Laboratory is no substitute for a living human joint.

 

                  HOME |  HISTORY OF TOTAL JOINTS

---

 

One old engineer rule says:  When you try to improve a good construction it will usually break. The history how DePuy's improvements of the Charnley’s total hip model ended in fiasco vindicates this rule.

Most importantly, however, this fiasco demonstrates nicely another old rule: laboratory experiments cannot predict how well the new materials for artificial joints would behave in the human body.

The Sir John Charnley’s total hip model has been a highly successful device; some surgeons still are still speaking about it as “the gold standard”. It has been, however, produced by a relatively small local English manufacturer, Thackray’s. Sir John also took care personally of all development of “his” total hip device.  After Sir John’s death further development of his total hip model thus ceased and eventually the Thackray’s Company (named Cintor in the USA) was bought by DePuy Company, a worldwide manufacturer of orthopaedic devices.

After overtaking Thackray’s company, the engineers at DePuy decided to exploit the attraction of the Charnley^R Hip System’s name and produce an “improved version” of it. The improvement should be done on two fronts.

First, the engineers would use the new materials which were developed in the 1980’s for the bearing surfaces of the new total hip. These new bearing surfaces would produce much less wear particles; at least this was deduced from the laboratory tests of the new materials. Less wear particles means less osteolysis (bone dissolving disease) and lesser risk of osteolysis would thus make the new total hip more long-lived.

Second, the engineers would slightly change the outer shape of the femoral component so that it would be more stable in the cemented bed, at least according to the theoretical considerations (the new total hip would still use bone cement for fixation). More stable total hip means a more long-lived total hip. There were thus all theoretical reasons to suppose that the new, improved total hip would be much better than the Charnley’s original model. The term “theoretical” is important as we will see later. For patent reasons the new DePuy’s total hip device was named  Elite PlusTM total hip. It was introduced on the market in 1993; to the outer look it was practically undistinguishable from the original CharnleyR Hip System.

Picture: Upper device: The Charnley total hip underneath the Elite Plus total hip with Zirconia head (yellow)

Improvements implemented on the Elite Plus total hip proved to be a disaster. Here follows a short history how it was discovered and who paid for the miscalculation.

---

 

 New materials that went wrong:

The Elite Plus^R total hip offered the surgeons the choice of two materials: either the old classic materials used in Charnley’s total hip (polyethylene against stainless steel) or these excellent new materials (Zirconia made ceramic ball against new polyethylene Hylamer).

The conservative surgeons who wished could continue with the classic – they could use the John Charnley’s  total hip, slightly modified in the form, of course, but fabricated from the material that Sir John would approve.

 The surgeons who believed that new materials for bearing surfaces were really better could choose the following materials:

 

DePuy also offered a cup component made from a new polyethylene Hylamer^TM .  

The first laboratory tests done under simple conditions really supported such statement. But these test were done under very primitive conditions.

How was the wear of polyethylene measured in the laboratory?

The commonly used test to measure the wear of polyethylene was the so called Pin on the Disc test.

The advertisement maintained that the Elite Plus total hip with the new Zirconia ball articulating against the new Duraloc cup was the best choice guaranteeing the longest service life of this total hip model.

Was this claim right? Nobody could say, although lready in 1991, two years before the Elite Plus total hip with Hylamer cup was put on the market, there were scientists who warned that Hylamer was stiffer and less yielding than the conventional UHMWPE (ultra high molecular weight polyethylene). The scientists feared that the increased stiffness would increase and not reduce the wear if the Hylamer would be used in artificial hips and knees.

In 1993 when the Elite Plus was put on the market nobody could challenge the claim. To examine whether this claim was right would need a widespread clinical experiment conducted on many patients. According to the preliminary statistical calculations totally 200 operations on equally many patients would be needed for this test to compare the efficacy of the different material combinations used for bearing surfaces of Elite Plus models. These patients should be then followed for at least five years after the surgery, their total hips would be x-ray examined at regular intervals and wear of the bearing surfaces in their Elite Plus total hips measured and compared regularly.

This was a big experiment with many ethical question involved. But there was no other way to know whether DePuy’s statements were right. No private institution could afford to conduct such a widespread experiment on living human patients.

 It lasted three years after the introduction of the Elite Plus total hip on the market before the Swedish surgeons set out to perform this experiment. The ethical committee of the Lund University (Sweden) approved of this investigation -experiment on patients.

 It was planned that four randomly selected groups of patients, every group consisting of 50 patients, would be operated on with four different models of the Elite Plus prosthesis (Schewelov 2005) to get statistically significant results. Every patient group would receive an Elite Plus total hip device with one of the four available combinations of bearing surfaces as shown in  Fig 3.

Between 1994 and 1998, 120 patients were operated on randomly according to this plan. Then this human experiment was ended prematurely before all 200 patients could be operated on.  The reasons for the abrupt stop were the first clinical reports about the bad performance of the Hylamer. These reports demonstrated that Hylamer, contrary to the DePuy’s original claims,  wears off much more then the conventional HMWPE.

 The authors of one such paper wrote “We concluded that the wear characteristics of a Hylamer liner in vivo are inferior to those of a conventional ultra-high molecular weight polyethylene liner…. A patient who has a total hip replacement that includes a Hylamer liner should be monitored frequently for signs of wear and osteolytic changes.” (Livingston 1997)

Seven years after the abrupt stop of their clinical experiment, the Swedish surgeons evaluated the results of their experiment and in December 2005 published their results (Schewelov 2005).

 This report demonstrated that the Elite Plus models with the Enduron / Hylamer cup component produced 20% of failures during the seven postoperative years; this is about three times more failures than the internationally accepted benchmark (maximally 1% annually or 7% in seven years).

Radiological measurements demonstrated that Zirconia femoral head articulating with a Hylamer cup produced annually four times more wear particles than the “old” bearing combination of metallic head articulating against Hylamer cup.

The report demonstrated that Hylamer polyethylene is not “orthopaedic bearing material with superior quality for your patients”. It is a dangerous material, wearing too much and causing catastrophic rates of failures of total hip models where it was used. The material was silently retracted from the market and “one has issued the recommendation to follow up patients whose total hips contain this material”.

The report also demonstrated that  Zirconia^R  ceramic for femoral heads is not “the toughest, smoothest orthopaedic ceramic ”. Zirconia wears too much because Zirconium ceramic, from which Zirconia balls are made, is chemically unstable material that changes its characteristics with time. These small Zirconia balls were also recently retracted from the market.

With both “new” materials in DePuys Elite Plus total hip removed from the marked only the patients who still have these materials inside their bodies stayed. Now, you may ask whether it was ethical to start this study at all. Was the ethical committee right when it approved of this human experiment?

Professor Laurent Sedel, chairman for the Orthopaedic Department of the University of Paris (Paris, France), a surgeon renowned for his great knowledge of ceramic hips says that “this article is great” because it demonstrates that laboratory experiments on total hip devices cannot be used for prediction how the new total hip device would function in the patient’s body. There was no other way to prove that DePuy’s “new materials” were in reality change for the worse.

Professor Sedel also explains that the failure to predict behavior of new materials from laboratory tests is due to the fact that the testing machines, hip simulators, do not work in the environment that would be at least remotely like the conditions in the human body.

Moreover all these tests have been performed under the direction of the manufacturer, not on the independent laboratories of medical schools. The manufacturer is not interested in publication of “negative” (bad results) of laboratory tests.

Professor Sedel thus recommends that in the future, especially for European countries, no new materials for new types of total joints might be introduced without testing in independent (academic) laboratories.

The current trend is, however, the opposite: American orthopaedic surgeons are anxious that more and more orthopaedic research and education leaves the universities and goes to the manufacturer financed projects. And the situation is not better in the European countries. 

---

 Small changes in the form of the new hip device that went wrong

The use of new materials was not the only change that the DePuy’s engineers afflicted on of the well proven Charnley^R Hip System. The engineers also get the “logical idea” that small change of the Cobra-like form of the Charnley’s  shaft component would make of the Elite Plus total hip more stable.

The idea behind this was, of course, Sir John Charnley’s. The shaft component of his total hip was placed during operation in the still soft cement dough contained in the marrow hole of the thigh. The soft cement dough escaped and retreated as the tapered stem component ploughed through the dough. Sir John get the idea that placing a Cobra like flange on the upper part of the shaft component would compress the cement cylinder back into the marrow hole and make the shaft component more stable there. This was how the Cobra model of Charnley^R Hip System was conceived.

The engineers at DePuy thought that yet bigger flange and more cylinder like form of the shaft component would make it yet more stable within its cement bed.

 

Between 1994 and 1997,  the English surgeons at the Nuffield Orthopaedic Centre in Oxford operated on 118 patients with the Elite Plus total hip with the purpose to establish whether the new form of the Elite Plus shaft component really make the component more stable. Therefore the first operated on patients were followed closely for 2 years with  a very sensitive method of x-ray examination, so called RSA examination (Roentgen Stereophotogrammetric Analysis). This examination will reveal even small degrees of movement of the total hip device early on after implantation. Moreover, in contrast to usual x-ray studies that can demonstrate only when the component sinks down in the cement mantle, the RSA method will also demonstrate if the shaft component rotates in its cement mantle.

And that was what really happened.  The shaft component of the The Elite Plus total hip really did not sink downwards in its cement envelope, there the engineers succeeded magnificently. Instead, however, it rotated backwards.

In their recently published paper (Hauptfleish 2006) the British surgeons showed that the new Elite Plus total hip was not stable. Indeed, it was very instable, although it moved round its axis.  Because the shaft was more round than that of the Charnley’s model and the new instruments for insertion of the Elite Plus total hip produced a round hole in the thigh bone for the device, the femoral component began to rotate in the marrow hole soon after the surgery. This rotation movement could not be clearly seen on the ordinary x-ray pictures, but it was discovered easily with the RSA method.

Ten years after the surgery, 17% of all Elite Plus total hips already failed and needed revision operation, whereas x-ray controls discovered that further 41% of Elite Plus total hips were loose with revision operation looming.

The English surgeons concluded: “Our study has shown that the Charnley Elite-Plus femoral component has an unacceptably high rate of failure. It confirms that early evaluation of new components is important and that roentgen stereophotogrammetric method is a good tool for this. Our findings have also shown that rapid posterior head migration is predictive of premature loosening and a better predictor than subsidence.”

In “improving” the Charnley’s total hip model the engineers at DePuy followed blindly the John Charnley’s idea that the less the total hip sinks in its bed during the postoperative years the more successful the eventual result. The engineers made the Elite Plus total hip model really “un-sinkable”. Unfortunately, they did not recognize that total hip device that rotates in the cement bed is loose and will fails. They did not bother, probably, to do their own biomechanical studies before the production of the Elite Plus model.

We do not know how many Elite Plus total hip were operated on and eventually failed, these have been the "unlucky human experiments". Why those unlucky human experiments still do happen?

The idea that spawned the Elite Plus total hip is a good example of “armchair logic”. The surgeon and the engineer have a new idea how to produce a yet better total joint. Usually the idea is flawed in some way, but the surgeon lacks sufficient knowledge of mechanical facts and the engineer lacks sufficient knowledge of biological facts to discover the flaw. At first sight the logic of the new idea thus seems unassailable to both of them. Only the careful testing in laboratory might reveal the flaw – unfortunately, the tests in laboratory are often unrealistic and the flew is revealed too late, when the flawed device was  already used on patients.

There are many examples of this wrong “armchair logic” in the history of total hip joints (Teflon tragedy, surface replacement catastrophes in 1970’s, Christiansen catastrophe, to name some). The catastrophic failures of Elite Plus total hips are only one further example in the long row of the old tragedies.

Professor Sedel and the Swedish and English surgeons who published these two papers are right: Laboratory experiments are no substitute for a clinical study on living patients. Moreover, the laboratory examinations must be done in independent laboratories, not influenced by the manufacturer. Only then can these new total joint models be used for operation on small numbers of well informed patients. These patients must be followed up carefully on large centers equipped with modern x-ray laboratories for measurements of the device's stability. Only when careful follow up with repeated x-ray examinations demonstrated that  the new device really performs well can it be released on the market.

__________________________

References:

J. Hauptfleisch,  et al.:  The premature failure of the Charnley Elite-Plus stem, A CONFIRMATION OF RSA PREDICTIONS. Journal of Bone and Joint Surgery - British Volume, 2006; Vol 88-B:  179-183

Livingston BJ et al.: Complications of total hip arthroplasty associated with the use of an acetabular component with a Hylamer liner. J Bone Joint Surg /Am/ 1997; 79-A: 1529 - 38

vonSchewelov T.: Total hip replacement with zirconium oxide ceramic femoral head. J Bone Joint Surg-Br 2005; 87-B: 1631 - 35