Cervical ADR and Heterotopic Ossification

[Harrison]

A patient facing cervical ADR is concerned about this and other studies. I can't recall if I posted this one in the Article Library, but I have always been concerned about using keeled designs for cervical ADR or any that require significant disruption of the vertebral bodies. IMHO, this is why taking NSAIDs after cervical ADR is so important -- they can help slow down an agressive bone growth (healing) response.

When reading the study below, recall that these three different designs all require surgical manipulation of the cervical bodies, some more than others. Even the Bryan is a non-keeled design, but:

"“Once the disc has been safely removed in its entirety, the empty disc space is prepared by milling or shaping the endplates…”

The Mobi-C has a nifty cupped endplate to cradle the vertebral body to more uniformly distribute weight, but it has has some gnarly endplate teeth to anchor it to the vertebral bone.

I could argue (as a layman) that this study proves out what I've been saying for years: the less bone removed, the less chance of heterotopic ossification. However, this statement may be oversimplified to the point of being inaccurate; though the eventual conclusion may be correct. In the meantime, I'll stick with my non-medical opinion regarding keeled designs.

Any way, here's one of the recent studies:

Spine: 15 July 2010 - Volume 35 - Issue 16 - pp 1556-1561

Difference in Occurrence of Heterotopic Ossification According to Prosthesis Type in the Cervical Artificial Disc Replacement

Yi, Seong MD, PhD*; Kim, Keung Nyun MD, PhD*; Yang, Moon Sul MD*; Yang, Joong Won MD*; Kim, Hoon MD*; Ha, Yoon MD, PhD*; Yoon, Do Heum MD, PhD*; Shin, Hyun Chul MD, PhD

Abstract

Study Design. Retrospective study of the difference of heterotopic ossification (HO) occurrence according to 3 different types of prosthesis.

Objective. This study was designed to investigate the difference of HO occurrence according to different type of prosthesis.

Summary of Background Data. HO is defined as formation of the bone outside the skeletal system. Reported HO occurrence rate in cervical artificial disc replacement (ADR) was unexpectedly high and varied. But the influencing factors of HO in cervical ADR have not been elucidated well. The prosthesis-related factors for making difference of HO occurrence were investigated in this study.

Methods. A total of 170 patients undergoing cervical arthroplasty with the Bryan cervical disc prosthesis (Medtroic Sofamor Danek, Memphis, TN), Mobi-C disc prosthesis (LDR Medical, Troyes, France), and ProDisc-C (Synthes, Inc., West Chester, PA) were included. Cervical lateral radiographs obtained before and after surgery were used to identify HO. Occurrence rate, occurrence-free period, location, and grade of HOs were investigated according to the different prosthesis.

Results. Each prosthesis group included patients as follows: Bryan disc, 81 patients; Mobi-C, 61 patients; and ProDisc-C, 28 patients. Overall HO rate was 40.6% (69 of 170 patients). Each HO occurrence rate by prosthesis was as follows:

Bryan disc group, 21.0%;
Mobi-C group, 52.5%;
ProDisc-C group, 71.4%.

In the survival analysis, all patients showed 27.1 ± 3.7 months as the median survival. The Bryan disc group showed statistically longer survival (48.4 ± 7.4 months) than the other groups.

Conclusion. Occurrence of HO is an inevitable postoperative complication after cervical ADR. The occurrence rate of HO was higher than our expectation. Moreover, definite differences in occurrence rate according to the prosthesis type were identified by this study.

[tman]

I just read the same article - I think this has huge implications and further data needs to be gathered. Another caveat to the HO is the degree - from what I understand grade 1-2 no big deal does not disrupt ROM of discs but grade 3-4 does, which still occurs in relatively high numbers, ROM is affected and therefore ADD is a possible result and one can make the argument it is similar or the same as fusion.

[Marti in Benicia]

Hi Richard. Mulling over the Koreans' HO study and the ISASS presentation by the Korean doctors, I have a ton of questions that have come up. First, though, I concur HO happens in occasional patients; the question is the true frequency.

It looks like the ISASS presentation is based on the Korean study. Hence, it’s hard to say whether this report is a “red-herring” or a “red flag.”

· They’re only dealing with 35 patients – from Korea – from the pool of thousands of patients world-wide.
· How are they installing ADRs in this Korean hospital that’s different from other surgeons worldwide that may be causing this problem with the ProDisc-C and Mobi-C?
· Given the years and years the products have been on the market, why hasn’t this issue – at the cited rate of HO – surfaced before now?
· Why aren’t surgeons with experience with multiple ADR designs substantiating the claims?
· What correlation is there with the keel design (compared to the M6-C, which are more numerous but much smaller) and the problems the Koreas are having with HO?

At this moment, I’m more on the “red-herring” side until I can get answers to these, and my other, questions. STILL, this IS an issue that every ADR patient needs to factor in – “is this a potential risk I’m willing to take for my life quality?” – especially since every surgical implant has its inherent risks.


Two reports on one pool of patients does not make fact.

What are your thoughts?

Marti

[tman]

I read a study from eur spine journal - See below

Intermediate clinical and radiological results of cervical TDR
(Mobi-C
) with up to 2 years of follow-up
J. Beaurain Æ P. Bernard Æ T. Dufour Æ J. M. Fuentes Æ
I. Hovorka Æ J. Huppert Æ J. P. Steib Æ J. M. Vital Æ
L. Aubourg Æ T. Vila

this study had a cohort of 68 patients with 76 implants. 88% had grade 0,1,2 HO, 12% had Grade 3,4 HO. It also showed ADD although mostly minor in 9% of the cohort after 2 yrs. It would be nice to know what is the ADD after 10yr

The issue is how this HO effects ROM of the implant and does it lead to ADD.

[Harrison]

You both raise some excellent points and questions. Tman, you hit the nail on the head in terms of staging the actual degree of HO! What stage is it for the patients? Does it restrict ROM? What was the grade of HO for each group? Maybe this is mentioned in the full study, but this is clear as mud to me presently…

But here’s the net point from the study that is both controversial and potentially earth-shattering for us patients:

“…definite differences in (heterotopic ossification) occurrence rate according to the prosthesis type were identified by this study…”

Now compare this with other studies, and you will see that once again, we patients are TORTURED by a range of different studies with different conclusions!

Operational demographics and clinical results of 100 consecutive artificial cervical disc replacements
http://www.adrsupport.org/forums/f50...009-nov-10338/

Complications with cervical arthroplasty.
article (cervical)

This trend of varied study results is nothing new and it is the main reason why I put so much thought into the proper implementation of the patient outcome survey. More on this in the near future – here’s a video presentation of the initial results if you’ve not already seen it.

Marti, I’ll take a stab at replying (though maybe not answering) your questions:

• They’re only dealing with 35 patients – from Korea – from the pool of thousands of patients world-wide.

There were 170 patients in the study mentioned above, right? Only 28 in the ProDisc group?

• How are they installing ADRs in this Korean hospital that’s different from other surgeons worldwide that may be causing this problem with the ProDisc-C and Mobi-C?

This is an excellent question. As you know, techniques can vary (wildly?) across geographies. E.g., some docs use bone wax after inserting the ADR, which is said to prevent further overgrowth of the bone (HO). Does it help? Could it cause other problems? The answer seems to be “yes” and “yes.”

• Given the years and years the products have been on the market, why hasn’t this issue – at the cited rate of HO – surfaced before now?

HO has been raised as an issue, especially by me! My posts on this go back many years, just do a search. I’ve brought up the NSAID issue (for managing cervical post-op ADR inflammation) at least 20 times too. See the Bryan study above (posted in 2006) that mentions HO but not with the alarming numbers this multi-design ADR study does.

• Why aren’t surgeons with experience with multiple ADR designs substantiating the claims?

Another good question indeed. Do you think any of them want to get into this quagmire? Maybe I’ll ask Dr. Blumenthal, I believe he is the most experienced in terms of the diversity of devices that he and colleagues have implanted in the US.

• What correlation is there with the keel design (compared to the M6-C, which are more numerous but much smaller) and the problems the Koreas are having with HO?

I don’t think that this can be accurately inferred from the limited design of the study, though I am not a clinical evaluator by any measure. I keep coming back to my point: it’s the damage to the bone during the surgical process that creates the highest risk to “set up” the possibility of heterotopic ossification. Jeff & Nornie got into this discussion elsewhere, here’s an excerpt:

“…I have seen a video in which a well known European surgeon is rejoicing in the new technique that he has developed to implant the ProDisc-L. He says, "We just hammer(s) it into the bone". The video shows him coming from shoulder height with what looks to be a three pound rubber mallet. I'd eyeball that he delivered about 35 ft/lbs of momentum to whatever tool he'd placed over the ProDisc. If I ever need a ProDisc-L, I'm NOT going to see this particular surgeon…”

For patients with keeled cervical devices, you might consider this information:

- Work closely with your doctor(s) in the post-operative process. Study the imaging results carefully, especially for the first few years. Get your imaging studies and read the reports. Ask questions – especially about the proper meds/supplements to quell inflammation post-operatively. There’s variability in the answers you’ll get from spine doctors, so BE CAREFUL.

- Obtain a referral for a nutritionist and/or a naturopathic doctor. Learn about eating a balanced diet AND the many natural foods you can eat that are anti-inflammatory and detoxifying.

- In terms of HO, it appears that the outcome results are “all over the map” for cervical ADR patients. That said, this issue with cervical HO has not come up often within this community, but that’s an imprecise assessment. Again, I’ll fall back on the future survey results.

I hope this long post helps in some way. Peace and good health to us all.

[Marti in Benicia]

Hello, all. I linked my very experienced ADR surgeon, Nick Boeree, into our conversation about HO. In reading his feedback, I think it's a voice of sanity. Also, he points to factors that seem to increase the rate of HO ... including ethnicity. Read on:
_______________

Hi Marti,

Thanks for the link – I read it with great interest. I’m a little wary of making too many dogmatic statements since I think, like so many things, this is quite a complex issue and conclusions drawn from looking at too simplistically can be very misleading.

The sort of variable that need to be considered:

1. The patient! Heterotopic ossification occurs in a wide range of situations and can be a problem for hip surgery, upper limb joint replacements etc, and we know from that experience that some patients are just much more prone to it than others. Even this is likely to be due to multiple factors – genetic, biochemical, age, sex, hormonal – the list goes on. Race may well be a factor. It certainly seems that Korean patients may be vulnerable!

2. The pre-surgical stage of degenerative disease. I think this is a very important factor. It begs an important question – is HO a primary or a secondary phenomenon? In other words does it cause a stiffening in the motion of the operated level, or does it maybe occur as a secondary response to very limited movement following surgery. Certainly, in more advanced degenerative disease the motion segment will have become stiffer – secondary facet joint arthropathy is more advanced, soft tissue structures such as ligaments have shortened and stiffened etc. As you may know I have had discussions with several patients who have been told elsewhere that they can have 3 or 4 level ADRs including at very degenerative levels where I think ADR may be really a triumph of technology or surgical prowess over common sence! Sure, we can get an artificial disc in there, and the pushy surgeon will argue that it is all about technique and getting the disc mobile, but the reality is that the secondary changes may well be such that the disc hardly moves. And in that situation adjacent structures are likely to calcify or ossify. Equally, as a surgeon you need to do so much work on these very advanced levels, removing big circumferential osteophyte and excising unco-vertebral joints as well as widely clearing the lateral annulus, that you are really creating an ideal situation for HO to occur. Similarly, these discs are very narrow. Sure, they can be distracted out but the motion segment then is often really tight and very optimistic to think that it will really move much (or at all!). In these situations I often suggest a hybrid approach (sometime making the final call at surgery), for example fusing a very degenerate C6/7 but using ADR at C5/6. It may not be exactly what the patient wants to hear but I think it is always best to tell it how it is (at least as I see it!).

3. Surgical technique. ADR is very different to ACDF (anterior cervical discectomy and fusion) but for some surgeon, who may have simply progressed from inserting a cage to inserting a disc prosthesis, similar end plate preparation may be used. My personal view is to almost never use a burr. I clear away the end-plate cartilage but leave the bony endplate intact. I like small keels although I am yet to be convinced that this is an important fact in HO. I use bone wax but again, the reality is that this can only be applied over easily accessible areas, such as after anterior osteophyte removal. Another factor may be the degree of mobilization and retraction of the anterior para-spinal muscles. HO often seems to occur in muscles (e.g. around the hip) so respect for these muscles, avoiding overly aggressive mobilization and retraction may be important.

4. Post Op Management. NSAIDs are said to help although I am not aware of any trial that shows this and certainly we have to be careful about how long these are continued for. Post-op physiotherapy may also help, and certainly I think it is best for patients to have instruction in exercises to continue with in the long term. Keep it moving!

5. Prosthesis Design. If this is a factor we need to ask why. It’s easy to suggest it is the keel, but I suspect it may be more to do with the range of movement and particularly the nature of the movement created.

So, some of my views! Of course, when you appreciate the potential complexity of the situation it starts to become apparent why a properly useful study is actually very difficult to set up. To do so we need to focus on just one of the variables, eliminating the others or keeping them constant. Then you have to collect sufficient numbers in that small sub-group to make statistical analysis meaningful. There are statistical power calculations you can do to work out the numbers of patient you need depending on the likely difference in the two groups. Believe me, it is daunting and often virtually impossible to achieve in any reasonable time scale except with a multi-centre study. But first you guys over there need to get your FDA to let you do the surgery!

I’m sure to think of more things as soon as I finish but if so I’ll let you know. If you want to post these comments please feel free. I shall watch the debate with interest!

Very best wishes from your friend and surgeon!

Nick

[DAnn]

Hello, and thank you for this very useful information.

My question would be how should one recover from a hybrid surgery given this information? Is it better to move the neck (to reduce the bone growth) or keep it stable (as after fusion).

NSAIDs, if they help reduce the bone growth, are not generally used after fusion, right?

It seems the two procedures are contradictory in the recovery process. I'm just wondering as I'm considering very seriously a hybrid cervical procedure.

Thanks
DAnn

[Abbe]

I have been reading this thread with great interest. I am facing the decision about having a hybrid surgery at C5-C6 & C6-C7. One of the considerations that my doctor brought up was the use of keeled ADR might not be the best choice and he would like to use the (older?) Prestige ADR because it is affixed from the front with screws. I have looked at the two designs and I am very unsure of the advantages and disadvantages. This discussion of bone over growth was not brought up by my surgeon but a discussion about the risk of weakening the vertebrae was with the keel in the small cervical area. He said he would not do adjacent double disk replacement with a keeled designs because of the risk in weakening the bone and the possibility of injury in the future of something like a car accident where the neck would be involved. He made it sound like the vertebrae could be split in half. Very scary sounding to me... He said that he liked the front plate design better. So, does anyone have information about the older style Prestige which is also stainless steel. Here is a link to their study.

Artificial cervical disc replacement clinical trials - prestigedisc.com
Looking for input to help make an informed decision!

[CP7959]

I have the "Older" Prestige ST and have no problems. I also have a Spinal Kintetics M6 which has smaller keels. The M6 has fused over, the Prestige has not.

Just me situation, I'm sure they are many with different outcomes.

[biakenny]

IS this a problem for Lumbar as well? Are people complaining of pain after the disc fuse over the implant?