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Nontraumatic Osteonecrosis: An Early Target for Gene Therapy

As osteonecrosis of the femoral head (ONFH) progresses, it can impair a patient’s ability to walk, and hip arthroplasty is often the only effective long-term option. Other interventions to relieve the pain of ONFH include surgical decompression of the femoral head, which is generally effective but often does not change the natural history of the process. Once the femoral head collapses and loses sphericity, degenerative arthritis of the hip follows quickly. Well-documented risk factors for ONFH include excessive alcohol consumption and corticosteroid use. But why do some patients with these risk factors develop osteonecrosis, while others do not.

In the September 16, 2020 issue of The Journal, Zhang et al. address that clinical quandary with a genomewide association study on a chart-reviewed cohort of 118 patients with ONFH and >56,000 controls. The findings shed light on what is obviously a condition with multifactorial etiology and complex gene-environment interactions. The case-control study identified 1 gene (PPARGC1B) and 4 single nucleotide variants associated with ONFH overall, and with 2 subgroups—those exposed to corticosteroids and those with femoral head collapse. Steroid intake was highly prevalent in both cohorts—90.7% of the ONFH patients had at least one 3-week course of corticosteroids, compared with 68.3% of controls.

For readers interested in the detailed genetic bases for osteonecrosis, this study offers a treasure trove of data. But for all of us, these findings, after they are verified in other populations, may very well form the basis for pharmacologic and gene-modifying strategies in patients at risk for ONFH. Moreover, osteonecrosis of the femoral head is just one of many musculoskeletal conditions that can probably be addressed with this type of genome-based research strategy.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

Treating Developmental Hip Dislocations Diagnosed after Walking Age

There is a wry saying in academic medicine that “nothing ruins good results like long-term follow-up.” But long-term follow-up helps us truly understand how our orthopaedic interventions affect patients. This is especially important with procedures on children, and the orthopaedic surgeons at the University of Iowa have been masterful with long-term outcome analysis in pediatric orthopaedics. They demonstrate that again in the August 5, 2020 issue of The Journal, as Scott et al. present their results comparing outcomes among 2 cohorts of patients who underwent treatment for developmental hip dislocations between the ages of 18 months and 5 years—and who were followed for a minimum of 40 years.

Seventy-eight hips in 58 patients underwent open reduction with Salter innominate osteotomy, and 58 hips in 45 patients were treated with closed reduction. At 48 years after reduction, 29 (50%) of the hips in the closed reduction cohort had undergone total hip arthroplasty (THA), compared to 24 (31%) of hips in the open reduction + osteotomy group. This rate of progression to THA nearly doubled compared to previously reported results at 40 years of follow-up, when 29% of hips in the closed reduction group and 14% of hips in the open reduction group had been replaced.

In addition, the authors found that patient age at the time of reduction and presence of unilateral or bilateral disease affected outcomes. Patients with bilateral disease who were treated at 18 months of age had a much lower rate of progression to THA when treated with closed reduction, compared to those treated with open reduction—but the opposite was true among patients with bilateral disease treated at 36 months of age. Treatment type and age did not seem to substantially affect hip survival among those with unilateral disease.

I commend the authors for their dedication to analyzing truly long-term follow-up data to help us understand treatment outcomes among late-diagnosed developmental hip dislocations in kids. Long-term follow-up may “ruin” good results, but it gives us more accurate and useful results. And, in this case, the findings reminded us how important it is to diagnose and treat developmental hip dislocations as early in a child’s life as possible.

Read the JBJS Clinical Summary about this topic.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Less Drinking/Smoking Associated with Fewer Hip Fractures

OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Shahriar Rahman, MS in response to a recent study in JAMA Internal Medicine.

Hip fractures are an important cause of morbidity and mortality among the elderly population worldwide. However, age-adjusted hip fracture incidence has decreased in the US over the last 2 decades. While many attribute the decline to improved osteoporosis treatment, the definitive cause remains unknown. A population-based cohort study of participants in the Framingham Heart Study prospectively followed a cohort of >10,000 patients for the first hip fracture between 1970 and 2010.

The age-adjusted incidence of hip fracture decreased by 4.4% per year during this study period. That decrease in hip fracture incidence was coincident with a decrease over those same 4 decades in rates of smoking (from 38% in 1970 to 15% by 2010) and heavy drinking (from 7% to 4.5%), with subjects born more recently having a lower incidence of hip fracture for a given age. Meanwhile, during the study period, the prevalence of other hip-fracture risk factors–such as being underweight, being obese, and experiencing early menopause–remained stable.

This study’s findings should be interpreted in light of 2 major limitations. First of all, there was a lack of contemporaneous bone mineral density data across the study period; secondly, all the study subjects were white. Nevertheless, these findings should encourage physicians to continue carefully managing patients who have osteoporosis and at the same time caution them against smoking and heavy drinking.

Shahriar Rahman, MS is an assistant professor of orthopaedics and traumatology at the Dhaka Medical College and Hospital in Bangladesh and a member of the JBJS Social Media Advisory Board.

What’s New in Musculoskeletal Infection 2020

Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz specialty-update summaries.

This month, Thomas K. Fehring, MD, co-author of the July 15, 2020 What’s New in Musculoskeletal Infection,” selected the five most clinically compelling findings—all focused on periprosthetic joint infection (PJI)—from among the more than 80 noteworthy studies summarized in the article.

PJI Prevention
–A retrospective case-control study1 found that patients who received an allogeneic blood transfusion during or after knee or hip replacement had a higher risk of PJI than those who were not transfused.

PJI Diagnosis
–A retrospective review2 found that using inflammatory markers to diagnose PJI in immunosuppressed joint-replacement patients is not suitable and that newly described thresholds for synovial cell count and differential have better operative characteristics.

Treating PJI
–A retrospective review3 of a 2-stage debridement protocol with component retention in 83 joint-replacement patients showed an 86.7% success rate of infection control at an average follow-up of 41 months.

–A single-center study4 of perioperative antibiotic selection for patients undergoing total joint arthroplasty found that the risk of PJI was 32% lower among those who received cefazolin compared with those who received other antimicrobial agents. The findings emphasize the importance of preoperative allergy testing in patients with stated beta-lactam allergies.

–A review of regional and state antibiograms5 showed that 75% of methicillin-sensitive S. aureus (MSSA) isolates and 60% of both methicillin-resistant S. aureus (MRSA) and coagulase-negative Staphylococcus isolates were susceptible to clindamycin, whereas 99% of all isolates were susceptible to vancomycin.

References

  1. Taneja A, El-Bakoury A, Khong H, Railton P, Sharma R, Johnston KD, Puloski S, Smith C, Powell J. Association between allogeneic blood transfusion and wound infection after total hip or knee arthroplasty: a retrospective case-control study. J Bone Jt Infect. 2019 Apr 20;4(2):99-105.
  2. Lazarides AL, Vovos TJ, Reddy GB, Kildow BJ, Wellman SS, Jiranek WA, Seyler TM. Traditional laboratory markers hold low diagnostic utility for immunosuppressed patients with periprosthetic joint infections. J Arthroplasty.2019 Jul;34(7):1441-5. Epub 2019 Mar 12.
  3. Chung AS, Niesen MC, Graber TJ, Schwartz AJ, Beauchamp CP, Clarke HD, Spangehl MJ. Two-stage debridement with prosthesis retention for acute periprosthetic joint infections. J Arthroplasty.2019 Jun;34(6):1207-13. Epub 2019 Feb 16.
  4. Wyles CC, Hevesi M, Osmon DR, Park MA, Habermann EB, Lewallen DG, Berry DJ, Sierra RJ. 2019 John Charnley Award: Increased risk of prosthetic joint infection following primary total knee and hip arthroplasty with the use of alternative antibiotics to cefazolin: the value of allergy testing for antibiotic prophylaxis. Bone Joint J.2019 Jun;101-B(6_Supple_B):9-15.
  5. Nodzo SR, Boyle KK, Frisch NB. Nationwide organism susceptibility patterns to common preoperative prophylactic antibiotics: what are we covering? J Arthroplasty.2019 Jul;34(7S):S302-6. Epub 2019 Jan 17.

Complex Reconstructions Call for Creative Solutions

Metastatic disease around the acetabulum often leads to patients needing total hip arthroplasty (THA), plus supplementary acetabular reconstruction. Traditional methods such as the Harrington reconstruction technique have shown good short-term outcomes, but there are concerns that a cemented acetabular component in this setting is at risk for failure in the longer term. Newer approaches, such as using cementless tantalum acetabular components with augments, have also shown promise. Houdek et al. compared these 2 approaches and report the findings in the July 15, 2020 issue of The Journal.

The authors followed 115 patients who underwent THA for metastatic disease at 2 tertiary sarcoma centers, with a mean 4-year follow-up among surviving patients. They compared the outcomes of 78 Harrington reconstructions with those of 37 tantalum reconstructions, with surgeons at each center exclusively performing 1 of the 2 techniques. The cohorts were comparable at baseline regarding age, sex, severity of systemic disease and acetabular defects, and pelvic discontinuity. Functional outcomes improved in both groups, but there were no significant between-group differences. The main statistical finding of the study was that a higher percentage of patients in the Harrington reconstruction group (27%) needed a reoperation than those in the tantalum group (8%), with a hazard ratio of 4.59 (p=0.003).

Historically, there has been an understandable lack of long-term follow-up in this fragile patient population; 94 of the 115 patients in this study died of systemic disease progression at an average of 16 months after surgery. Overall patient survival was only 34% at 2 years and 15% at 10 years. Despite these grim mortality numbers, Houdek et al. claim that with advances in treatments for metastatic cancer, patients are living longer and therefore may benefit from more durable acetabular reconstructions.

This study leaves unanswered the question of whether the theoretic advantage of bony ingrowth with tantalum is what accounted for the decreased reoperation rates. As Albert Aboulafia, MD notes in his Commentary on this study, the authors did not review radiographs or postmortem histology to look for evidence of osseointegration. But Houdek et al. do present a potential avenue for further investigation. And what remains clear is that metastatic disease around the hip is a complex problem, and that we as surgeons should continue to investigate promising treatment strategies to improve patient outcomes (even if only palliative) and enhance biological fixation.

Click here for a 4-minute video in which co-author Matthew Houdek explains the rationale for this study.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Questions About Survival of Ultraporous Cups in THA

Acetabular components for primary total hip arthroplasty (THA) made with ultraporous surfaces were developed to enhance osseointegration and biological fixation. In the July 1, 2020 issue of The Journal of Bone & Joint Surgery, Palomaki et al. report on a registry study that suggests that implant survival with these components over an average follow-up of 3.6 years is not so “ultra.”

The authors evaluated >6,000 primary THAs that used a Tritanium ultraporous cup and >25,000 THAs that used a conventional cup, all performed between 2009 and 2017. When they compared the two groups for revision for any reason, the 5-year Kaplan-Meier survivorship of the Tritanium group (94.7%) was inferior to that of the conventional-cup group (96.0%). When revision for aseptic loosening was examined, the 5-year survivorship was also inferior for the Tritanium group (99.0%) compared with the conventional group (99.9%). Regression analysis revealed that the Tritanium group had a much higher risk of revision for aseptic loosening 2 to 4 years after surgery (hazard ratio, 11.2; p <0.001). Interestingly, these survivorship and risk-of-revision differences disappeared when the authors analyzed data for the period from May 15, 2014 to December 31, 2017–when the registry was updated to include patient BMI and ASA-class data.

The authors cite several caveats that readers should apply to these findings. The registry did not capture radiographic findings for these patients, so potentially relevant imaging data could not be analyzed. And, despite the database upgrade in 2014, there was a dearth of available data on patient comorbidities. Finally, wide confidence intervals for some of the hazard-ratio calculations suggest the need to confirm revision-risk findings with further research.

Limitations notwithstanding, the study by Palomaki et al. suggests that the performance of ultraporous cups may not meet the hopes and expectations of hip surgeons and their patients.

What’s New in Orthopaedic Trauma 2020

Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of OrthoBuzz summaries of these “What’s New” articles. This month, co-author Niloofar Dehghan, MD, selected the 5 most clinically compelling findings from the >20 studies summarized in the July 1, 2020 “What’s New in Orthopaedic Trauma.

Hip Fracture
—An international randomized controlled trial (RCT) of hip fracture patients ≥45 years of age1 compared outcomes among 1,487 who underwent an “accelerated” surgical procedure (within 6 hours of diagnosis) and 1,483 who received “standard care” (surgery within 24 hours of diagnosis). Mortality and major complication percentages were similar in both groups, but it is important to note that even the standard-care group had a relatively rapid median time-to-surgery of 24 hours.

—An RCT of nearly 1,500 patients who were ≥50 years of age and followed for 2 years2 compared total hip arthroplasty (THA) with hemiarthroplasty for the treatment of displaced femoral neck fractures. There was no between-group difference in the need for secondary surgical procedures, but hip instability or dislocation occurred in 4.7% of the THA group versus 2.4% of the hemiarthroplasty group. Functional outcomes measured with the WOMAC index were slightly better (statistically, but not clinically) in the THA group. Serious adverse events were high in both groups (41.8% in the THA group and 36.7% in the hemiarthroplasty group). Although the authors conclude that the advantages of THA may not be as compelling as has been purported, THA’s benefits may become more pronounced with follow-up >2 years.

—A preplanned secondary analysis of data from the FAITH RCT examined the effect of posterior tilt on the need for subsequent arthroplasty among older patients with a Garden I or II femoral neck fracture who were treated with either a sliding hip screw or cannulated screws. Patients with a posterior tilt of ≥20° had a significantly higher risk of subsequent arthroplasty (22.4%) compared with those with a posterior tilt of <20° (11.9%). In light of these findings, instead of internal fixation, primary arthroplasty may be an appropriate treatment for older patients who have Garden I and II femoral neck fractures with posterior tilt of >20°.

Ankle Syndesmotic Injury
—An RCT that compared ankle syndesmosis fixation using a suture button with fixation using two 3.5-mm screws3 found a higher rate of malreduction at 3 months postoperatively with screw fixation (39%) than with suture button repair (15%). With the rate of reoperation also higher in the screw group due to implant removal, these findings add to the preponderance of recent evidence that the suture button technique is preferred.

Wound Management
—A 460-patient RCT examining the cost-effectiveness of negative-pressure wound therapy4 for initial wound management in severe open fractures of the lower extremity found the technique to  be associated with higher costs and only marginal improvement in quality-adjusted life-years for patients.

References

  1. HIP ATTACK Investigators. Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial. Lancet.2020 Feb 29;395(10225):698-708. Epub 2020 Feb 9.
  2. Bhandari M, Einhorn TA, Guyatt G, Schemitsch EH, Zura RD, Sprague S, Frihagen F, Guerra-Farfán E, Kleinlugtenbelt YV, Poolman RW, Rangan A, Bzovsky S, Heels-Ansdell D, Thabane L, Walter SD, Devereaux PJ; HEALTH Investigators. Total hip arthroplasty or hemiarthroplasty for hip fracture. N Engl J Med.2019 Dec 5;381(23):2199-208. Epub 2019 Sep 26.
  3. Sanders D, Schneider P, Taylor M, Tieszer C, Lawendy AR; Canadian Orthopaedic Trauma Society. Improved reduction of the tibiofibular syndesmosis with TightRope compared with screw fixation: results of a randomized controlled study. J Orthop Trauma.2019 Nov;33(11):531-7.
  4. Petrou S, Parker B, Masters J, Achten J, Bruce J, Lamb SE, Parsons N, Costa ML; WOLLF Trial Collaborators. Cost-effectiveness of negative-pressure wound therapy in adults with severe open fractures of the lower limb: evidence from the WOLLF randomized controlled trial. Bone Joint J.2019 Nov;101-B(11):1392-401.

Patients as Teachers: Surgeons as Students

In the July 1, 2020 issue of The Journal, Dr. C. McCollister Evarts, writes an illuminating “What’s Important” essay about learning from his most difficult cases. He recounts an event early in his career as a medical officer aboard an aircraft carrier, when a fat embolism caused the untimely death of a young adult patient he treated for a closed tibial fracture. This event spurred a lifelong quest for knowledge about surgery-associated emboli, about which cases and literature were sparse at the time (mid-1960s). My quick search of Dr. Evarts’ long list of publications shows that more than 20 of them are related to embolic events, no doubt a direct result of the experience with that seaman many years ago, and with another one of his early-career patients who died of a pulmonary embolism a week after undergoing hip surgery.

We should all look toward our patients to teach us ways to improve our craft. Not every procedure goes as planned, and the day a surgeon stops trying to get better should likely be the day he or she starts contemplating retirement. Dr. Evarts states that “each and every encountered complication should be carefully examined with the goal of ultimately providing better care.”

Instead of fearing complications, orthopaedic surgeons should carefully analyze the root causes of complications as part of their career-long effort to learn and improve. Our patients can be our teachers in these difficult situations, and we should be willing and open students. This teacher-student approach might require a difficult conversation with the patient or their family to understand why the procedure didn’t go as planned or the outcomes weren’t what was envisioned. As Dr. Evarts points out in his essay, “Most family members do not understand what has happened when a complication occurs, and they appreciate an explanation in a face-to-face meeting.”

The adage that “you learn something new every day” is more likely to come true if you pay extra attention to your most difficult cases. As practicing surgeons, we are never “finished.” We should strive to remain teachable students, always learning from our patient-teachers.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Predictors of Prolonged Analgesic Use after Joint Replacement

OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Eric Secrist, MD in response to a recent study in Arthritis Research & Therapy.

There has been a proliferation of research regarding postoperative opioid usage after joint arthroplasty due to the widespread opioid epidemic. But Rajamäki and colleagues from Tampere University in Finland took the unique approach of also analyzing acetaminophen and NSAID usage in addition to opioids. The authors used robust data from Finland’s nationwide Drug Prescription Register, which contains reliable information on all medications dispensed from pharmacies, including over-the-counter drugs.

After excluding patients who underwent revision surgery or had their knee or hip replaced for a diagnosis other than osteoarthritis, the authors analyzed 6,238 hip replacements in 5,657 patients and 7,501 knee replacements in 6,791 patients, all performed between 2002 and 2013. The mean patient age was 68.7 years and the mean BMI was 29.

One year postoperatively, 26.1% of patients were still filling prescriptions for one or more analgesics, including NSAIDs (15.5%), acetaminophen (10.1%), and opioids (6.7%). Obesity and preoperative analgesic use were the strongest predictors of prolonged analgesic medication usage 1 year following total joint arthroplasty. Other predictors of ongoing analgesic usage included older age, female gender, and higher number of comorbidities. Patients who underwent knee replacement used the 3 analgesics more often than those who underwent hip replacement.

This study had all of the limitations inherent in retrospective database analyses. Additionally, it was not possible for the authors to determine whether patients took analgesic medications for postoperative knee or hip pain or for pain elsewhere in their body. Finally, the authors utilized antidepressant reimbursement data as a surrogate marker for depression and other medications as a surrogate for a Charlson Comorbidity Index.

Figure 2 from this study (shown below) reveals 2 important findings. First, total joint arthroplasty resulted in a significant decrease in the proportion of patients taking an analgesic medication, regardless of BMI. Second, patients in lower BMI categories were less likely to use analgesics both preoperatively and postoperatively.

The findings from this study may be most useful during preoperative counseling for obese patients, who often present with severe joint pain but are frequently told they need to delay surgery to lose weight and improve their complication-risk profile. Based on this study, those patients can be counseled that losing weight will not only decrease their complication risk, but also decrease their reliance on medications for the pain that led them to seek surgery in the first place.

Eric Secrist, MD is a fourth-year orthopaedic resident at Atrium Health in Charlotte, North Carolina.

July 2020 Article Exchange with JOSPT

For the last 6 years, JBJS has participated in an “article exchange” collaboration with the Journal of Orthopaedic & Sports Physical Therapy (JOSPT) to support multidisciplinary integration, continuity of care, and excellent patient outcomes in orthopaedics and sports medicine.

During the month of July 2020, JBJS and OrthoBuzz readers will have open access to the JOSPT systematic review and meta-analysis titled “Effectiveness of Weight-Loss Interventions for Reducing Pain and Disability in People with Common Musculoskeletal Disorders.”

The authors found low-credibility evidence that behavioral weight-loss interventions produced small to moderate improvements in pain intensity and disability in people with hip or knee osteoarthritis. They also found moderate-credibility evidence that combined diet and exercise weight-loss strategies improved pain intensity and disability compared to diet-only interventions for knee osteoarthritis.