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What’s New in Primary Bone Tumors

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from studies cited in the December 17, 2014 Specialty Update on primary bone tumors:

Chondrosarcoma

–MicroRNA-145, an inhibitor of cell growth, was expressed at abnormally low levels in chondrosarcoma, lending credence to the hypothesis that underexpression of microRNA-145 plays a role in cancer development.

–Osteoclasts enhance the ability of chondrosarcoma to invade bone, but that invasion that can be partially halted by zoledronic acid.

–There is increased activity of the glycolysis-associated enzyme lactate dehydrogenase-A (LDHA) in chondrosarcoma.

–Density and location of new blood-vessel formation may be an important prognostic factor in chondrosarcoma.

–Conditional survival in patients with chondrosarcoma improves with each year of survival, but even patients who survive ten years after diagnosis cannot be considered cured.

Chordoma

–Variants of T transcription factor play a role in the pathophysiology of familial and sporadic chordoma.

–In patients with primary sarcomas of the spine, proton radiation plus surgery yielded local control rates of 85% at eight years.

Osteosarcoma

–Expression of the glucose transporter Glut-1 correlated with worse outcomes in patients with osteosarcoma.

–Secondary malignant neoplasms were found in 2.1% of long-term survivors of osteosarcoma.

–Use of fluorescence-guided surgery in a mouse model of osteosarcoma allowed reduction in the amount of residual tumor and improved disease-free survival.

–Among patients with high-grade osteosarcoma with soft-tissue extension, four parameters—tumor location, intracapsular extension, Huvos grade, and alkaline phosphatase level—may help predict which individuals will eventually develop metastases.

–In 45 patients with local recurrence but no metastases, the 10-year survival rate was 13%; most local recurrences were in soft tissue, not bone.

–Mid-therapy PET imaging may be useful to physicians in assessing response to chemotherapy.

Ewing Sarcoma

–Twenty-one percent of Ewing sarcoma samples had deletions of the STAG2 gene, and patients with STAG2 deletions had more aggressive tumors.

Soft-Tissue Sarcoma

–Among patients who also had surgery, intensity-modulated radiation therapy (IMRT) was associated with a lower local recurrence rate compared to conventional external-beam radiation.

–Six-month progression-free survival was 58% among 91 patients in a phase-II clinical trial of a hypoxia-activated cytotoxic agent (TH-302) used with doxorubicin.

–In a follow-up protocol comparison, radiography was noninferior to CT in terms of overall survival rate and disease-free survival.

–Ninety-five percent of 867 soft-tissue sarcoma patients who developed a recurrence did so within 8.6 years, raising questions about the usefulness of following patients beyond 10 years.

Reconstruction

–Due to high complication rates, intercalary allograft reconstruction after tumor resection should be reserved for defects of 15 cm or less, and plate-and-screw fixation should be used rather than intramedullary-nail fixation.

–Thirty-six patients who received frozen orthotopic autograft during reconstruction demonstrated a 10-year autograft survival rate of 80%.

–Patients who underwent pelvic reconstruction had a higher infection rate (26%), compared with those who did not undergo pelvic reconstruction (15%).

JBJS Classics: Correlating Lumbar MRIs with Clinical Findings

JBJS-Classics-logoEach month during the coming year, OrthoBuzz will bring you a current commentary on a “classic” article from The Journal of Bone & Joint Surgery. These articles have been selected by the Editor-in-Chief and Deputy Editors of The Journal because of their long-standing significance to the orthopaedic community and the many citations they receive in the literature. Our OrthoBuzz commentators will highlight the impact that these JBJS articles have had on the practice of orthopaedics. Please feel free to join the conversation about these classics by clicking on the “Leave a Comment” button in the box to the left.

In 1989, a group of sixty-seven asymptomatic individuals with no history of back pain or sciatica underwent magnetic resonance scans of the lumbar spine. In a landmark 1990 JBJS study, Boden et al. reported that three neuroradiologists who had no clinical knowledge of the patients interpreted the images as being substantially abnormal in 28% of the cohort (19 individuals). More specifically, a herniated nucleus pulposus was identified in 24 % of these asymptomatic subjects. These “magnetic-resonance positive” findings were more prevalent in older subjects; abnormal MRI findings were identified in 57% of those aged 60 to 80 years.

Boden et al. concluded that so many MRI findings of substantial abnormalities in asymptomatic people “emphasized the dangers of predicating a decision to operate on the basis of diagnostic tests—even when a state-of-the-art modality is used—without precise correlation with clinical signs and symptoms.”

However, despite the findings of Boden et al., during the last five years of the 1990s, Medicare claims showed a 40% increase in spine-surgery rates, a 70% increase in fusion-surgery rates, and a two-fold increase in use of spinal implants. Although spine-fusion surgery has a well-established role in treating certain spinal diseases, a 2007 systematic review of several randomized trials indicated that the benefits of fusion surgery were limited when treating degenerative lumbar discs with back pain alone. This review suggested the need for more thorough selection of surgical candidates, which was a caution also implied by Boden et al.

Although the three neuroradiologists in the Boden et al. study largely agreed on the absence or presence of abnormal findings on the MRIs, in 2014 Fu et al. reported on the interrater and intrarater agreements by four reviewers of MRI findings from the lumbar spine of 75 subjects. Even though this study used standardized evaluation criteria, there was significant variability in both interrater and intrarater agreement among the reviewers. As the Boden et al. study did 25 years ago, this study demonstrated the diagnostic limitations of MRI interpretation for lumbar spinal diseases.

In 2001, JBJS published a paper by Borenstein et al. that was a seven-year follow-up study among the same asymptomatic subjects studied by Boden et al. Borenstein et al. found that the original 1989 scans of the lumbar spine were not predictive of the future development or duration of low back pain. This led Borenstein et al. to conclude—as Boden et al. did—that “clinical correlation is essential to determine the importance of abnormalities on magnetic resonance images.”

Many important subsequent studies were inspired by the original findings of Boden et al. in JBJS. Most of them emphasize that for lumbar-spine diagnoses, an MRI is only one (albeit important) piece of data; that interpretation of MRIs is variable; and that all imaging information must be correlated to the specific patient’s clinical condition.

Several studies and national surveys indicate that approximately a quarter of US adults report having had back pain during the past 3 months, making this a common clinical complaint. But the findings of Boden, et al. and subsequent studies remind us that surgery is not always the appropriate treatment.

Daisuke Togawa, MD, PhD

JBJS Deputy Editor

Most Med Students to Sidestep Private Practice, but Ortho Residents Seek Independence

If you’re a physician in private practice, there may be very few doctors following in your footsteps, according to results from athenahealth’s 9th annual Epocrates Future Physicians of America Survey.

Among medical students who responded to the survey, 73% said they plan to seek employment through a hospital or large group practice; a mere 10% said they hope to join a private practice, down from 17% the previous year. One reason for the employed practice-setting preference: med students feel their training doesn’t prepare them for the challenges of running a business. Fifty-seven percent expressed dissatisfaction with their education in practice management, and 65% reported feeling unprepared for the exigencies of billing and coding.

When asked about their “top concerns,” 60% of respondents cited a desire for work-life balance as number one. That, along with an apparent aversion to the administrative hassles of private practice, helps explain this year’s findings.

However, when OrthoBuzz asked members of the JBJS Resident Advisory Board to comment on these findings, another side of the story emerged. Daniel Hatch, MD, a fifth-year resident at Penn State Hershey Orthopaedics, said, “I am a huge proponent of private-practice medicine and hope to join a private-practice group when I am done with training, but I too feel the pull toward employed positions with guaranteed high salaries for the first few years and large signing bonuses.  But I am looking for more autonomy and control in the decision-making related to my practice.”

Orrin Franko, MD, a chief resident at UC San Diego, concurred: “Personally, I desire the independence of private practice and do not fear the inevitable challenges I will face by running a business—but I am in the small minority,” he said.  “I have seen first-hand the personal satisfaction, financial success, and independence of private-practice surgeons, and I desire that for myself.  I hope that more of my colleagues feel the same way.  Otherwise, I feel we are at risk of losing control over our specialty to large hospital systems and payors.”

For Benjamin Service, MD, a resident at Orlando Health, the choice is “not simply academic versus private practice versus hospital employed…due to the variation in orthopedic practices.” Dr. Service agrees with the survey’s findings about subpar private-practice preparedness. “US medical schools are severely lacking in educating their students on debt management, finance, asset protection, and practice management,” he said.  “It is obvious that many students would not initially consider private practice due to this gap in our education.”

What do you think? Please let us know by clicking the “Leave a comment” button.

Revised JBJS LOE Table Improves Clinical Usefulness and Transparency

Since 2003, JBJS has assigned level-of-evidence (LOE) ratings to all clinical articles, based on a system developed by the UK’s Centre for Evidence-Based Medicine (CEBM). The CEBM updated its rating system in 2011, and The Journal has revised its LOE guidance in ways that largely but not entirely reflect the CEBM update.

In an editorial in the January 7, 2015 JBJS, Editor-in-Chief Dr. Marc Swiontkowski and Associate Editor for Evidence-Based Orthopaedics Dr. Robert Marx note that the revised JBJS LOE table still divides studies by type and that “much of the ranking criteria remain the same.” However, the rows and columns have been transposed and a column focused on specific clinical questions has been added. The clinical-question column—which poses queries such as “Does this treatment help?”—can guide busy clinicians quickly and efficiently to the best available evidence about their immediate situation.

In addition, guidance in the new table’s footnotes permits flexibility to grade studies upward if there is a dramatic effect size or downward on the basis of small effect size or study-quality issues such as imprecision. Overall, the revised table clarifies and makes more transparent The Journal’s LOE-assignment process.

Notably, The Journal has decided to depart from the CEBM update in two important ways. We will not follow the CEBM’s policy of reserving Level-I designation for systematic reviews, believing that certain high-quality original research also merits Level-I status. In addition, because economic and population-health decisions play an increasingly important role in orthopaedic surgery today, we have retained economic studies in our table, while the CEBM eliminated such research from its update.

Finally, the editorial reminds readers that “a higher LOE does not necessarily reflect the clinical importance of a given study.” Ultimately, each reader is responsible for deciding what constitutes the best external evidence for his or her specific clinical question.

Please let us know what you think about the revised LOE table by clicking the “Leave a comment” button.

“Fat Hormone” Associated with Cartilage Thinning

In a recent Annals of Rheumatic Diseases study, Australian researchers reported that levels of circulating leptin—a hormone that influences body weight and regulates some inflammatory processes—are negatively associated with changes in knee-cartilage thickness.

This prospective cohort study of 163 randomly selected patients (mean age of 63) used MRI to assess knee-cartilage thickness and radioimmunoassay to measure serum leptin levels at baseline and again after an average of 2.7 years. Cross-sectionally, leptin levels were negatively associated with cartilage thickness at femoral, medial tibial, lateral tibial, and patellar sites, after researchers adjusted for age, sex, BMI, and disease status. Longitudinally, baseline levels and changes in leptin over time were associated with greater differences in tibial-cartilage thickness.

The authors speculate that leptin may have a catabolic effect on cartilage that contributes to the development of osteoarthritis (OA), and that decreases in leptin levels associated with weight loss may help explain the clinical improvement in patients with knee OA who lose weight.

JBJS Supplement Cites New Findings from International Device Registries

Surgeons performed more than 1.1 million joint replacements in the US in 2011. That same year, the International Consortium of Orthopaedic Registries (ICOR) was launched to help close gaps in evidence and data collection related to orthopaedic implants. The ICOR network now consists of more than 70 stakeholders and more than 30 orthopaedic registries representing 14 nations.

The December 17, 2014 edition of The Journal contains an online supplement with 14 articles highlighting the achievements of international registries and the findings from 12 ICOR-initiated registry studies. The first article in the supplement (National and International Postmarket Research and Surveillance Implementation) summarizes the findings from the 12 registry studies. The second article (A Distributed Health Data Network Analysis of Survival Outcomes) provides an overview of the data extraction processes and analytic strategies used in the studies.

Key findings from the 12 studies contained in the supplement:

There were no differences in revision risk when metal-on-HXLPE (highly cross-linked polyethylene) implants with larger and smaller femoral head sizes were compared.

Non-cross-linked polyethylene was not associated with significantly worse revision outcomes when compared with metal-on-HXLPE.

Large-head-size metal-on-metal implants were associated with increased risk of revision after two years, compared with metal-on-HXLPE implants.

Use of ceramic-on-ceramic implants with a smaller head size was associated with a higher revision risk compared with metal-on-HXLPE implants and ceramic-on-ceramic implants with head sizes >28 mm.

When compared with hybrid fixation, cementless fixation was associated with an approximately 58% higher risk of revision surgery in patients aged 75 years or older.

Mobile-bearing, non-posterior-stabilized knee designs presented a 40% higher risk of failure than that found with fixed-bearing, non-posterior-stabilized designs.

Compared with fixed-bearing posterior-stabilized knee prostheses, patients who received mobile bearings had an 85% higher chance of revision within the first postoperative year.

Fixed non-posterior-stabilized (cruciate-retainin0 TKA performed better (with or without patellar resurfacing) than did fixed posterior-stabilized (cruciate-substituting) TKA.

Reported revision rates of TKA and THA among pediatric and young-adult patients is currently similar to that for older patients, but the dearth of data makes it incumbent on registries to continue collecting and analyzing data relevant to younger populations.

This systematic review and meta-analysis concluded that surgeons performing a primary THA should use an implant that outperforms benchmarks established by the UK’s National Institute for Health and Care Excellence (NICE).

Among 19 registry reports and 1052 articles examined, only one report and two studies mentioned patient-reported outcome measures (PROMs) and minimum clinically important differences in connection with revision rates after TKA or THA.

Successful collection of PROM data is possible with careful attention to selection of outcome measure(s) and minimizing the data-collection burden on physicians and patients.

Publisher’s Note: Launch of PRE-val supports “Excellence Through Peer Review”

A year ago we debuted the “peer-review statement” in The Journal to emphasize our commitment to pre-publication peer review and to the rigorous, double-blind peer-review process that is integral to our editorial standards.

Today we are happy to announce our participation in PRE-val, the flagship service offered by PRE (Peer Review Evaluation). Our readers will notice the PRE-val badge above the article title for most JBJS articles published on our website in the past 12 months. Clicking on the badge reveals the PRE-val window, which provides detail about the peer review for that particular article. We know that your confidence in the reliability of the information published in The Journal will be increased by the enhanced transparency of our peer-review process.

As a result of the commitment to peer review shared by JBJS and PRE, our Board of Trustees approved the acquisition of PRE in 2014. We are excited about this launch, and we look forward to the implementation of this valuable service on the sites of our partner publishers over the coming months. You can learn more about PRE here. Of course, we welcome your feedback; please let us know what you think of this initiative by writing to us at info@jbjs.org.

Medical publishing continues to evolve-sometimes to keep up with technology, sometimes due to financial constraints, and, unfortunately, sometimes in ways that make some of us uncomfortable-but readers of JBJS can be assured that our commitment to peer review and the quality it helps us to achieve will not waver. “Excellence Through Peer Review” will always remain a critical element of our core mission.

–Mady Tissenbaum, Publisher, JBJS

JUPITER Says Statins Don’t Deliver Fracture Benefit

When it comes to heart disease and stroke, statins are remarkably effective drugs, and some observational studies have suggested that these lipid-lowering medications might even reduce the risk of bone fractures. But a secondary analysis of the JUPITER trial—a randomized study designed primarily to determine whether rosuvastatin (Crestor) had any effect on cardiovascular outcomes in people who were not candidates for statins—found that statin therapy did not reduce fracture risk. The study population included more than 17,800 men and women with a mean age of 66.

The JUPITER trial was halted after less than two years because of the significant cardiovascular benefits seen in the Crestor group. During that 1.9-year period, 221 imaging-confirmed fractures occurred in the Crestor group, while 210 fractures occurred in the placebo group, according to a paper published online in JAMA Internal Medicine. This fracture-focused secondary analysis was prespecified before the trial started, not run as an afterthought, which adds credibility to the findings.

Online Patient Self-Scheduling Could Save Time and Money

A new report from Accenture estimates that by 2019, two-thirds of US health systems will offer patients the opportunity to digitally self-schedule physician appointments. By reducing the time spent scheduling and rescheduling (an average of 8 minutes per phone appointment versus less than a minute for online self-scheduling), this simple change could save the health care system an estimated $3.2 billion.

Accenture says that nationwide, 11% of health systems currently offer self-scheduling of appointments, but only 2.4% of patients who have the opportunity take advantage of it. That may be partly because retirees—a population that generally prefers conducting business by phone—make up nearly half of the US population. Still, a recent Accenture survey indicated that 77% of patients thought that the ability to book, change, or cancel medical appointments online was important.

JBJS Classics: Periprosthetic Bone Loss in Total Hip Arthroplasty

JBJS-Classics-logoEach month during the coming year, OrthoBuzz will bring you a current commentary on a “classic” article from The Journal of Bone & Joint Surgery. These articles have been selected by the Editor-in-Chief and Deputy Editors of The Journal because of their long-standing significance to the orthopaedic community and the many citations they receive in the literature. Our OrthoBuzz commentators will highlight the impact that these JBJS articles have had on the practice of orthopaedics. Please feel free to join the conversation about these classics by clicking on the “Leave a Comment” button in the box to the left.

This classic investigation on periprosthetic bone loss (J Bone Joint Surg Am 1992; 74:849–863) was conducted by Tom Schmalzried in the early 1990s working in William Harris’ laboratory.  Specimens from osteolytic lesions both near and far from the articular surface in 34 total hip arthroplasties were studied by plain and polarized light microscopy, as well as transmission electron microscopy.

The authors emphasized the role of activated macrophages containing micron and submicron polyethylene particles in the bone resorption evident in the areas of osteolysis.  They speculated that the polyethylene-laden joint fluid migrated and penetrated far from the bearing surface to the points of least resistance.  Thus, the concept of an effective joint space (i.e., all periprosthetic regions that are accessible to joint fluid and its particulate debris by the pumping action of the joint) was introduced into the orthopaedic lexicon.

Although the findings identified in this study were not necessarily new, the insights proffered by the authors radically altered our thoughts about osteolysis.  Using this concept of effective joint space, subsequent investigators and innovators identified methods and designs of hip replacements to retard osteolysis by limiting the generation and spread of particulate debris.

Thus, the 1990s were marked by the development of solid acetabular cups, nonmodular monoblock components, improved liner locking mechanisms to avoid backside wear, circumferentially coated femoral stems, highly crossed-linked polyethylene to lessen abrasive wear, and metal and ceramic bearing surfaces.  As appreciated by most orthopaedic residents, the article also led to a generation of questions on the Orthopaedics In-Training Exam (OITE) about the importance of macrophages in the pathogenesis of osteolysis.

Recently, some investigators speculate on a more significant mechanical effect of metal-on-metal joint fluid in causing the pseudotumors and muscle damage/necrosis that is frequently evident.  Regardless of whether the primary effect of small particle-laden joint fluid is biologic or mechanical, I believe that the theory of effective joint space remains a valid anatomic concept for all arthroplasty surgeons.

Robert Bucholz, MD

JBJS Deputy Editor for Adult Reconstruction and Trauma