week in review 4 - Orthopedics This...

VOLUME 7, ISSUE 22 | JULY 12, 2011

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picture of success

week in review

breaking news

4The Spine Blogger Un-masked? ◆ In February 2009 an anonymous blogger by the

name of Musculoskeletal Man began scorching surgeons for being greedy and spine companies for producing “me too” products. We’ve been asked if we know his identity. We just might.

9 InFuse , Part I◆ First The Spine Journal devotes its entire June 29 issue to repudiating studies—one

of which once appeared in its own pag-es. Then a Wall Street analyst speculat-ed that Medtronic might divest itself of InFuse or Spine or both. Surgeons are upset. It’s a mess. Using PearlDiver data we try to sort fact from fiction.

27 Dr. Ted Miclau, Part II ◆ Dr. Ted Miclau, the next president of the ORS, is al-

tering the future of orthopedics here and abroad. He is holding courses in Latin America that teach orthopedists how to design different clinical research methodologies and protocols.

18 Joint Replacements Recy-cled?........................................

Stem Cell Study for Degenerative Disc Disease..........................................................Medtronic Acquires Surgical Businesses..........................................................Deep Vein Thrombosis Drug Approved..........................................................OMNIlife Makes Bold Knee Replace-ment Claim..........................................................Bipartisan Appeals Court Upholds Insurance Mandate..........................................................Milliman Strikes at Lumbar Fusion in Florida

For all news that is ortho, read on.Part II

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Orthopedic Power RankingsRobin Young’s Entirely Subjective Ordering of Public Orthopedic Companies

Rank Last Company TTM Op 30-Day Comment Week Margin Price Change

This Week: Just when we thought it could not get worse for Spine, The Spine Journal launches a full tilt assault on InFuse, Medtronic and the authors of the original InFuse studies. Large joint recon, extremities and trauma dominate the Power Rankings this week. OFIX remains #1 with ZMH leaping 4 spots to #2.

1 1 Orthofix 14.72% 6.04%Up 42.75% in the last six months. Cash flows strong and rising. The single most diversified

orthopedic company for its size.

2 6 Zimmer 27.75 1.72Back to basics, baby. Large joints and high margins.

Has beat Wall Street’s expectations for a couple quarters now.

3 3 Kensey Nash 34.24 6.23Used to be a sleepy company. But two purchases, 34% operating margin means rising visibility on

Wall Street.

4 7 Stryker 25.23 2.88SYK’s diversification plus market leadership

delivers 19% return on equity and 17% return on total capital. Up 3 spots.

5 9Smith & Nephew

22.80 2.29Keeping with the return to large joints, extremities then add in wound care and SNN also moves up.

6 NR ConMed 9.54 7.35Power tools in surgery is about as basic as it gets. With CNMD, you also get the 3rd most attractive

price to sales ratio.

7 4 Exactech 8.08 2.88Recently added the Proliant polyaxial pedicle screw

system. Adding to Spine Biz.

8 2Johnson &

Johnson26.33 2.16

The Synthes deal took another step forward last week, but we’re still 10-11 months away from closing.

9 10Wright Medical

8.76 1.45It’s been a long strange trip for WMGI from the

days of breast implants to now. Maybe it’s time for a new owner.

10 5 NuVasive 6.84 5.10Reverberations from The Spine Journal’s attack on

InFuse are coloring all spine companies, even NUVA.



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Robin Young’s Orthopedic Universe

Company Symbol Price Mkt Cap 30-Day Chg Company Symbol Price Mkt Cap 30-Day Chg

Company Symbol Price Mkt Cap P/E Company Symbol Price Mkt Cap P/E

Company Symbol Price Mkt Cap PEG Company Symbol Price Mkt Cap PEG

Top Performers Last 30 Days

Lowest Price / Earnings Ratio (TTM)

Lowest P/E to Growth Ratio (Earnings Estimates)

Worst Performers Last 30 Days

Highest Price / Earnings Ratio (TTM)

Highest P/E to Growth Ratio (Earnings Estimates)

Company Symbol Price Mkt Cap PSR Company Symbol Price Mkt Cap PSR

Lowest Price to Sales Ratio (TTM) Highest Price to Sales Ratio (TTM)

1 MAKO Surgical MAKO $32.75 $1,341 11.39%2 Alphatec Holdings ATEC $3.74 $333 10.98%3 TranS1 TSON $4.83 $101 10.02%4 ConMed CNMD $28.79 $815 7.35%5 RTI Biologics Inc RTIX $3.07 $169 7.34%6 CryoLife CRY $5.83 $163 6.58%7 Kensey Nash KNSY $25.56 $218 6.23%8 Tornier N.V. TRNX $28.90 $1,128 6.09%9 Orthofix OFIX $43.18 $788 6.04%

10 NuVasive NUVA $34.01 $1,349 5.10%

1 Bacterin Intl Holdings BONE $2.60 $99 -27.78%2 TiGenix TIG.BR $1.26 $114 -11.40%3 Medtronic MDT $38.00 $40,317 -1.48%4 Integra LifeSciences IART $47.38 $1,353 0.59%5 Synthes SYST.VX $177.18 $21,045 0.69%6 Wright Medical WMGI $15.36 $599 1.45%7 Orthovita VITA $3.89 $300 1.57%8 Zimmer Holdings ZMH $64.52 $12,385 1.72%9 Johnson & Johnson JNJ $67.57 $185,219 2.16%

10 Smith & Nephew SNN $55.30 $9,871 2.29%

1 Medtronic MDT $38.00 $40,317 11.592 Johnson & Johnson JNJ $67.57 $185,219 14.023 Zimmer Holdings ZMH $64.52 $12,385 14.244 Kensey Nash KNSY $25.56 $218 14.525 CryoLife CRY $5.83 $163 15.76

1 NuVasive NUVA $34.01 $1,349 40.492 ArthroCare ARTC $34.15 $933 28.703 Wright Medical WMGI $15.36 $599 23.634 Synthes SYST.VX $177.18 $21,045 23.165 ConMed CNMD $28.79 $815 21.98

1 Orthofix OFIX $43.18 $788 0.972 Kensey Nash KNSY $25.56 $218 1.083 Exactech EXAC $18.55 $243 1.134 NuVasive NUVA $34.01 $1,349 1.185 Symmetry Medical SMA $9.48 $345 1.31

1 Alphatec Holdings ATEC $3.74 $333 3.022 Johnson & Johnson JNJ $67.57 185,219 2.913 CryoLife CRY $5.83 $163 2.864 ConMed CNMD $28.79 $815 2.485 ArthroCare ARTC $34.15 $933 1.77

1 Symmetry Medical SMA $9.48 $345 0.962 RTI Biologics Inc RTIX $3.07 $169 1.023 ConMed CNMD $28.79 $815 1.144 Wright Medical WMGI $15.36 $599 1.155 Exactech EXAC $18.55 $243 1.27

1 TiGenix TIG.BR $1.26 $114 184.172 MAKO Surgical MAKO $32.75 $1,341 30.283 Synthes SYST.VX $177.18 $21,045 5.714 Bacterin Intl Holdings BONE $2.60 $99 5.305 Tornier N.V. TRNX $28.90 $1,128 4.96

PSR: Aggregate current market capitalization divided by aggregate sales and the calculation excluded the companies for which sales figures are not available.

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VOLUME 7, ISSUE 22 | JULY 12, 20115The Spine Blogger Unmasked?By Walter Eisner

On Saturday, February 7, 2009, a new blog, published by the anon-

ymous Spine Blogger (TSB), appeared on the Internet (www.spineblogger.blogspot.com).

The blogger, who calls himself Mus-culoskeletal Man, was first brought to this writer’s attention by a former col-league at Orthopedics This Week. TSB promised to provide “a platform where the exchange of ideas, news, job oppor-tunities and the truth can be discussed in an open forum without Big Brother standing over us and threatening our livelihoods.” He requested that his fol-lowers use the platform without mali-cious name calling or vulgarities. “Strap yourself in, and enjoy the ride,” wrote the blogger.

And quite a ride it’s been as he and his followers quickly ignored the request.

Postings, Comments and Followers

Since inception, TSB has logged over 500 postings, listed 281 followers, and claimed 50,000 hits and 8,200 return-ing readers per month by the end of the first year. While reader comments were sparse at the beginning, TSB now regularly garners between 50 and 100 anonymous comments to his postings.

TSB’s postings and his follower’s com-ments, are generally informative and provide insight into the frustrations of anonymous spine sales reps. But over the years, as TSB dove into the chang-ing world of spine sales and threats

to spine reps’ livelihoods from PODs (physician-owned distributors), chang-ing distribution models and commis-sion cuts, many of the comments got ugly and personal.

We won’t list the names of the indi-viduals and companies scorched in the postings and comments. No need to repeat what may be false and damaging attacks.

“Me Too” Companies, Greedy Sur-geons and Besieged Sales Reps

Successful companies are frequently accused by TSB and followers of paying greedy surgeons to use their “me too” products. Companies that have failed or gone out of business are ridiculed for

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being run into the ground by incompe-tent dinosaurs that lacked the creativity to make their start-ups successful.

TBS and his followers also took on a nasty tone towards their employers and incredibly, their customers—the sur-geons. One TSB follower wrote that it was important to be able remain anony-mous because if their employers knew

what they really thought, they would be fired and their customers would stop buying products from them.

The site frequently feels like a therapy session for people in fear of their live-lihoods, their careers and the loss of a golden age in spine sales. TSB gives a vocal group of followers a forum to express their frustrations.

Here’s a TSB posting from July 2009:

“Witness the carnage in our indus-try that has resulted in over 500 different pedicle screws, nearly 300 cervical plates and countless TLIF, PLIF, ALIF and Cervical PEEK devices. Have all of these products really made a difference in out-comes? …Or, have these products saturated an already existing com-modity market? As investors hold on to their hard earned capital there will be fewer opportunities for ‘me too’ products to succeed. How will this shift affect the earning capa-bilities of the salesperson? There will be a shift in the commission structure resulting in less earnings for the distributor or direct sales-person. I know that many of you do not like reading this, but if the com-pany’s bottom line suffers, so will your ability to sustain your earning capacity.

“…What happens when companies start believing that they could exist without sales people and start to model their distribution model by selling to the hospitals directly? If you don’t think that’s possible, it has already been piloted by vari-ous small companies and tabled by larger organizations.”

Who Is TSB?

We are frequently asked if we know the identity of TSB.

We’ve wondered ourselves and we’ve heard other people’s speculation. But then, this past June 18, an email came our way from, we believe, a former colleague of ours and, lo and behold, it came from the same email address that is located on TSB’s blog.

The Spine Blogger ‘About me’ page


VOLUME 7, ISSUE 22 | JULY 12, 20117TSB only says on his website that he has a background in orthopedics and spine. In his 500 plus postings he has volunteered more information about his background.

Our former colleague’s public LinkedIn information says that he is a former VP Sales and Marketing at Custom Spine, former head of business development for Choice Spine and former Senior Director of Marketing Cervical at Sur-gical Dynamics. And, of course, he worked for OTW for a while.

In his own words, he writes:

“Began my career at Synthes USA as an AO/ASIF Consultant. After a successful career in sales I was hired by Stryker/Osteonics as part of the management team at Stryker

Trauma. Responsible for the initial concept of the T2 Antegrade/Retro-grade Femoral and Tibial Nail. Seg-ued into Business Development and Marketing at Surgical Dynamics and Blackstone Medical launching numerous spinal deformity systems. Worked as a consultant raising capital and negotiating licensing agreements between educational institutions and early growth stage companies. Spent one and half years at Custom Spine as VP of Sales and Marketing. Currently employed at Choice Spine in Business Develop-ment.”

Intoxicated With Entrepreneurial Fever

Three days before the launch of TSB, our former colleague posted the fol-

lowing comments on www.xconomy.com in response to the demise of IST (Innovative Spine Technologies.)

“During Wall Street’s heyday spi-nal implant companies sprung up because there was excess capital. Industry professionals became intoxicated with ‘entrepreneurial fever’ a by product of the artificial disc deals. New companies immedi-ately aligned themselves with sur-geon champions to create leverage with potential investors. Many sur-geons even invested in some of these companies.

“…at best IST was a “me too” company competing in a zero-sum market…Before ’09 is over many of these companies will either disap-pear, align themselves with a com-pany that compliments the gaps in their respective portfolios or be sold in ‘fire sales’.”

That got us thinking that we’ve read this language on TSB.

For instance,

On November 8, 2009, TSB posted the following:

“Entrepreneurs have contributed to the success of spine, considering that without their interest some of the same technologies that we sell today would have never made it to the market. But, has this ‘mania’ led to the unethical behavior that exists in today’s industry? If surgeons become ‘salesmen’ or public rela-tions experts for a product that they have invested in, or are being paid by a company to use a product, is this good for medicine? Advertisement

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VOLUME 7, ISSUE 22 | JULY 12, 20118“The total disc boom created what many in our industry still call ‘Entre-preneurial Fever!’ The dynamics of the economy has changed people’s expectations. It’s interesting to sit around a dinner table and listen to surgeons criticize the TARP pro-gram and condemn Wall Street when their own behavior leaves much to be desired. Sometimes you feel like saying; ‘look at who is calling the kettle black!’”

There was another posting by our for-mer colleague that made its way into the public realm.

Bribery, Wall Street and DoJ

On December 19, 2005, he respond-ed to New York Times columnist Paul Krugman’s column, “Drugs, Devices and Doctors” with a published letter titled: “The Me-First Medical Industry.”

“I have over 20 years experience within the medical device industry and would love to share with you a first hand account of how companies obfuscate the truth between what constitutes a medical consultant and what is an outright bribe to have the surgeon’s or physician’s business...

“…Wall Street has ramped up and sunk its teeth into the pharmaceu-tical and device world creating a culture of mad-money. Sometimes there is no rhyme or reason to an idea, yet with marketing and clini-cal backing, a potential star is born: the product. As a prominent surgeon once told me about the artificial disc, ‘As long as the F.D.A. approves it, I will slap as many of them in and let the next guy worry about it after I’m retired. I have stock options and that’s all that matters...’ “

In June 2009, TSB wrote the following:

“As most of you know, in the old days (…we actu-ally sold for a living and the market wasn’t bought by companies)... Unfortu-nately, until the Depart-ment of Justice steps in and makes an example of those that abuse their privilege our industry we will continue to ‘shoot ‘em up’ and ‘duke it out.’ The only casualty will be the patient who doesn’t know whether they really need surgery or are they being used to line someone else’s pocket?”

In July 2009, TSB wrote:

“…there are a percentage of surgeons that no longer want to be surgeons, they want to be entrepreneurs... They want a piece of the action…They are no longer just doctors, they are now master marketeers, selling themselves to the highest bidder regardless whether they believe in the technology or not.”

Admittedly, we have picked out a very small sampling of TSB’s writings, but the themes remain the same—“me too” companies, greedy surgeons and besieged sales reps whose employers look at them as a commodity.

Unmasked?

By September 2010, some of TSB’s fol-lowers began to call for his unmask-ing. A series of comments speculated that TSB was John Nieradka, our for-mer colleague at OTW. Another reader

commented that TSB was Nieradka and that one company mentioned by TSB should pursue slander and defamation charges against him.

“John N.” responded to followers that he was flattered, but TSB wasn’t him.

Then, as mentioned earlier, we received a communication at the end of June from TSB’s posted email address. The name used by that email writer? “Joe” Nieradka.

This writer doesn’t know a “Joe” Nieradka, but TSB either inadvertently unmasked himself or someone pur-posely tried to get the hounds off his trail.

If TSB is John Nieradka, “Say it’s so Joe.” ◆

Writer’s Note: We emailed TSB a list of questions for this story. He said he’d respond. We did not receive the reply in time for this story, but will report his answers when we receive them.

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VOLUME 7, ISSUE 22 | JULY 12, 20119InFuse, Part IBy Robin Young

“People often look to great athletes for lessons about performance. And for a surgeon like me, athletes do indeed have lessons to teach—about the value of perseverance, of hard work and

practice, of precision. But success in medicine has dimensions that cannot be found on a playing field. For one, lives are on the line. Our decisions and omissions are therefore moral in nature. We also face daunting expectations. In medicine our task is to cope with illness and to enable every human being to lead a life as long and free of frailty as science will allow. The steps are often uncertain. The knowledge to be mastered is both vast and incomplete. Yet we are expected to act with swiftness and consistency. It’s not only the stakes but also the complexity of performance in medicine that makes it so interesting and, at the same time, so unsettling.”

--- Atul Gawande, Better, A Surgeon’s Notes on Performance

Last week, the fruits of about six months of effort were published in

the form of an entire issue of The Spine Journal, and it has shaken the spinal implant industry to its core. The Spine Journal is the scientific publishing arm of the North American Spine Society (NASS), the largest spine surgeon orga-nization in the world. NASS’ charter is to “foster the highest quality, evidence-based, and ethical spine care.”

In its June 2011 issue, The Spine Jour-nal reviewed and repudiated several studies, one of which received the 2002 Volvo Award for clinical studies, saying of the studies that they suffered from “serious potential design bias” and “unpublished adverse events and internal inconsistencies”. Indeed, the investigators led by Dr. Eugene Carra-gee but including Drs. Eric L. Hurwitz and Bradley K. Wiener, pegged actual risk of adverse events at 10 to 50 times the estimates originally reported in those stud-ies. All of the studies in question were reporting on the clinical experience of the recombinant bone morphogenic protein, BMP-2, marketed by Medtronic, Inc. under the brand name InFuse.

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VOLUME 7, ISSUE 22 | JULY 12, 201110The cumulative effect of The Spine Journal’s critical review of these 13 studies was to crystallize the mounting criticisms of InFuse and its past marketing by Medtronic. But Carragee et al. went further. Repeatedly in both the critical review and then in the accompanying editorial, Carra-gee and his colleagues repeatedly returned to the theme that the authors of the 13 studies had received millions of dollars of payments from InFuse’s supplier, Medtronic. While the authors did not word-for-word link such payments to the flaws in the studies, it is the opinion of this reader that that was the clear and obvious intent.

Spine surgeons, hospitals, NASS, and Medtronic itself are reeling from these accusations. The Spine Journal, for its part, appears to be engaged in an institutional mea culpa and is taking the lead in reviewing and correcting its own past.

To cap it all off, the editors (Carragee, Ghanayem, Weiner, Bono and Roth-man) chose a tabloid like phrase to include in their editorial with which to signal the importance of this issue—“Years of Living Dangerously”.

Decisions and Omissions

Between 2002 and 2004, 13 InFuse (rhBMP-2) studies were published in peer review journals including The Spine Journal. These studies, which are summarized in the table below, tested different doses of InFuse in 780 spine fusion patients.

The total number of adverse events reported by those clinical investigators was ZERO.

Over the ensuing years, new studies began to be reported from podiums and in the pages of spine journals describing InFuse complications in all manner of spine fusion surgeries.

In June 2008, the FDA issued a Public Health Notification of life threatening complications associated with rhBMP-2 use in cervical spine surgery:

‘‘These complications were associated with swelling of neck and throat tissue, which resulted in compression of the airway and/or neurological structures in the neck. Some reports describe difficulty swallowing, breathing or speak-ing. Severe dysphagia following cervical spine fusion using rhBMP products has also been reported in the literature. Most complications occurred between 2 and 14 days post-operatively with only a few events occurring prior to day 2. When airway complications occurred, medical intervention was frequently necessary. Treatments needed included respiratory support with intubation, anti-inflammatory medication, tracheotomy and most commonly second sur-geries to drain the surgical site [17].’’

Tellingly, one surgeon, Dr. David G. Malone of Oklahoma, who was part of the original FDA approved study of InFuse (rhBMP-2/PLIF trial) reported to the FDA at a public meeting in 2002 that, ‘‘two of the [InFuse] patients had significant posterior bony over-growth impinging on their nerve roots requiring additional surgery. One patient, who was my patient, required two surgeries to clear excessive bone growth from his spinal canal.’’

Dr. Malone continued: ‘‘BMP may lead to excessive bone growth and may cause significant neural impingement if placed in posterior lumbar interbody type of device.’’ The major adverse events in Dr. Malone’s patients resulting in reoperation were not included in the Haid et al. article which reported the results of that study.

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VOLUME 7, ISSUE 22 | JULY 12, 201111Here is the table of the thirteen studies reviewed by Eugene J. Carragee, M.D., et al.:

Using CONSORT recommendations for assessing study design and adverse event reporting, Carragee et al. concluded: “The estimates of rhBMP-2 safety from the original publications underestimated rhBMP-2–related adverse events of the product. In the small pilot studies, there was inadequate numbers [sic] to assess safety, but some suggestion of potential harms was seen in at least one study (Boden SD, Kang J, Sandhu H, Heller JG. Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies. Spine 2002;27:2662–73). In the larger trials, there is evidence in each trial that rhBMP-2 complications may be common and may be serious; but in each publication these were unreported.”

Carragee et al. noted that the authors of the Boden et al. study were consultants for InFuse and that one of the authors was also a Medtronic stockholder. Importantly, the Boden et al. article was also accompanied by a critical commentary by Neil Kahanovitz, M.D. that provided balance and questioned the study’s too-promising conclusions and the author’s objectivity.

He continued: “The subsequent reporting of additional studies, the review of administrative, government documents, and subsequent follow-up cohort data have given a fundamentally different picture of morbidity associated with rhBMP-2 use in

Source: The Spine Journal, June, 2011

Authors# of

Patients

ReportedAdverse Events

Author’s Comments Type of Spine Surgery

Boden et al. 11 0“There were no adverse events related to

rhBMP-2 treatment”Anterior interbody (LT-cage, lumbar, rhBMP-2)

Boden et al. 20 0“There were no adverse events directly

related to the rhBMP-2”Posterolateral (lumbar +/- instrumentation)

Burkus et al. 143 0“There were no unanticipated device-related

adverse events…”Anterior interbody (LT-cage, lumbar, INFUSE)

Burkus et al. 24 0“There were no unanticipated adverse

events related to the use of INFUSE Bone Graft”

Anterior interbody (bone dowel, lumbar, INFUSE)

Burkus et al. 79 0 None reported (2005)

Burkus et al. 277 0 None reported Anterior interbody (LT-cage, lumbar, INFUSE)

Baskin et al. 18 0“There were no device related adverse

events”Anterior interbody (cervical, INFUSE)

Haid et al. 34 0No unanticipated device-related adverse

events occurred”Posterior interbody fusion (lumbar INFUSE)

Boakye et al 24 0

Analysts of our results demonstrated the safety and efficacy of this combination of

cervical spine fusion therapy…a 100% fu-sion rate and nonsignificant morbidity”

Anterior interbody (cervical, INFUSE)

Dimar et al. 53 0 None reported Posterolateral (lumbar, INFUSE, and pedicle screws)

Glassman et al. 148 0 None reported Posterolateral (lumbar, AMPLIFY, and pedicle screws)

Dimar et al. 239 0“No adverse event that was specifically

attributed to the use of rhBMP-2 matrix in the study group was identified”

Posterolateral (lumbar, AMPLIFY, and pedicle screws)

Dawson et al. 25 0 None reported Posterolateral (lumbar, INFUSE, and pedicle screws)

Total 780 0 99% CI<0.5% adverse event rate


VOLUME 7, ISSUE 22 | JULY 12, 201112spinal surgery. In retrospect, several prominent spine researchers were openly skeptical about the validity of the original pub-lications. Inconsistencies in the data and study conclusions were raised by Smoljanovic et al. soon after the industry-spon-sored studies were published. Others questioned the perspective and objectivity of the published presentations”. Kahanovitz, commenting on the Haid et al. study, wrote, ‘‘Unfortunately, the authors of this study appear to have been overwhelmed by their enthusiasm of using recombinant human bone morphogenetic protein type 2 (rhBMP-2).’’

Shock and Anger

Medtronic’s Doug King, president of Medtronic Spinal, sent a letter to physicians on July 1, a week after The Spine Journal launched its full tilt blast at InFuse. In his letter, King said, “Needless to say, we were shocked and also puzzled about many of these allegations, especially the allegations that zero adverse events were reported, cumulatively, in these studies of rhBMP-2.”

King went on to assure Medtronic’s surgeon customers, hospitals and his own employees that “…it’s important to note that The Spine Journal articles do not question the integrity of the safety data reported by Medtronic to the FDA which led to the approval of InFuse Bone Graft. The “Information for Use” provided in the InFuse Bone Graft package provides clinicians with detailed product information, including adverse events, warnings and other relevant information.”

In other words, Medtronic reported all the data, adverse events included, to the FDA and then placed adverse event warnings in the package inserts which accompany every dose of InFuse Bone Graft.

Then King reminded his stake holders (and this must make the editors of the peer review journals who published the now infamous studies cringe): “The 2000-2009 publications criticized in this issue of The Spine Journal previously underwent detailed pre-publication peer review by top-tier journals, during which these extraordinary allegations of gross under-reporting of adverse events were not raised. We believe that a thorough examination of the issues in The Spine Journal articles is required.”

King finished his letter with the announcement that Medtronic is launching its own independent review of The Spine Journal articles and has commissioned an independent, formal systematic review of InFuse Bone Graft published literature.

The reaction from surgeons was more pointed, emotional if not downright angry. One wrote to OTW:

“The points made are to a certain extent valid. BUT a headline of “Years of Living Dangerously” is a little of over the top. We definitely need to scrutinize industry supported research as the tendency by industry is to bring pressure to bear, but as researchers we must own our own data and have the gumption to publish it. The FDA is not blameless in this debacle. This is a drug not a device approved without dosage or delivery system (LT Cage??). YET I DON’T THINK I CAN DO MIS WITHOUT IT. My fear is that we will now ‘throw the baby out with the bathwater,’ lose a valuable tool that was rushed to market by a powerful industry giant and a few guys that caved to them.”

The anger that we heard from surgeons was widespread although its expression moved around from, initially, the messenger (Carragee, The Spine Journal and NASS) then to Medtronic and finally to the FDA. But, above all, what we heard from our surgeon readers was that this retrospective study, the tabloid like comments “living dangerously” and the subsequent viral explosion of stories created yet another storm of attacks on the profession of spine surgery.

One Wall Street analyst speculated that Medtronic may pull InFuse from the market and may even consider divesting the entire spine business. Shivers ran throughout the spine surgeon community at the thought of losing InFuse.

What’s Reality?

Dr. Thomas Zdeblick, one of the surgeons criticized by Carragee for not reporting adverse events in his InFuse studies responded in a televised interview saying: “All of those other complications that you just mentioned, other than sterility, were

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VOLUME 7, ISSUE 22 | JULY 12, 201114in what’s called off-label use of InFuse, different operations than I use it in. I know that’s hard for people to understand, but in science, if something’s not statistically different, it’s the same.”

Commenting on the Carragee review in The Spine Journal, Dr. Zdeblick said: “As a crusader, I think [Carragee’s] on that path to get people to go back in time to less expensive days. I don’t want to go back there. I’d rather do what we do now because the results we get from spine surgery now are better than they’ve ever been.”

PearlDiver, OTW’s sister company which has approximately 1.9 billion patient records, has thousands of InFuse patient records as well. We asked PearlDiver senior analyst Scott Ellison to check the record for complications from the use of bone morphogenic protein and also to check complications from the use of bone graft harvesting in spine fusion studies.

We found that complications rates when BMP is used are slightly less than when bone graft harvesting is used. More impor-tantly, however, we found that complication rates with BMP have been declining—even though the number of surgeries using BMP has been rising.

Here’s the data and we’d like to invite an independent researcher to also study our data and see if our data is consistent with Carragee’s conclusions or whether reality is somewhere else.

The following table presents U.S. procedure volumes for insertion of bone morphogenic protein (ICD-9 code 84.52 and CPT code 22851) and the associated complication rates for patients under 65 and then for patients over 65. This data is processed by PearlDiver and was collected from the Medicare Standard Analytical File, the Medicare Carrier File and the National Inpatient Sample.

Source: PearlDiver Technologies, Inc./Scott Ellison, Senior Analyst

2005 2006 2007 2008 2009

U.S. volume of BMP spine cases 85,833 108,843 120,688 128,915 137,856

Volume under age 65 52,364 66,938 73,493 83,675 89,478

Volume age 65 or older 33,469 41,905 47,195 45,240 48,378

Total patient complications 11,701 13,983 14,993 13,414 11,284

All ages complication rate 13.6% 12.8% 12.4% 10.4% 8.2%

Under age 65 complications(distinct patients)

3,639 4,385 4,408 4,210 3,542

Under 65 complication rate 6.9% 6.6% 6.0% 5.0% 4.0%

Age 65 and older patient complica-tions (distinct patients)

8,063 9,598 10,585 9,204 7,742

65 and over complication rate 24.1% 22.9% 22.4% 20.3% 16.0%

Total patient refusions 5,227 5,766 6,372 5,772 5,928

All ages refusion rate 6.1% 5.3% 5.3% 4.5% 4.3%

Under age 65 refusions 1,580 1,595 2,027 1,878 1,929

Refusion rate 3.0% 2.4% 2.8% 2.2% 2.2%

Age 65 or older refusions 3,647 4,171 4,345 3,894 3,999

Refusion rate 10.9% 10.0% 9.2% 8.6% 8.3%


VOLUME 7, ISSUE 22 | JULY 12, 201115Then we asked PearlDiver (Scott Ellison) to do the same analysis for bone graft harvesting (ICD-9 code 77.59). Here’s that data.

What this data shows is that complication rates have declined consistently over the past five years. For this analysis, Ellison looked at a wide range of complications.

Did complications decline because spine surgeons were changing their use of InFuse based on both personal experience and clinical papers? Or was the decline due to other factors? Whatever the reasons, there is little question, we think, that spine surgeons have reduced the level of complications when using BMP and that the rate of complications from using BMP is less than complication rates when bone is excised from one part of the patient to place in another. The chart above shows this pattern.


2005 2006 2007 2008 2009

U.S. Volume of Excision of other bone for graft, except facial bones

103,431 90,761 97,945 156,398 170,571

Volume under age 65 74,714 64,468 68,779 110,828 120,871

Volume age 65 or older 28,717 26,293 29,166 45,570 49,700

Total patient complications 17,281 12,975 13,803 20,493 13,822

All ages complication rate 16.7% 14.3% 14.1% 13.1% 8.1%

Under age 65 complications (distinct patients)

10,374 6,856 7,808 10,935 7,155

Under 65 complication rate 13.9% 10.6% 11.4% 9.9% 5.9%

Age 65 and older patient complica-tions (distinct patients)

6,907 6,119 5,995 9,558 6,668

65 and over complication rate 24.1% 23.3% 20.6% 21.0% 13.4%



VOLUME 7, ISSUE 22 | JULY 12, 201116From our perspective, spine surgeons appear to have been walking up a learning curve and are selecting the patients more appropriately for InFuse and then they are implanting and dosing InFuse better and better. Furthermore, the increasing use of InFuse has allowed for more judicious bone graft harvesting and THOSE complication rates are declining as well.

Fair Warning

It’s hard to fathom how 13 studies of the use of InFuse in about 780 patients could fail to account for adverse events other than to conclude—especially after reading Carragee et al.’s repeated documentation of millions of dollars of payments by Medtronic to the study’s authors—that corporate funding was the proximate cause.

Still there was fair warning of InFuse’s adverse events in the years after these 13 studies. As the following table of clinical studies demonstrates, every spine surgeon who even glanced at a spine journal or swung by a society meeting learned about BMP’s adverse events.

Complications Associated with Bone Morphogenic Proteins – a partial list of the peer review articles since 2006

Article Title Year Journal Cited by Authors

Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine

fusion2006 SPINE 149 LBE Shields, GH Raque, SD Glassman

Complications of anterior cervical discectomy and fusion us-ing recombinant human bone morphogenetic protein-2

2007European Spine

Journal72 R Vaidya, J Carp, A Sethi, S Bartol, J Craig

Neurologic impairment from ectopic bone in the lumbar canal: a potential complication of off-label PLIF/TLIF use of

bone morphogenetic protein-2 (BMP-2)2008 The Spine Journal 70 DA Wong, A Kumar, S Jatana, G Ghiselli

Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy and fusion: a case study

2007 The Spine Journal 68 B Perri, M Cooper, C Lauryssen

Vertebral bone resorption after transforaminal lumbar inter-body fusion with bone morphogenetic protein (rhBMP-2

2006Journal of Spinal Dis-orders and Techniques

62 JW McClellan, DS Mulconrey

Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion

procedures2009 JAMA 53 KS Cahill, JH Chi, A Day

Vertebral osteolysis after posterior interbody lumbar fusion with recombinant human bone morphogenetic protein 2: a

report of five cases2007 The Spine Journal 48 KU Lewandrowski, C Nanson

Complications in the use of rhBMP-2 in PEEK cages for inter-body spinal fusions

2008Journal of Spinal Dis-orders and Techniques

43 R Vaidya, A Sethi, S Bartol

A comprehensive review of the safety profile of bone morpho-genetic protein in spine surgery

2008 Neurosurgery 40 D Benglis, MY Wang

The perioperative cost of Infuse bone graft in posterolateral lumbar spine fusion

2008 The Spine Journal 39 SD Glassman, LY Carreon, MJ Campbell

Complications associated with single-level transforaminal lumbar interbody fusion

2009 The Spine Journal 34 JA Rihn, R Patel, J Makda, J Hong, DG Anderson

The safety and efficacy of anterior cervical discectomy and fusion with polyetheretherketone spacer and recombinant

human bone morphogenetic protein–2: a review …2008

Journal of Neurosurgery

26 LM Tumialán, J Pan, GE Rodts Jr

A case of psoas ossification from the use of BMP-2 for pos-terolateral fusion at L4-L5

2008 SPINE 18 RS Brower

Adverse events in patients re-exposed to bone morphogenetic protein for spine surgery

2008 SPINE 18 LY Carreon, SD Glassman, DC Brock, JR Dimar

RhBMP-2 versus iliac crest bone graft for lumbar spine fusion in patients over 60 years of age: a cost-utility study

2009 SPINE 18 LY Carreon, SD Glassman, M Djurasovic

Heterotopic ossification after the use of commercially avail-able recombinant human bone morphogenetic proteins in

four patients.2008 The Journal of Bone 16 TW Axelrad, B Steen, DW Lowenberg



Finally, it is important to make note that as part of the critical review of InFuse, Carragee recused himself as editor-in-chief (EIC) of that issue of The Spine Journal to avoid any perceived conflicts of interest. Christopher Bono, M.D. took on the role of EIC and all of the articles, including Dr. Carragee’s were peer-reviewed by non-conflicted, national experts on BMP and analysis/statistics, evidence and methods.

Next Week: Corporate Funding of the Infuse Studies and Ramifications of The Spine Journal’s review to Innovation and Self-Regulation in Spine Surgery ◆

Histopathologic inflammatory response induced by recom-binant bone morphogenetic protein-2 causing radiculopa-

thy after transforaminal lumbar interbody fusion2010 The Spine Journal 5 RD Muchow, WK Hsu

Complications associated with the use of bone morphoge-netic protein in pediatric patients

2010Journal of Pediatric

Orthopedics4 ME OETGEN

… -mediated inflammatory reaction following posterior cervical decompression and fusion associated with recom-binant human bone morphogenetic protein-2: a case …

2010 S[OME 3 BN Robin, CD Chaput, S Zeitouni, MD Rahm

Use of Bone Morphogenetic Proteins in Spinal Fusion Surgery for Older Adults with Lumbar Stenosis: Trends,

Complications, Repeat Surgery, and Charges2011 SPINE 1

RA Deyo, A Ching, L Matsen, BI Martin, W Kreuter

Complications with recombinant human bone morpho-genetic protein-2 in posterolateral spine fusion associated

with a dural tear2010 The Spine Journal 1 SD Glassman, JL Gum, CH Crawford III…

Administration of Human Recombinant Bone Morphoge-netic Protein-2 for Spine Fusion May Be Associated With

Transient Postoperative Renal Insufficiency2010 SPINE 0 JM Latzman, L Kong, C Liu

Delayed Pleural Effusion After Anterior Thoracic Spinal Fusion Using Bone Morphogenetic Protein-2

2011 SPINE 0CK Kepler, RC Huang, D Meredith, M Cunning-

ham

Radiographic and CT Evaluation of Recombinant Human Bone Morphogenetic Protein-2-Assisted Spinal Interbody

Fusion2011

American Journal of Roentgenology

0 A Sethi, J Craig, S Bartol, W Chen

Use of recombinant human bone morphogenetic protein-2 as an adjunct for instrumented posterior arthrodesis in the

occipital cervical region: An analysis of …2010 Junction and Spine 0 DK Hamilton, JS Smith, DL Reames

Perioperative complications of recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge

versus iliac crest bone graft for posterior …2007

European Spine Journal

16 CH Crawford III, LY Carreon, MD McGinnis

Symptomatic ectopic bone formation after off-label use of recombinant human bone morphogenetic protein-2 in trans-

foraminal lumbar interbody fusion2010 SPINE 13 NF Chen, ZA Smith, E Stiner, S Armin

A cost analysis of treatment of tibial fracture nonunion by bone grafting or bone morphogenetic protein-7

2009International Ortho-

paedics13 Z Dahabreh, GM Calori, NK Kanakaris

Recombinant human bone morphogenetic protein-2-induced radiculitis in elective minimally invasive transforaminal lum-

bar interbody fusions: a series review2009 SPINE 12 SA Mindea, P Shih

Complications of recombinant human BMP-2 for treating complex tibial plateau fractures: a preliminary report

2009Clinical Orthopedics and Related Research

11 S Boraiah, O Paul, D Hawkes, M Wickham

Is it safe to use recombinant human bone morphogenetic protein in posterior cervical fusion?

2009 SPINE 8 GK Hiremath, MP Steinmetz

High-dose bone morphogenetic protein-induced ectopic abdomen bone growth

2010 The Spine Journal 6 H Deutsch

Formation of painful seroma and edema after the use of recombinant human bone morphogenetic protein-2 in pos-

terolateral lumbar spine fusions2010 Neurosurgery 6 MP Garrett, UK Kakarla, RW Porter

Promoting fusion in minimally invasive lumbar interbody stabilization with low-dose bone morphogenic protein-2--

but what is the cost?2010 The Spine Journal 5 RJ Mannion, AM Nowitzke

Source: Google Scholar



Medtronic Acquires Surgical Businesses

Medtronic, Inc. announced on July 7 that it was acquiring Salient Sur-

gical Technologies Inc., of Portsmouth, New Hampshire, and Peak Surgical Inc. of Palo Alto, California.

The two companies, in which Medtron-ic already holds an ownership stake, will join the company’s surgical tech-nologies business. Net of Medtronic’s existing ownership, the deals are worth $480 million for Salient and $105 mil-lion for Peak.

Salient Surgical Technologies

Salient is a leader in the advanced energy category for haemostatic sealing of soft tissue and bone in a variety of surgical procedures including ortho-pedic surgery, spine, open abdomi-

nal and thoracic procedures. Salient’s AQUAMANTYS system with patented TRANSCOLLATION technology will broaden Medtronic’s portfolio of surgi-cal products.

Salient’s technology has been used to care for more than 650,000 patients.

Peak Surgical

Peak is a leader in the emerging field of advanced energy surgical incision technology. The technology is based on its proprietary PlasmaBlade technology, which consists of a family of dispos-able cutting devices with proprietary insulation technology that offers, says the company, the exacting control of a scalpel and the bleeding control of tra-ditional electrosurgery with minimal thermal tissue damage.

Peak’s technology is cleared for use in a variety of settings, including ear, nose and throat (ENT), plastic reconstruc-tive, orthopedic and general surgical

applications. The PEAK Surgery Sys-tem was launched in July 2008 and has been used by U.S. surgeons on more than 25,000 patients.

According to the company statement, annualized revenue for Salient is approximately $100 million while Peak is at $20 million, and “growing rapidly.”

Medtronic’s surgical business reached $1 billion in sales for the first time last year.

—WE (July 8, 2011)

Bonovo Forms Bonovo Recon

Going deeper into China…Bonovo Orthopedics, Inc. is announcing

that it has formed Bonovo Recon, a new division dedicated to accelerating the

growth of the company’s hip and knee product development and sales initia-tives. This new division already has a full line of hip and knee products for sale to the China orthopedic market.

No newcomer to China, Bonovo entered the country’s joint reconstruction mar-ket in 2007 through the acquisition of Kangknow, Inc., a Tianjin-based hip company. The following year, Bonovo partnered with Japan Medical Materi-als, Inc. (JMM) to bring a full line of

company

Salient Surgical/Peak Surgical Technologies

Nat/Wikimedia Commons


VOLUME 7, ISSUE 22 | JULY 12, 201119imported hip and knee products to the Chinese market. Through the JMM partnership, Bonovo has introduced the first ceramic bi-surface knee sys-tem to China designed specifically for the Asian anatomy and lifestyle with improved knee flexion and durability. Bonovo’s newly formed reconstruction division has a full pipeline of cemented and uncemented hips and knees under-going clinical trials in China, as well as a product development and instrument design team located in Beijing.

According to Peter Slate, Bonovo’s chief executive officer, the company has developed one of the most comprehen-sive total joint design and development teams in China, along with a full pipe-line line of products. The formation of Bonovo Recon provides Bonovo with a more focused platform to continue making investments in this exciting market.

To go along with this growth, the com-pany has added key personnel to its joint marketing and R&D teams and has reorganized its sales group to form a fully dedicated hip and knee sales team. Additionally, it has increased its joint reconstruction training efforts through the Bonovo Academic Alliance, its organization dedicated to training and enhancing the connection between Eastern and Western surgeons.

In the June 26, 2011 news release, Chip Bao, Bonovo’s president of Asia, stated, “The formation of Bonovo Recon solidifies Bonovo’s commitment to pro-vide customers throughout China with a complete portfolio of hip and knee products and a fully dedicated team committed to training and personal ser-vice. Through Bonovo Recon, we will continue to play a leadership role in improving patient care in the Chinese orthopedic market.”

Peter Slate told OTW, “We have been developing our reconstruction strategy to address current market needs of the market and those going forward. Our key areas of investment have been in surgeon training and product devel-opment. The reconstruction market in China will be one of the fast growing revenue segments in Chinese orthope-dics. There will continue to be great demand for these products...both imported and domestic Chinese manu-factured. We are developing products that are competitive in both categories to be successful.”

—EH (July 1, 2011)

Bipartisan Appeals Court Upholds Insurance Mandate

The score is now 1-0 at the federal appeals court level in favor of the

law that will require Americans to pur-chase health insurance coverage.

A three judge panel for the U.S. Court of Appeals for the 6th Circuit in Cin-cinnati ruled 2-1 on June 29 that the minimum coverage provision “is a valid exercise of legislative power by Con-gress under the Commerce Clause.”

In addition to being the first appellate court to rule in favor of the mandate, it was also the first time a Republican-appointed judge sided with the govern-ment.

The Cincinnati decision was based on an appeal brought by the conserva-tive Thomas More Law Center, which argued that Congress overstepped its constitutional authority to regulate commerce in passing the mandate.

The three-judge panel disagreed. Jimmy Carter appointee Judge Boyce F. Martin Jr., wrote the mandate is constitutional because, “Congress had a rational basis to believe” that the provision would affect interstate commerce and that it was “essential” to the law’s broader goals of reforming the healthcare market.

There are still two decisions pending from other appeals courts. One at the 4th Circuit in Richmond, Virginia, and

legal

U.S. Court of Appeals; Source: uscourts.gov


VOLUME 7, ISSUE 22 | JULY 12, 201120biologicsone at the 11th Circuit in Atlanta, Geor-

gia. The Atlanta appeal by the govern-ment is waiting to decide on a Republi-can-appointed federal judge’s ruling in Florida that the entire law, not just the mandate, is unconstitutional.

More than 30 lawsuits have been filed since the Patient Protection and Afford-able Care Act was passed by Congress in March 2010, resulting in several rul-ings by lower court judges that, until now, have been decided along partisan lines. George W. Bush appointee Judge Jeffrey Sutton voted with the govern-ment in the Cincinnati decision.

The U.S. Supreme Court is expected to take one or more of the cases, per-haps as soon as its coming term, which starts in October. That means a poten-tial Supreme Court decision during an election year.

—WE (June 30, 2011)

Stem Cell Study for Degenerative Disc Disease

An Australian regenerative medicine company has received clearance

from the United State Food and Drug Administration to begin a Phase 2 clini-cal trial of its Mesenchymal Precursor Cell (MPC) product for the treatment of degenerative disc disease (DDD). The company, Mesoblast Limited, claims its repair therapeutic is a non-invasive treatment for the principal cause of chronic low back pain.

The multi-center Phase 2 trial in the United States and Australia will enroll 100 patients with chronic low back pain due to lumbar disc degeneration. In 60 of the patients, researchers will inject Mesoblast’s allogeneic or off-the-shelf disc regeneration MPC product into the dam-aged disc using one of two doses com-bined with hyaluronic acid carrier. They will then compare the treatments’ safety and efficacy at six months against 40 control patients who were injected with either hyaluronic acid or saline alone.

According to Mesoblast, the Phase 2 trial will build on preclinical results which showed that six months after a

single low-dose injection of the com-pany’s allogeneic MPCs into severely damaged intervertebral discs there was dramatic reversal of the degenerative process, regrowth of disc cartilage, and sustained normalization of disc pathol-ogy, anatomy and function.

Severely degenerated discs which served as preclincal result controls (either not injected or were injected with hyaluronic acid) continued to demonstrate significantly reduced disc height, disordered disc structure, dis-rupted histopathology, and reduced cartilage content compared with healthy non-degenerated discs over six months of follow-up.

Up to 15% of people in industrialized countries have chronic back pain last-ing more than six months. The com-pany Chief Executive, Professor Silviu Itescu, said Mesoblast had developed a novel therapeutic approach to reverse disc degeneration and address the number one cause of chronic low back pain. “There is a clear need for a prod-uct to reverse the degenerative pro-cess and regenerate the disc back to a healthy state. We believe our allogeneic adult stem cell product may represent a major breakthrough into this unmet market segment.”

—BY (July 6, 2011)

Advertisement Mesoblast Limited/Morguefile

http://www.ldrspine.com


VOLUME 7, ISSUE 22 | JULY 12, 201121Joint Replacements Recycled?

With American orthopedists installing more than a million

artificial hips and knees a year in mostly aging patients (according to The Ameri-can Academy of Orthopaedic Surgeons) has anyone thought about the ultimate fate of all those metal implants? One who has is Ray Saadeh, founder of Alternative Solutions USA, a California start up that collects used joint replace-ment parts.

They arrive at his warehouse in 10 gal-lon drums, shipped to him by crema-toriums around the country. Saadeh sandblasts the parts and sorts them out. He then ships them on to be recycled, melted down and eventually turned into other objects, possibly even new implants.

Saadeh is believed to be the only non-profit in the West that salvages orthope-dic body parts. In the past, such items would have been tossed in the trash or buried. Crematories have never been exactly sure what to do with recovered implants. “These metals have a useful

second life,” said Tom Snyder, a vice president with Stewart Enterprises of New Orleans, which owns 400 funeral homes, crematories and related busi-nesses. “Quite frankly, burying them is not very environmentally friendly and provides no benefits to anyone.”

Alternative Solutions collects the implants at no cost to the cremato-ries, providing the barrels and footing the shipping costs. It can take several months for a crematory to fill a drum. Saadeh sells the material to a Los Ange-les recycler and turns over about 60% of the money to the American Red Cross and other charity groups desig-nated by the crematories. Alternative Solutions has donated $45,000 so far, after a year in operation. Saadeh wants to increase that to $2 million annually as he works with more crematories—now at 160 nationwide. The number of people being cremated is up sharply and, sometime around 2020, crema-tions are expected for the first time to exceed burials nationwide, according to the Cremation Association of North America.

—BY (June 30, 2011)

Detecting Knee or Hip Replacement Infections

Infections that develop after total knee and hip arthroplasty are not always

easy to detect but are always serious complications. Infections can necessi-tate the complete removal of the implant and debridement of the surgical site. ECI Biotech, Inc., a developer of rapid infection diagnostics, has produced a 3D animation that describes how bio-film forms on orthopedic devices and features the company’s technology, ExpressDetect, to detect toxins secreted by those biofilms.

ECI Biotech, in conjunction with Cos-mocyte, developed the animation as a marketing tool to educate healthcare professionals about the problem of detecting bacteria in biofilms. Com-pany officials note that aspirations of synovial fluid and soft tissue biopsies often prove to be culture negative, mak-ing it difficult to distinguish these infec-tions from others.

Noting that there is a need for an accu-rate and rapid diagnostic for peripros-thetic joint infections, ECI Biotech officials believe that it has the research innovation to solve this problem with a Alternative Solutions USA, Inc.

large joints

Source: Wikimedia Commons and Mattes


VOLUME 7, ISSUE 22 | JULY 12, 201122rapid diagnostic that detects the pres-ence of toxins secreted by biofilms. The 3D animation of ECI’s technology is under clinical investigational use only and is not yet approved by the FDA. The video is being featured on Ortho-pedics This Week before it goes public on YouTube.

Mitch Sanders, Ph.D., CEO and found-er of the Worcester, Massachusetts firm, explains, “ECI hopes to commercialize this product with an industry leader in orthopedics. Social media and 3D ani-mations are great for sparking the inter-est of key opinion leaders. We partnered with Cosmocyte to produce this video. Cosmocyte did an incredible job at ren-dering the biofilms to produce a scien-tifically accurate and visually stimulat-ing animation that captivates viewers.”

—BY (July 6, 2011)

Deep Vein Thrombosis Drug Approved

The blood thinner Xarelto, produced by Janssen Pharmaceuticals, Inc., a

company of Johnson & Johnson and Bayer Health Care, has been approved by the FDA for the prevention of deep vein thrombosis (DVT) in patients who

had knee or hip replacement surgery per a July 1 press release. According to the company, about 80,000 patients in the U.S., the majority of whom are 55-years old or older and suffer from arthritis, undergo hip or knee replace-ment surgery every year. This cohort has a significantly higher risk of DVT.

DVT occurs when a blood clot develops in a large vein and blood circulation is blocked. If the clot becomes dislodged and travels along the bloodstream into the lungs, a potentially fatal condition, known as pulmonary embolism (PE) can develop. PE and DVT are the main reasons patients who had joint replace-ment surgery are re-hospitalized.

The American College of Chest Phy-sicians recommends that patients be given anticoagulants (blood thinners) after major orthopedic replacement surgery for up to 10 days following knee replacement and 35 days follow-ing hip replacement.

Human studies demonstrated Xarelto’s clinical benefits when it was compared to Lovenox (enoxaparin), the most widely used medication today. Xarel-to has been approved by regulatory authorities in over 100 countries for venous thromboembolism prevention in orthopedic replacement surgery.

—BY (July 6, 2011)

OMNIlife Makes Bold Knee Replacement Claim

OMNIlife science, Inc. has received FDA clearance for its Apex PS

Knee.

OMNIlife is a subsidiary of Orthopae-dic Synergy, Inc. a company led by for-mer Johnson & Johnson knee employ-ees, formed in late 2008 as a holding company for joint venture partners, Enztec, Ltd. of New Zealand, Praxim, SA of France and U.S.-based OMNIlife science.

The PS Knee was introduced into the European market at the end of 2010, with a full U.S. launch expected by the end of 2011.

A company announcement on July 5 said the PS “maintains the key design elements of the existing Apex Cruciate Retaining (CR) Knee but offers the post and cam system preferred by surgeons who utilize a posterior stabilized knee replacement.” The company believes the design allows the device to have up

Watc

h Video

Bayer Health Care/morgueFile

Apex PS Knee/OMNIlife, Inc.


VOLUME 7, ISSUE 22 | JULY 12, 201123to an additional 30° of uninterrupted patella track compared to competitive posterior stabilized knee designs that require a larger bone resection.

“The extra patella track potentially reduces the chance of experiencing a problem that has been associated with knee replacements known as patella ‘clunk’. A single-step reaming process allows a seamless intraoperative tran-sition from a CR Knee to a PS Knee based on surgeon preference. By taking advantage of the intercondylar fossa for the location of the Apex PS Knees’ ‘box’ cut, there is as much as a 90% reduction in the bone removed compared to some competitive PS Knee designs,” stated the company announcement.

Bold Claim

George Cipolletti, the company’s CEO and former manager, Knee Research at Johnson & Johnson, said, “We believe that the design of the Apex PS Knee will set a new standard in the orthopedic industry that will benefit both patients and surgeons.”

Anthony F. Infante, Jr., D.O. said, “I really enjoy using the instruments for the Apex PS knee; it’s certainly the easi-est and most repeatable box cut that I have ever made. In the past, I’ve typi-cally used an ultra congruent insert for posterior stabilization because of the amount of bone that was removed in a typical PS Knee. With the OMNI sys-tem, the amount of additional bone that is removed is so insignificant I have no problem using this PS Knee in all of my patients.”

Cipolletti’s claim is bold. Now surgeons and patients will have a chance to prove him right or wrong.

—WE (July 7, 2011)

Blueberries and Strong Bones

Get thee to a blueberry bush…New research from the Arkansas

Children’s Nutrition Center (ACNC) is showing that polyphenols in blueber-ries might just help us form strong, healthy bones—if, that is—results from studies with laboratory rats turn out to hold true for humans. This could hold promise for future treatments to boost development of bone mass and to help prevent osteoporosis.

Jin-Ran Chen, Ph.D. and his colleagues are exploring this idea in research fund-ed by the U.S. Department of Agricul-ture (USDA). Dr. Chen is a principal investigator and lead scientist at the center’s Skeletal Development Labora-tory, and an assistant professor in the

department of pediatrics at the Univer-sity of Arkansas for Medical Sciences, also in Little Rock.

Published in the Journal of Bone and Mineral Research in 2010, the investi-gation showed that animals fed rations that contained 10% freeze-dried blue-berry powder had significantly more bone mass than their counterparts whose rations were blueberry-free. When the researchers exposed labora-tory cultures of bone-forming cells to blood from the animals, the scientists found that serum from the blueberry-fed rats was associated with an increase in development of osteoblasts into mature, functional bone cells.

Serum in the blueberry-fed rats was high in phenolic acids, derived from the color-impacting polyphenols. The research suggests that the phenolic acids may have had bone-building effects in the rats.

Blueberries. Source: Wikimedia Commons and Famest

trauma


VOLUME 7, ISSUE 22 | JULY 12, 201124Dr. Chen told OTW,”Our study devel-oped from our interest in evidence about the role of nutrition in early development of bones, and, in particu-lar, the role of fruits and vegetables. It’s already known that proper nutrition during early development of our bones is essential for maximal accretion of bone mass, or what’s often referred to as ‘peak bone mass.’ And, it has been shown that intake of fruits and veg-etables by children during their early prepubertal years can be an indepen-dent predictor of their bone size. We wanted to expand upon this knowledge by developing more information about the bone-building effects of specific fruits and vegetables, such as—in this instance—blueberries.

Dr. Chen also commented to OTW, In our future studies, we want to determine whether the bone-building effect of blueberries, observed in laboratory rats, persists or is merely transitory. We also want to determine whether the effect significantly contributes to better bone health in later life. For example, we want to determine if consumption of blueber-ries during early bone development sig-nificantly reduces osteoporosis or bone fracture in adulthood. And, we want to determine whether there are novel bio-active compounds in blueberries that contribute significantly to bone health. These studies will likely be done with laboratory rats. After that, we’ll want to work with healthy volunteers to deter-mine if any of the bone building ben-efits that we document in the lab animal studies also occur in humans.

—EH (June 28, 2011)Advertisement

http://www.orthofix.com


VOLUME 7, ISSUE 22 | JULY 12, 201125Bone Loss: Mice in Space On July 8, 2011, researchers from the University of North Carolina at Chapel Hill/North Carolina State University Joint Department of Biomedical Engi-neering (UNC/NCSU) will be present for the final space shuttle launch of the NASA program as Atlantis departs for its final mission into Earth’s orbit. They will watch as 30 hairy little scientists—mice—accompany the astronauts into space. The goal? Discover new strate-gies to protect future astronauts from bone loss during extended exposure to micro-gravity.

The team is led by Ted Bateman, Ph.D., associate professor at UNC/NCSU with collaborators at the University of Colo-rado and Harvard.

In the July 6, 2011 news release, Dr. Bateman stated, “We’ve known for quite a while, since the 1970s and the Skylab

missions, that astronauts are going to lose bone on these extended missions. Comprehensive work has been done to identify the amount of loss—about one to two percent per month, which is approximately five times the rate that postmenopausal women lose bone here on Earth.”

“Though it has never been tested, we expect that during spaceflight, with the removal of gravitational loading, sclerostin levels will increase signifi-cantly,” Bateman added. “We believe this increase in sclerostin signal may be a primary reason why bone formation is reduced in astronauts and mice when they are in microgravity.”

In this experiment, half of the space-flown mice will be treated with a novel agent that blocks the activity of scleros-tin. This experimental agent, a scleros-tin antibody, has been shown to increase bone formation and bone mineral den-sity in ground-based mouse studies.

Dr. Bateman told OTW, “Launch is obviously the most interesting—and the biggest relief. It means the experi-ment has started and our logistics get much easier. But, later today we are choosing the 30 mice that will fly if launch is Friday. The mice have been here for nearly three weeks and we have been monitoring body mass and changes in growth. Yesterday we did bone density scans (DXA) on the mice. Based on body mass and DXA scans we choose the 30 that fly. And we choose Flight Group #2 if launch is delayed.”

Commenting to OTW on the type of treatment might this eventually lead for osteoporosis, Dr. Bateman stated, “The sclerostin antibody that we are testing on this mission, and that Amgen has in Phase I clinical trials, is a fundamentally different potential osteoporosis therapy. Unlike most of the osteoporosis thera-pies on the market now (that inhibit bone resorption, but do not build new bone), an antibody for sclerostin would

promote new bone formation. This would fill an important gap in osteoporosis treatment.”

“Scientifically, this drug is inter-esting because it is expressed by the cells within bone (osteo-cytes) that sense the stresses and strains that gravity imparts on the skeletal system. Absent grav-ity, sclerostin levels are expected to increase, so we are molecu-larly targeting the cause for bone loss very specifically (if the data fit our hypothesis).”

—EH (July 7, 2011)

Wikimedia Commons and NASA/Bill Engalls



Milliman Strikes at Lumbar Fusion in Florida

The Milliman Care Guidelines have reared their heads again over lum-

bar fusion. This time in Florida.

Citing, among other sources, the 2010 Milliman Guidelines for lumbar fusion, the Centers for Medicare and Medicaid Services (CMS) and Florida’s First Coast Service Options, Inc. have issued a policy draft with a Local Cov-erage Determination (LCD) that says Medicare will no longer cover multi-level lumbar fusion for symptomatic degenerative disc disease.

Specifically, the proposed policy states:

“Lumbar spinal fusion for the following conditions is not considered medically necessary and is noncovered:

1. When performed with initial pri-mary laminectomy/discectomy for

nerve root decompression or spi-nal stenosis, without documented spondylolisthesis

2. When performed with multiple-level (i.e., &GT;1 level) DDD”

We checked with NASS (North Ameri-can Spine Society), ISASS (Internation-al Society for the Advancement of Spine Surgery) and AANS (American Associa-tion of Neurological Surgeons) to see if the societies would band together again as they did in North Carolina when Blue Cross/Blue Shield issued a similar proposal last year. The societies are still evaluating the proposed language in the LCD and we would expect to hear soon if another unified front will take a stand in Florida.

Chris Bono, M.D., who co-authored the multi-society response in North Carolina, told OTW on June 30 that the Florida draft is less restrictive than the

original North Carolina proposal and offers additional pathways for coverage.

The comment period for the proposed policy expires July 13, 2011.

Comments can be sent to Medical Policy [email protected] Riverside AveROC 19TJacksonville, FL 32202

Draft LCDs are works in progress that are available on the Medicare Coverage Database site for public review. Draft LCDs are not necessarily a reflection of the current policies or practices of the contractor.

View the draft of the Local Cover-age Determination for Lumbar Spinal Fusion for Instability and Degenerative Disc Conditions (DL32074). —WE (June 30, 2011)

reimbursement

CMS



THE PICTURE OF SUCCESSDr. Ted Miclau, Part II

By Elizabeth Hofheinz, M.P.H., M.Ed.

Improbability is often the most pow-erful impetus to research. In the late

1800s, Dr. Joseph Lister used research to establish the improbable fact that infections are caused by unseen micro organisms. In the 1960s Dr. Marshall Urist demonstrated the improbable fact that a protein was the primary stimula-tor of bone growth. In the 1990s Dr. Arnold Caplan uncovered the improb-able fact that mesenchymal stem cells not only existed but were the immune privileged engine behind nerve, muscle and bone regeneration.

And finally, how improbable is it that a young child, raised in difficult finan-cial circumstances and enduring cul-tural challenges and familial disruption would graduate with honors from Yale University, study and excel as a resi-dent under Frank Wilson, M.D. at the University of North Carolina at Chapel Hill, author or co-author over 100 peer review articles, and become a tenured professor at the age of 40?

The answer is that it is well nigh impos-sible except that it is also a fact. When Dr. Ted Miclau assumes the reins of the pre-eminent Orthopaedic Research Society in 2012, he will bring to the position a unique set of passions and perspectives formed over 30 years of challenging ste-reotypes and achieving the improbable. While it is certainly true that orthope-dic research has come a long, long way over the past 40 years, it has not, how-ever, fully penetrated some of the poor-er corners of the world. Explains Dr. Miclau, “Many of my colleagues from Latin America tell me, ‘I can’t publish in the Journal of Bone and Joint Surgery.’ Not only are there language issues, but the fact is that at this point, many sur-geons don’t have the training to under-take the type of study designs that high quality journals expect. Working with one of the most accomplished orthope-dic clinical researchers in the world, Dr. Mohit Bhandari, I put together courses that teach orthopedists in Latin Amer-ica how to understand and design dif-

ferent clinical research methodologies and protocols. To date we have held these courses in Cuba and Mexico…I’m thrilled to say that they have been hugely successful.”

What Dr. Miclau and several colleagues from South America did was to attempt to examine the effectiveness of these courses by formulating pre- and post-tests that included a clinical scenario. “We asked participants things such as, ‘How would you develop a focused research question for this case, What techniques would you use to reduce

Dr. Ted MiclauPart I

I

Working with one of the most accomplished orthopedic clinical researchers in the world, Dr. Mohit Bhandari, I put together courses that teach orthopedists in Latin America how to understand and design different clinical research methodologies and protocols. To date we have held these courses in Cuba and Mexico…I’m thrilled to say that they have been hugely successful.

“

”



bias and confounding, or What should you consider when planning the sample size,’ The questionnaire also evaluated things such as what to consider when submitting a paper for publication and when to calculate sample sizes. As time goes on, we will continue to assess the impact that this type of course has had on surgeons’ ability to conduct research.”

Imagine if over one-third of orthope-dists in the U.S. came to your presen-tation and then said that they would alter clinical practice because of your talk. Dr. Miclau, who has affected the care of orthopedic patients for nearly an entire country, says, “A couple of years ago I taught in a clinical course in Paraguay—one that was attended by

more than a third of the orthopedic sur-geons in the country. Afterwards, over 90% of the audience indicated that they would change clinical practice because of what they had learned that day. That is just one bit of proof that training oth-ers to do things themselves is the most sustainable way of helping…and it is immeasurably satisfying.”

Dr. Miclau, a professor of orthopedics at the University of California, San Fran-cisco (UCSF), says that he hopes his legacy will be one of scientific advance-ment that changes the way orthope-dics is practiced or thought about. Dr. Miclau explains his vision: “In addition to our international work, I am proud to have created the foundation for a full-

service bench-to-bedside research pro-gram here at the Orthopaedic Trauma Institute, which includes a cellular and molecular biology lab, a biomechani-cal testing facility, a clinical research center, and a surgical training facility. The major focus of the Laboratory for Skeletal Regeneration is on the cellular and molecular events that occur dur-ing musculoskeletal injury and repair. In our biomechanics lab, we study the structural mechanisms behind and effective treatment for common ortho-pedic conditions. The clinical research center conducts outcomes research, including large multi-center national and international studies; we are also a core-center for METRC (Major Extrem-ity Trauma Research Consortium). In the surgical training facility we can compare the effectiveness of different surgical techniques using controlled, tissue-based research. Our research is now supported through competi-tive extramural funding, including the National Institutes of Health and the Department of Defense.”

Regarding his own research, Dr. Miclau says, “In one of my two R01 grants we are examining the effects of angiogen-esis and inflammation on bone healing from a cellular and molecular level. We were one of the first institutions to use a mouse tibia model, and have developed many different models that mimic rel-evant clinical situations. We use models for unstable fractures, intramedullary fixation, external fixation, and distrac-tion osteogenesis, among others. The two-fold goal is that these models will help us address different healing issues and be clinically relevant.”

During my time as president of the ORS, I hope to foster an environment that supports translational research opportunities. This includes developing a home for clinical researchers. “

”

Dr. Miclau (right) with faculty from Mexico, Cuba, Paraguay, Colombia, Brazil, Peru, and the U.S.


VOLUME 7, ISSUE 22 | JULY 12, 201129“My other R01 examines the role of muscle in bone repair. At the moment, we know that maintaining the soft tis-sue around a fracture is very impor-tant for healing and will decrease the chance of complications. Muscle has been thought to be a key soft tissue sur-rounding bone, but it’s not clear how much muscle contributes to healing through a contribution of cells or new blood vessels. One problem with work-ing with muscle is that the models for muscle injury are not very well devel-oped; we have had to develop animal models that give us an approach to and answers for these questions.”

Looking back, Dr. Miclau says that graduating from Yale is what he is most proud of. Looking forward, he says that his next role as president of the ORS will likely be the zenith of his career. Part of what led him to this summit is his work with the Orthopaedic Trauma Association (OTA). “I think my most substantial contributions to the OTA have been in the improvement of the way we evaluate research protocols, and the enhancement of basic science edu-cation. For example, when I chaired the OTA research committee we refined the way that the organization reviewed its research grants and worked to improve the quality of the grant applications through educational programs. When I took over as chair of the Basic Science Focus Forum, an event that is geared toward basic research topics that are clinically relevant to orthopedic trau-ma, our committee reorganized the way basic science was presented, and our level of participation has doubled—last year we had over 250 attendees.”

The next leader of the ORS has not only helped create the current research land-scape, he has a broad view of what is “out there.” “The exponential growth

of science has made it increasingly dif-ficult to manage the information ‘out there,’ making it particularly hard for individuals from different specialties to keep up-to-date. During my time as president of the ORS, I hope to foster an environment that supports translation-al research opportunities. This includes developing a home for clinical research-ers. Last year, I headed a group that organized a Clinical Research Forum at the ORS that addressed important issues in clinical research. This first-time symposium was sold-out and extremely well-received. My goal is to have this symposium grow as an annual event, that it would eventually become a place for clinical researchers to not only present their best clinical research papers, but also where they can assem-ble and network with each other and with basic researchers. This would be an ideal forum to discuss novel clinical

research themes ranging from new sta-tistical designs and subject recruitment strategies to how to organize research across different scientific disciplines.”

“Over the years, basic research in the musculoskeletal field has become increasingly sophisticated, which has had the effect of a divergence of research efforts. An example of this is clearly seen in biology, such that we have now have cartilage biologists, bone biolo-gists, stem cell biologists, etc. Getting all of these concerned parties, includ-ing biologists, engineers and clinicians together at the same meeting is impor-tant to ensure that we are working in close collaboration to achieve common goals and to advance the field.”

The surgeon who as a youth worked at nearly any job—from babysitting chick-ens to unloading cargo on the docks in

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VOLUME 7, ISSUE 22 | JULY 12, 201130Puerto Rico—tells younger surgeons, “work hard and manage your time.” “With the vast array of responsibilities I have taken on, it has been imperative that I develop good time management skills. While it may not sound like a revelation, ‘throwing hours’ at a prob-lem works, but people still need to be able to prioritize and develop an orga-nizational system that works for them.”

Dr. Miclau is realistic and honest. “Only you know what is most important to you. No matter what anyone says, prioritizing goals and areas of one’s life is difficult,

and may result in having to cut back time spent in another important area. If you say, ‘Patient care comes first…then my family,’ well, you may just feel some guilt about not spending enough time with your family. No matter what con-figuration of priorities I come up with, I pretty much spend my whole life feeling guilty about something!”

And then there is family. “My wife Kirsten and I have three children, ages 15, 13, and 10. All three children are national caliber divers and are involved in competitive soccer. I do my best to

make their sporting events, and work out myself when I can. We have all been involved with supporting local, inner-city youth soccer teams, composed largely of children from first-generation immigrant families, helping them to pay for their uniforms and equipment. This is something that has been espe-cially rewarding and a good life lesson for my children.”

Dr. Ted Miclau…thinking globally and acting everywhere. ◆



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