomy.

    What we are discussing here is science that can be traced to any bone biology text. When it comes to determining what is best for our patients, our personal views and biases are not only utterly irrelevant, they block progress and innovation. The specifics of companies, patents or tools do not matter to the patients. They want innovations that provide safe, efficient, minimally invasive treatment. This can only be achieved by scientists who let their deep understanding of science – rather than their ego and biases – guide their research and development programs for clinical benefits.

    We will not enter into a debate on science with you as this is clearly not a suitable platform, but you walk a precarious path when you fail to acknowledge the commendable work and efforts of your fellow scientists, researchers and academics. When you stand behind your electronic bully pulpit to conveniently denigrate scientists and their work – without sufficient data to back your accusations – you are taking the low road. This not only does little to advance the science in our profession, but it gives the impression that we are a field divided. We all want what is best for our patients, and while we would like to give you the benefit of the doubt and say that perhaps you truly care about the quality of the science that will make this possible, your frequent smugness when harshly criticizing other researchers’ work betrays your cynicism. The last thing that science, in general, and Orthodontics, in particular, needs is a new generation of researchers branded with your cynicism.

    Kindest regards,
    CTOR
    http://www.orthodonticscientist.org

  8. Kevin O'Brien says:

    Thank you for your comments on my blog posting. I am not really clear who I am replying to. It would be great if you could put your names to your comment? Can you also declare that you have no conflict of interest either personally or the University that you work for?

    I will happily deal with your comments.

    Firstly, my blog posts are based on my interpretation of the papers that I review and I do all that I can to be consistent. You are correct that I carry out a critical appraisal, however, this is no more harsh than the average journal club presentation.

    You seem to suggest that I was too critical of your paper. I leave this to readers to decide. I do think that when new invasive methods of treatment are introduced the research should be of the highest quality. As a result, I stand by my criticism of lack of details in the paper, particularly on sequence generation and concealment and presentation of the data. Interestingly, this is supported by the systematic review that you quoted. It is usual when this is unclear that the reviewers contact the authors and I will ask the authors of the review to respond to this point. Nevertheless, I cannot understand why you did not make this clear in your paper?

    I think it is also important to point out that their conclusions on MOPS are similar to mine. They stated

    “The overall quality of evidence supporting this intervention is low”

    “Overall, the results should be interpreted with caution given the small number, quality, and heterogeneity of the included studies”

    As regards your last comments. I apologise if you feel that I am overly cynical and I certainly take this comment on board. However, I carefully evaluate the papers that I post about. I do not stand behind an electronic bully pulpit and I address these issues when I am lecturing and answering questions.

    Finally, I note that you do not want to debate this research, but maybe you could answer three questions? Do you really believe that this study with such a small sample of patients provides sufficient evidence for the claims being made about MOPS? Secondly, how did you do the sequence generation, allocation and concealment? Finally, where in this paper is the data that enables you to state that MOPS could reduce orthodontic treatment duration by 62%.

    I still stand behind my conclusion that we do not really know if MOPS works. Perhaps you will publish more research?..

    • WD says:

      Regional Accelerated Phenomenon is universally accepted. This blog is starting to lose alot of my respect. Alot of providers may agree with you on acelledent being bogus but universally trashing all forms of accelerated orthodontics is extreme. Coming from a third party, you do sound like a bully…

      • Kevin O'Brien says:

        Thanks for the comments. I am sorry that my blog is starting to lose your respect. However, I feel that I am not trashing all forms of accelerated orthodontics, I am simply interpreting the research papers that are published. I may have reviewed a few of these over the last six months, but this is reflection of the papers that are currently being published. There is currently a big ethical issue in orthodontics concerned with the selling of untested treatments to patients. I believe that we need to be honest with our patients and when a new treatment is developed and released it needs to be tested to the best of our ability. This is particularly important when the patient/parents need to pay for the treatment. Currently, the evidence for the effectiveness is lacking and I cannot see how people can ethically promote these treatments. You state that accelerated orthodontics is accepted, but this does not mean that it works. Do you really think that there is sufficient evidence to sell this treatment to your patients?

        Your final comment on me sounding like a bully really concerns me and I shall certainly look very closely at my posts to see what I can change. I will also take advice from colleagues on how this appears to them.

        Thanks for your comments.

  9. Prof Dave Singh says:

    I think the MOP folks make some good points. I don’t think Dr O’Brien is being harsh – the nature of scientific approach is the bastion of skepticism. However, in my last message I mistakenly used the word ‘faster’ instead of, say, ‘efficiently’. I mentioned that one requirement of moving teeth ‘efficiently’ is bone volume. The MOP folks have come up with an alternative solution – decreasing bone volume. This is somewhat similar to traditional orthodontics where, typically, premolar teeth and the unsung third molars are/were routinely extracted, thereby inducing inflammation with subsequent bone remodeling to permit tooth alignment. The upside of the MOP technique is perhaps the ability of the body to heal micro-fractures. But, both the traditional and these novel techniques induce inflammation, and that raises the ethical issue that Kevin alludes to. We know that inflammation, in any form, is detrimental for human health. Conditions associated with inflammation include hypertension, asthma, arthritis, diabetes, multiple sclerosis, senescence due to stem cell depletion, inter alia. The questions remain: Is it wise to induce inflammation in otherwise healthy people – and is there a way that the body might moves teeth physiologically, for example during normal growth and development, without resorting to the inflammatory process?

  10. Stephen Murray says:

    I enjoy the blog generally, and I enjoyed this article. I don’t think Kevin O’Brien is particularly harsh or cynical, and I don’t think he’s a bully.

    He does have an appropriately sceptic/skeptic approach to his reviews which is consistent with Null Hypotheses and the idea that substantial claims require substantial proof. He’s pretty consistent with this, and pretty systematic and objective- most of the reviews have the same format and the same criticisms come up. This is combined with a sense of humour that will be familiar to some people – including many that have seen him lecture – and I can see why some people feel it’s harsh. The comedy environment in his locality produced Peter Kay, Johnny Vegas, Caroline Ahern, Steve Coogan and his university isn’t that far from Bernard Manning’s Embassy Club. The musical environment is The Smiths, Tony Wilson, The Fall, Happy Mondays, Stone Roses and Oasis. For politics it’s Winston Churchill . You can expect the default setting here to be sarcastic.

    On the other side, it can be upsetting to put a lot of effort into producing a research paper and not get it accepted into a journal (certainly I’m speaking from experience, and it was probable that KOB was one of the people who has rejected at least one of my papers), so I can imagine it can be upsetting to get something accepted then criticised once it’s in the professional domain (that’s happened to me too, in real time at conferences where I presented stuff). But that’s what happens in the arena of ideas and ideas are potent things.

    Finally, apart from humour and the conventions of politeness, I think there are other international differences in orthodontics – the UK is hard to impress with new ideas and has been for decades and we probably know that by now. Most of the times I go to British Orthodontic Conference I get a take home message of “this didn’t work”, “there’s no evidence for that”, “no benefit here”, “no difference was found” and I get on the plane thinking “why do I bother?” Then I go to the AAO and feel much more optimistic. But if I have to buy some magic beans, I need to be convinced that they really will grow into a giant beanstalk- I don’t want to just see a photo of some that were grown earlier. If the beans are good, then I’m up for them, and I’d imagine so is he.

  11. Nikolaos Pandis says:

    I have read with interest this blog and I have the following comments to make:

    – The aim of research is to provide effective and safe therapies for the patients and at the same time to reduce waste which has a negative impact on society as a whole [1]. It is common for products to be introduced without thorough testing of their effectiveness. A recent study indicates that almost one-half of marketed orthodontic products have been found to be ineffective after their introductions implying research waste and the need for companies to have their products tested before introduction to the market by independent investigators[2].

    -Understanding the biology is important but, given the array of factors involved, a high-quality clinical trial is far more important in determining clinical effectiveness than isolation of various markers and chemicals.

    – I have read this trial some time ago because we also used it in a Cochrane review [3]and I remember that reporting was not optimal. I contacted the authors for clarifications and after several emails and a face-to-face request with one of the authors at the Moyer’s Symposium I received a response about the randomization which was not convincing to the point that we could rate this domain as low risk of bias. Given the uncertainty it was rated as unclear. The CTOR statement indicating that we did not contact the trial authors is not correct.

    – We also received mean values and standard deviations; however, I am not sure if what was sent were actually standard deviations or standards errors. The supplied sd values were very small and I assumed them to be standard errors, however the raw data were not supplied and we were not sure. We ended up using the provided sds as standard deviations in the meta-analysis. For this reason this trial received most of the weight in the meta-analysis. It would be great if the authors can supply the raw data.

    For example, some of the provided and more extreme values were the following:

    Experimental group ( Ortho + MOP): Incisal (1.27 +0.16), Middle (1.12+ 0.15), cervical(1.05 +0.13) and you can see that sds are close to 1/10 of the mean values whereas looking on tooth alignment from a number of studies the sd is common to be ½ or more of the mean values[4]. Using standard errors as standard deviations can have a significant impact on the statistical results, precision of the estimates, trial weight on meta-analysis and thus interpretation of the results.

    – Given the small sample size and the fact that only 3 trials were included in the Cochrane review meta-analysis the quality of the evidence according to GRADE [5] was low and it would have been very low if only the MOPS trial was used. It is not ideal to make treatment decisions based on a single small trial.

    – In conclusion, I think the jury is still out on the effectiveness of MOPS and I think we should wait for more convincing evidence. We all have our known and unknown personal biases and we all must lay our cards on the table in order to promote transparency and benefit our patients. As the CTOR feels so strongly about the effectiveness of MOPS, I would encourage them to publish more data accurately and transparently so that we can also be convinced and benefit our patients. Otherwise, as things stand it looks like a case of “have faith but doubt not”.

    References

    1. Al-Shahi Salman R, Beller E, Kagan J, Hemminki E, Phillips RS, Savulescu J, et al. Increasing value and reducing waste in biomedical research regulation and management. Lancet. 2014;383: 176–185. doi:10.1016/S0140-6736(13)62297-7

    2. Seehra J, Pandis N, Fleming PS. Clinical evaluation of marketed orthodontic products: are researchers behind the times? A meta-epidemiological study. Prog Orthod. 2017;18: 14. doi:10.1186/s40510-017-0168-y

    3. Fleming PS, Fedorowicz Z, Johal A, El-Angbawi A, Pandis N. Surgical adjunctive procedures for accelerating orthodontic treatment. Cochrane Database Syst Rev. 2015;6: CD010572. doi:10.1002/14651858.CD010572.pub2

    4. Pandis N, Fleming PS, Spineli LM, Salanti G. Initial orthodontic alignment effectiveness with self-ligating and conventional appliances: a network meta-analysis in practice. Am J Orthod Dentofac Orthop Off Publ Am Assoc Orthod Its Const Soc Am Board Orthod. 2014;145: S152–163. doi:10.1016/j.ajodo.2013.12.016

    5. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64: 401–406. doi:10.1016/j.jclinepi.2010.07.015

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